Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Clinical Pharmacokinetics
Erschienen in: Clinical Pharmacokinetics 12/2001

01.12.2001 | Review Articles

Delivery of Neurotrophic Factors to the Central Nervous System

Pharmacokinetic Considerations

verfasst von: Robert G. Thorne, Dr William H. Frey II

Erschienen in: Clinical Pharmacokinetics | Ausgabe 12/2001

Einloggen, um Zugang zu erhalten

Abstract

Neurotrophic factors are proteins with considerable potential in the treatment of central nervous system (CNS) diseases and traumatic injuries. However, a significant challenge to their clinical use is the difficulty associated with delivering these proteins to the CNS. Neurotrophic factors are hydrophilic, typically basic, monomeric or dimeric proteins, mostly in the size range of 5 to 30 kDa. Neurotrophic factors potently support the development, growth and survival of neurons, eliciting biological effects at concentrations in the nanomolar to femtomolar range. They are not orally bioavailable and the blood-brain and blood-cerebrospinal fluid barriers severely limit their ability to enter into and act on sites in the CNS following parenteral systemic routes of administration. Most neurotrophic factors have short in vivo half-lives and poor pharmacokinetic profiles. Their access to the CNS is restricted by rapid enzymatic inactivation, multiple clearance processes, potential immunogenicity and sequestration by binding proteins and other components of the blood and peripheral tissues.
The development of targeted drug delivery strategies for neurotrophic factors will probably determine their clinical effectiveness for CNS conditions. Achieving significant CNS target site concentrations while limiting systemic exposure and distribution to peripheral sites of action will lessen unwanted pleiotropic effects and toxicity.
Local introduction of neurotrophic factors into the CNS intraparenchymally by direct injection/infusion or by implantation of delivery vectors such as polymer matrices or genetically modified cells yields the highest degree of targeting, but is limited by diffusion restrictions and invasiveness. Delivery of neurotrophic factors into the cerebrospinal fluid (CSF) following intracerebroventricular or intrathecal administration is less invasive and allows access to a much wider area of the CNS through CSF circulation pathways. However, diffusional and cellular barriers to penetration into surrounding CNS tissue and significant clearance of CSF into the venous and lymphatic circulation are also limiting. Unconventional delivery strategies such as intranasal administration may offer some degree of CNS targeting with minimal invasiveness.
This review presents a summary of the neurotrophic factors and their indications for CNS disorders, their physicochemical characteristics and the different approaches that have been attempted or suggested for their delivery to the CNS. Future directions for further research such as the potential for CNS disease treatment utilising combinations of neurotrophic factors, displacement strategies, small molecule mimetics, chimaeric molecules and gene therapy are also discussed.
Literatur
1.
2.
Hefti F, Denton TL, Knusel B, et al. Neurotrophic factors: What are they and what are they doing? In: Loughlin SE, Fallon JH, editors. Neurotrophic factors. San Diego (CA): Academic Press, Inc., 1993: 25–49
3.
Landreth GE. Growth factors. In: Siegel GJ, editor. Basic neurochemistry: molecular, cellular and medical aspects. 6th ed. Philadelphia (PA): Lippincott-Raven, 1999: 383–98
4.
5.
Cohen S, Levi-Montalcini R, Hamburger V. A nerve growth-stimulating factor isolated from sarcomas 37 and 180. Proc Natl Acad Sci U S A 1954; 40: 1014–8PubMedCrossRef
6.
Saragovi HU, Gehring K. Development of pharmacological agents for targeting neurotrophins and their receptors. Trends Pharmacol Sci 2000; 21: 93–8PubMedCrossRef
7.
Broadwell RD, Banks WA. Cell biological perspective for the transcytosis of peptides and proteins through the mammalian blood-brain fluid barriers. In: Pardridge WM, editor. The blood-brain barrier: cellular and molecular biology. New York: Raven Press, 1993: 165–99
8.
Davson H, Segal MB. Physiology of the CSF and blood-brain barriers. Boca Raton (FL): CRC Press, 1996
9.
Pardridge WM. Peptide drug delivery to the brain. New York: Raven Press, 1991
10.
Kastin AJ, Pan W, Maness LM, et al. Peptides crossing the blood-brain barrier: some unusual observations. Brain Res 1999; 848: 96–100PubMedCrossRef
11.
12.
Pardridge WM. CNS drug design based on principles of blood-brain barrier transport. J Neurochem 1998; 70: 1781–92PubMedCrossRef
13.
Langer R. Drug delivery and targeting. Nature 1998; 392 Suppl.: S5–10
14.
Putney SD, Burke PA. Improving protein therapeutics with sustained-release formulations. Nat Biotechnol 1998; 16(2): 153–7PubMedCrossRef
15.
Prentis RA, Lis Y, Walker SR. Pharmaceutical innovation by the seven UK-owned pharmaceutical companies (1964–1985). Br J Clin Pharmacol 1988; 25: 387–96PubMedCrossRef
16.
Verrall M. Lay-offs follow suspension of clinical trials of protein. Nature 1994; 370: 6PubMed
17.
Loughlin SE. Neurotrophic factors. San Diego (CA): Academic Press Inc., 1993
18.
Apfel SC, Water TRVD, Koszer S. Clinical applications of neurotrophic factors. Philadelphia (PA): Lippincott-Raven Publishers, 1997
19.
Bregman BS, Broude E, McAtee M, et al. Transplants and neurotrophic factors prevent atrophy of mature CNS neurons after spinal cord injury. Exp Neurol 1998; 149(1): 13–27PubMedCrossRef
20.
Bregman BS, McAtee M, Dai HN, et al. Neurotrophic factors increase axonal growth after spinal cord injury and transplantation in the adult rat. Exp Neurol 1997; 148(2): 475–94PubMedCrossRef
21.
Grill R, Murai K, Blesch A, et al. Cellular delivery of neurotrophin-3 promotes corticospinal axonal growth and partial functional recovery after spinal cord injury. J Neurosci 1997; 17(14): 5560–72PubMed
22.
Ye JH, Houle JD. Treatment of the chronically injured spinal cord with neurotrophic factors can promote axonal regeneration from supraspinal neurons. Exp Neurol 1997; 143(1): 70–81PubMedCrossRef
23.
24.
Walsh G. Nervous excitement over neurotrophic factors. Biol Technol 1995; 13: 1167–71
25.
Johnson JE. Neurotrophic factors. In: Zigmond MJ, Bloom FE, Landis SC, et al., editors. Fundamental neuroscience. San Diego (CA): Academic Press, 1999: 611–35
26.
Glass DJ, Yancopoulos GD. The neurotrophins and their receptors. Trends Cell Biol 1993; 3: 262–7PubMedCrossRef
27.
Cordon-Cardo C, Tapley P, Jing SQ, et al. The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3. Cell 1991; 66(1): 173–83PubMedCrossRef
28.
Soppet D, Escandon E, Maragos J, et al. The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Cell 1991; 65(5): 895–903PubMedCrossRef
29.
Swen JS, Flanagan TR, Wiggans TG. Assessing commercial potential of central nervous system delivery approaches. In: Flanagan TR, Emerich DF, Winn SR, editors. Methods in neurosciences. San Diego (CA): Academic Press, 1994: 485–98
30.
Mufson EJ, Kroin JS, Sendera TJ, et al. Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative disease. Prog Neurobiol 1999; 57: 451–84PubMedCrossRef
31.
Teng YD, Mocchetti I, Taveira-DaSilva AM, et al. Basic fibroblast growth factor increases long-term survival of spinal motor neurons and improves respiratory function after experimental spinal cord injury. J Neurosci 1999; 19(16): 7037–47PubMed
32.
Cheng H, Cao Y, Olson L. Spinal cord repair in adult paraplegic rats: partial restoration of hind limb function. Science 1996; 273(5274): 510–3PubMedCrossRef
33.
Fisher M, Meadows M-E, Do T, et al. Delayed treatment with intravenous basic fibroblast growth factor reduces infarct size following permanent focal cerebral ischemia in rats. J Cereb Blood Flow Metab 1995; 15: 953–9PubMedCrossRef
34.
Cuevas P, Carceller F, Munoz-Willery I, et al. Intravenous fibroblast growth factor penetrates the blood-brain barrier and protects hippocampal neurons against ischemia-reperfusion injury. Surg Neurol 1998; 49(1): 77–83PubMedCrossRef
35.
Teng YD, Mocchetti I, Wrathall JR. Basic and acidic fibroblast growth factors protect spinal motor neurones in vivo after experimental spinal cord injury. Eur J Neurosci 1998; 10(2): 798–802PubMedCrossRef
36.
Guo Q, Sebastian L, Sopher BL, et al. Neurotrophic factors [activity-dependent neurotrophic factor (ADNF) and basic fibroblast growth factor (bFGF)] interrupt excitotoxic neurodegenerative cascades promoted by a PS1 mutation. Proc Natl Acad Sci U S A 1999; 96(7): 4125–30PubMedCrossRef
37.
Eckenstein FP. Fibroblast growth factors in the nervous system. J Neurobiol 1994; 25(11): 1467–80PubMedCrossRef
38.
39.
Murphy M, Dutton R, Koblar S, et al. Cytokines which signal through the LIF receptor and their actions in the nervous system. Prog Neurobiol 1997; 52(5): 355–78PubMedCrossRef
40.
Yamakuni H, Minami M, Satoh M. Localization of mRNA for leukemia inhibitory factor receptor in the adult rat brain. J Neuroimmunol 1996; 70(1): 45–53PubMedCrossRef
41.
Pennica D, Shaw KJ, Swanson TA, et al. Cardiotrophin-1. Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex. J Biol Chem 1995; 270(18): 10915–22PubMedCrossRef
42.
Pennica D, Wood WI, Chien KR. Cardiotrophin-1: a multifunctional cytokine that signals via LIF receptor-gp 130 dependent pathways. Cytokine Growth Factor Rev 1996; 7(1): 81–91PubMedCrossRef
43.
Robledo O, Fourcin M, Chevalier S, et al. Signaling of the cardiotrophin-1 receptor. Evidence for a third receptor component. J Biol Chem 1997; 272(8): 4855–63PubMedCrossRef
44.
Kurek JB, Radford AJ, Crump DE, et al. LIF (AM424), a promising growth factor for the treatment of ALS. J Neurol Sci 1998; 160 Suppl. 1: S106–13PubMedCrossRef
45.
Blesch A, Uy HS, Grill RJ, et al. Leukemia inhibitory factor augments neurotrophin expression and corticospinal axon growth after adult CNS injury. J Neurosci 1999; 19(9): 3556–66PubMed
46.
Ebendal T, Bengtsson H, Soderstrom S. Bone morphogenetic proteins and their receptors: potential functions in the brain. J Neurosci Res 1998; 51(2): 139–46PubMedCrossRef
47.
Helm GA, Alden TD, Sheehan JP, et al. Bone morphogenetic proteins and bone morphogenetic protein gene therapy in neurological surgery: a review. Neurosurgery 2000; 46(5): 1213–22PubMedCrossRef
48.
Nishitoh H, Ichijo H, Kimura M, et al. Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5. J Biol Chem 1996; 271(35): 21345–52PubMedCrossRef
49.
Krieglstein K, Suter-Crazzolara C, Hotten G, et al. Trophic and protective effects of growth/differentiation factor 5, a member of the transforming growth factor-beta superfamily, on midbrain dopaminergic neurons. J Neurosci Res 1995; 42(5): 724–32PubMedCrossRef
50.
Sullivan AM, Opacka-Juffry J, Pohl J, et al. Neuroprotective effects of growth/differentiation factor 5 depend on the site of administration. Brain Res 1999; 818(1): 176–9PubMedCrossRef
51.
Strelau J, Sullivan A, Bottner M, et al. Growth/differentiation factor-15/macrophage inhibitory cytokine-1 is a novel trophic factor for midbrain dopaminergic neurons in vivo. J Neurosci 2000; 20(23): 8597–603PubMed
52.
Wang Y, Lin SZ, Chiou AL, et al. Glial cell line-derived neurotrophic factor protects against ischemia-induced injury in the cerebral cortex. J Neurosci 1997; 17(11): 4341–8PubMed
53.
Watabe K, Ohashi T, Sakamoto T, et al. Rescue of lesioned adult rat spinal motoneurons by adenoviral gene transfer of glial cell line-derived neurotrophic factor. J Neurosci Res 2000; 60(4): 511–9PubMedCrossRef
54.
Perez-Navarro E, Akerud P, Marco S, et al. Neurturin protects striatal projection neurons but not interneurons in a rat model of Huntington’s disease. Neuroscience 2000; 98(1): 89–96PubMedCrossRef
55.
Milbrandt J, de Sauvage FJ, Fahrner TJ, et al. Persephin, a novel neurotrophic factor related to GDNF and neurturin. Neuron 1998; 20(2): 245–53PubMedCrossRef
56.
Masure S, Cik M, Hoefnagel E, et al. Mammalian a-4, a divergent member of the GFRa family of coreceptors for glial cell line-derived neurotrophic factor family ligands, is a receptor for the neurotrophic factor persephin. J Biol Chem 2000; 275(50): 39427–34PubMedCrossRef
57.
Kotzbauer PT, Lampe PA, Heuckeroth RO, et al. Neurturin, a relative of glial-cell-line-derived neurotrophic factor. Nature 1996; 384(6608): 467–70PubMedCrossRef
58.
Golden JP, Baloh RH, Kotzbauer PT, et al. Expression of neurturin, GDNF, and their receptors in the adult mouse CNS. J Comp Neurol 1998; 398(1): 139–50PubMedCrossRef
59.
GFR(alpha) Nomenclature Committee. Nomenclature of GPI-linked receptors for the GDNF ligand family. GFR(alpha) Nomenclature Committee. Neuron 1997; 19(3): 485
60.
Bilak MM, Shifrin DA, Corse AM, et al. Neuroprotective utility and neurotrophic action of neurturin in postnatal motor neurons: comparison with GDNF and persephin. Mol Cell Neurosci 1999; 13(5): 326–36PubMedCrossRef
61.
Baloh RH, Tansey MG, Lampe PA, et al. Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex. Neuron 1998; 21(6): 1291–302PubMedCrossRef
62.
Henrich-Noack P, Prehn JH, Krieglstein J. TGF-beta 1 protects hippocampal neurons against degeneration caused by transient global ischemia. Dose-response relationship and potential neuroprotective mechanisms. Stroke 1996; 27(9): 1609–14; discussion 15PubMedCrossRef
63.
Pratt BM, McPherson JM. TGF-beta in the central nervous system: potential roles in ischemic injury and neurodegenerative diseases. Cytokine Growth Factor Rev 1997; 8(4): 267–92PubMedCrossRef
64.
65.
Gozes I, Davidson A, Gozes Y, et al. Antiserum to activity-dependent neurotrophic factor produces neuronal cell death in CNS cultures: immunological and biological specificity. Brain Res Dev Brain Res 1997; 99(2): 167–75PubMedCrossRef
66.
Brenneman DE, Gozes I. A femtomolar-acting neuroprotective peptide. J Clin Invest 1996; 97(10): 2299–307PubMedCrossRef
67.
Heldin CH, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 1999; 79(4): 1283–316PubMed
68.
Gotz R, Koster R, Winkler C, et al. Neurotrophin-6 is a new member of the nerve growth factor family. Nature 1994; 372(6503): 266–9PubMedCrossRef
69.
Nilsson AS, Fainzilber M, Falck P, et al. Neurotrophin-7: a novel member of the neurotrophin family from the zebrafish. FEBS Lett 1998; 424(3): 285–90PubMedCrossRef
70.
Martin-Zanca D, Hughes SH, Barbacid M. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature 1986; 319(6056): 743–8PubMedCrossRef
71.
72.
Squinto SP, Stitt TN, Aldrich TH, et al. trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor. Cell 1991; 65(5): 885–93PubMedCrossRef
73.
Knusel B, Michel PP, Schwaber JS, et al. Selective and nonselective stimulation of central cholinergic and dopaminergic development in vitro by nerve growth factor, basic fibroblast growth factor, epidermal growth factor, insulin and the insulin-like growth factors I and II. J Neurosci 1990; 10(2): 558–70PubMed
74.
Knusel B, Winslow JW, Rosenthal A, et al. Promotion of central cholinergic and dopaminergic neuron differentiation by brain-derived neurotrophic factor but not neurotrophin 3. Proc Natl Acad Sci U S A 1991; 88(3): 961–5PubMedCrossRef
75.
Nishimura T, Nakatake Y, Konishi M, et al. Identification of a novel FGF, FGF-21, preferentially expressed in liver. Biochim Biophys Acta 2000; 1492: 203–6PubMedCrossRef
76.
Masiakowski P, Liu H, Radziejewski C, et al. Recombinant human and rat ciliary neurotrophic factors. J Neurochem 1991; 57: 1003–12PubMedCrossRef
77.
Reddi AH. Role of morphogenetic proteins in skeletal tissue engineering and regeneration. Nat Biotechnol 1998; 16(3): 247–52PubMedCrossRef
78.
Massague J. TGFb signaling: receptors, transducers, and mad proteins. Cell 1996; 85: 947–50PubMedCrossRef
79.
Morrison R. Epidermal growth factor: structure, expression, and functions in the central nervous system. In: Loughlin SE, Fallon JH, editors. Neurotrophic factors. San Diego (CA): Academic Press, Inc., 1993: 339–57
80.
Minghetti L, Goodearl AD, Mistry K, et al. Glial growth factors I–III are specific mitogens for glial cells. J Neurosci Res 1996; 43(6): 684–93PubMedCrossRef
81.
Mahanthappa NK, Anton ES, Matthew WD. Glial growth factor 2, a soluble neuregulin, directly increases Schwann cell motility and indirectly promotes neurite outgrowth. J Neurosci 1996; 16(15): 4673–83PubMed
82.
LeRoith D, Werner H, Faria TN, et al. CTR. Insulin-like growth factor receptors: implications for nervous system function. Ann N Y Acad Sci 1993; 692: 22–32PubMedCrossRef
83.
Adamo M, Raizada MK, LeRoith D. Insulin and insulin-like growth factor receptors in the nervous system. Mol Neurobiol 1989; 3: 71–100PubMedCrossRef
84.
Baxter RC, Binoux MA, Clemmons DR, et al. Recommendations for nomenclature of the insulin-like growth factor binding protein superfamily. J Clin Endocrinol Metab 1998; 83(9): 3213PubMedCrossRef
85.
Raines EW, Ross R. Platelet-derived growth factor. I. High yield purification and evidence for multiple forms. J Biol Chem 1982; 257(9): 5154–60PubMed
86.
Fretto LJ, Snape AJ, Tomlinson JE, et al. Mechanism of platelet-derived growth factor (PDGF) AA, AB, and BB binding to alpha and beta PDGF receptor. J Biol Chem 1993; 268(5): 3625–31PubMed
87.
Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science 2001; 291: 1304–51PubMedCrossRef
88.
International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 2001; 409: 860–921CrossRef
89.
90.
Desai MM, Zhang P, Hennessy CH. Surveillance for morbidity and mortality among older adults. United States, 1995–1996. Mor Mortal Wkly Rep CDC Surveill Summ 1999; 48(8): 7–25
91.
Shoulson I. Experimental therapeutics of neurodegenerative disorders: unmet needs. Science 1998; 282: 1072–4PubMedCrossRef
92.
Hock C, Heese K, Hulette C, et al. Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch Neurol 2000; 57(6): 846–51PubMedCrossRef
93.
Hock C, Heese K, Muller-Spahn F, et al. Increased CSF levels of nerve growth factor in patients with Alzheimer’s disease. Neurology 2000; 54(10): 2009–11PubMedCrossRef
94.
Vawter MP, Dillon-Carter O, Tourtellotte WW, et al. TGFbeta2 concentrations are elevated in Parkinson’s disease in ventricular cerebrospinal fluid. Exp Neurol 1996; 142(2): 313–22PubMedCrossRef
95.
Capsoni S, Ugolini G, Comparini A, et al. Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice. Proc Natl Acad Sci U S A 2000; 97(12): 6826–31PubMedCrossRef
96.
Arakawa Y, Sendtner M, Thoenen H. Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines. J Neurosci 1990; 10(11): 3507–15PubMed
97.
Hefti F. Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections. J Neurosci 1986; 6(8): 2155–62PubMed
98.
Sendtner M, Holtmann B, Kolbeck R, et al. Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section. Nature 1992; 360(6406): 757–9PubMedCrossRef
99.
Gluckman P, Klempt N, Guan J, et al. A role for IGF-I in the rescue of CNS neurons following hypoxic ischemic injury. Biochem Biophys Res Commun 1992; 182(2): 593–9PubMedCrossRef
100.
Gross CC. Neurogenesis in the adult brain: death of a dogma. Nat Rev Neurosci 2000; 1: 67–73PubMedCrossRef
101.
Eriksson PS, Perfilieva E, Bjork-Eriksson T, et al. Neurogenesis in the adult human hippocampus. Nat Med 1998; 4(11): 1313–7PubMedCrossRef
102.
Wagner JP, Black IB, DiCicco-Bloom E. Stimulation of neonatal and adult brain neurogenesis by subcutaneous injection of basic fibroblast growth factor. J Neurosci 1999; 19(14): 6006–16PubMed
103.
Aberg MA, Aberg ND, Hedbacker H, et al. Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci 2000; 20(8): 2896–903PubMed
104.
Emilien G, Beyreuther K, Masters CL, et al. Prospects for pharmacological intervention in Alzheimer disease. Arch Neurol 2000; 57: 454–9PubMedCrossRef
105.
Giacobini E. Cholinesterase inhibitor therapy stabilizes symptoms of Alzheimer disease. Alzheimer Dis Assoc Disord 2000; 14 Suppl. 1: S3–10PubMedCrossRef
106.
107.
Koliatsos VE, Clatterbuck RE, Nauta HJ, et al. Human nerve growth factor prevents degeneration of basal forebrain cholinergic neurons in primates. Ann Neurol 1991; 30(6): 831–40PubMedCrossRef
108.
Davson H, Welch K, Segal MB. Physiology and pathophysiology of the cerebrospinal fluid. Edinburgh: Churchill Livingstone, 1987
109.
Greitz D. Cerebrospinal fluid circulation and associated intracranial dynamics: a radiologic investigation using MR imaging and radionuclide cisternography. Acta Radiol 1993; 34 Suppl. 386: 1–23
110.
Foldi M. The brain and the lymphatic system (I). Lymphology 1996; 29: 1–9PubMed
111.
Kida S, Pantazis A, Weiler RO. CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathol Appl Neurobiol 1993; 19: 480–8PubMedCrossRef
112.
Lowhagen P, Johansson BB, Nordborg C. The nasal route of cerebrospinal fluid drainage in man. A light-microscope study. Neuropathol Appl Neurobiol 1994; 20: 543–50PubMedCrossRef
113.
Frey WH, Liu J, Chen X, et al. Delivery of 125I-NGF to the brain via the olfactory route. Drug Deliv 1997; 4: 87–92CrossRef
114.
Thorne RG, Emory CR, Ala TA, et al. Quantitative analysis of the olfactory pathway for drug delivery to the brain. Brain Res 1995; 692: 278–82PubMedCrossRef
115.
Kroin JS. Intrathecal drug administration. Present use and future trends. Clin Pharmacokinet 1992; 22(5): 319–26PubMedCrossRef
116.
117.
McMartin C. Peptide and protein drugs. In: Welling PG, Balant LP, editors. Handbook of experimental pharmacology. Berlin: Springer-Verlag, 1994: 371–82
118.
Egleton RD, Davis TP. Bioavailability and transport of peptides and peptide drugs into the brain. Peptides 1997; 18(9): 1431–9PubMedCrossRef
119.
Braeckman R. Pharmacokinetics and pharmacodynamics of protein therapeutics. In: Reid RE, editor. Peptide and protein drug analysis. New York: Marcel Dekker, Inc., 2000: 633–69
120.
121.
Taipale J, Keski-Oja J. Growth factors in the extracellular matrix. FASEB J 1997; 11(1): 51–9PubMed
122.
Øie S, Benet LZ. The effect of route of administration and distribution on drug action. In: Banker GS, Rhodes CT, editors. Modern pharmaceutics. 3rd ed. New York: Marcel Dekker, Inc., 1996: 155–78
123.
Hunt CA, MacGregor RD, Siegel RA. Engineering targeted in vivo drug delivery: I. The physiological and physicochemical principles governing opportunities and limitations. Pharm Res 1986; 3: 333–44CrossRef
124.
Rowland M, McLachlan A. Pharmacokinetic considerations of regional administration and drug targeting: influence of site of input in target tissue and flux of binding protein. J Pharmacokinet Biopharm 1996; 24(4): 369–87PubMed
125.
McDonald NQ, Chao MV. Structural determinants of neurotrophin action. J Biol Chem 1995; 270(34): 19669–72PubMedCrossRef
126.
127.
Perdue JF. Chemistry, structure, and function of insulin-like growth factors and their receptors: a review. Can J Biochem Cell Biol 1984; 62: 1237–45PubMedCrossRef
128.
Thomas KA. Biochemistry and molecular biology of fibroblast growth factors. In: Loughlin SE, Fallon JH, editors. Neurotrophic factors. San Diego (CA): Academic Press, Inc., 1993: 285–312
129.
Savage CR, Inagami T, Cohen S. The primary structure of epidermal growth factor. J Biol Chem 1972; 247: 7612–21PubMed
130.
Pan W, Banks WA, Kastin AJ. Permeability of the blood-brain barrier to neurotrophins. Brain Res 1998; 788: 87–94PubMedCrossRef
131.
Barnett J, Chow J, Nguyen B, et al. Physicochemical characterization of recombinant human nerve growth factor produced in insect cells with a baculovirus vector. J Neurochem 1991; 57: 1052–61PubMedCrossRef
132.
Goldstein LD, Reynolds CP, Perez-Polo JR. Isolation of human nerve growth factor from placental tissue. Neurochem Res 1978; 3: 175–83PubMedCrossRef
133.
Rusenko KW, Stach RW Interaction of [125I]β nerve growth factor with acidic proteins. Neurochem Res 1981; 6(3): 287–300PubMedCrossRef
134.
Murase K, Takeuchi R, Iwata E, et al. Developmental changes in nerve growth factor level in rat serum. J Neurosci Res 1992; 33(2): 282–8PubMedCrossRef
135.
Liebl DJ, Koo PH. Comparative binding of neurotrophins (NT-3, CNTF and NGF) and various cytokines to alpha 2-macroglobulin. Biochem Biophys Res Commun 1993; 193(3): 1255–61PubMedCrossRef
136.
Nguyen CB, Szonyi E, Sadick MD, et al. Stability and interactions of recombinant human nerve growth factor in different biological matrices: in vitro and in vivo studies. Drug Metab Dispos 2000; 28(5): 590–7PubMed
137.
DiStefano PS, Johnson EMJ. Identification of a truncated form of the nerve growth factor receptor. Proc Natl Acad Sci U S A 1988; 85(1): 270–4PubMedCrossRef
138.
Rinderknecht E, Humbel RE. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem 1978; 253(8): 2769–76PubMed
139.
Li CH, Yamashiro D, Gospodarowicz D, et al. Total synthesis of insulin-like growth factor I (somatomedin C). Proc Natl Acad Sci U S A 1983; 80: 2216–20PubMedCrossRef
140.
Frystyk J, Skjaerbaek C, Dinesen B, et al. Free insulin-like growth factors (IGF-I and IGF-II) in human serum. FEBS Lett 1994; 348: 185–91PubMedCrossRef
141.
Spagnoli A, Rosenfeld RG. Insulinlike growth factor binding proteins. Curr Opin Endocrinol Diabetes 1997; 4: 1–9CrossRef
142.
Scott CD, Ballesteros M, Madrid J, et al. Soluble insulin-like growth factor-II/mannose 6-P receptor inhibits deoxyribonucleic acid synthesis in cultured rat hepatocytes. Endocrinology 1996; 137(3): 873–8PubMedCrossRef
143.
Karey KP, Sirbasku DA. Glutaraldehyde fixation increases retention of low molecular weight proteins (growth factors) transferred to nylon membranes for western blot analysis. Anal Biochem 1989; 178: 255–9PubMedCrossRef
144.
Deguchi Y, Naito T, Yuge T, et al. Blood-brain barrier transport of 125I-labeled basic fibroblast growth factor. Pharm Res 2000; 17(1): 63–9PubMedCrossRef
145.
Dennis PA, Saksela O, Harpel P, et al. Alpha 2-macroglobulin is a binding protein for basic fibroblast growth factor. J Biol Chem 1989; 264(13): 7210–6PubMed
146.
Hanneken A, Ying W, Ling N, et al. Identification of soluble forms of the fibroblast growth factor receptor in blood. Proc Natl Acad Sci U S A 1994; 91(19): 9170–4PubMedCrossRef
147.
Antoniades HN, Scher CD, Stiles CD. Purification of human platelet-derived growth factor. Proc Natl Acad Sci U S A 1979; 76(4): 1809–13PubMedCrossRef
148.
Deuel TF, Huang JS, Proffitt RT, et al. Human platelet-derived growth factor. Purification and resolution into two active protein fractions. J Biol Chem 1981; 256(17): 8896–9PubMed
149.
Gonias SL, Carmichael A, Mettenburg JM, et al. Identical or overlapping sequences in the primary structure of human alpha(2)-macroglobulin are responsible for the binding of nerve growth factor-beta, platelet-derived growth factor-BB, and transforming growth factor-beta. J Biol Chem 2000; 275(8): 5826–31PubMedCrossRef
150.
Nexo E, Jorgensen PE, Hansen MR. Human epidermal growth factor-on molecular forms present in urine and blood. Regul Pept 1992; 42: 75–84PubMedCrossRef
151.
152.
Kim DC, Sugiyama Y, Fuwa T, et al. Kinetic analysis of the elimination process of human epidermal growth factor (hEGF) in rats. Biochem Pharmacol 1989; 38(2): 241–9PubMedCrossRef
153.
Nieto-Sampedro M, Broderick JT. A soluble brain molecule related to epidermal growth factor receptor is a mitogen inhibitor for astrocytes. J Neurosci Res 1989; 22(1): 28–35PubMedCrossRef
154.
Negro A, Corona G, Bigon E, et al. Synthesis, purification, and characterization of human ciliary neuronotrophic factor from E. coli. J Neurosci Res 1991; 29: 251–60PubMedCrossRef
155.
Marquardt H, Hunkapiller MW, Hood LE, et al. Rat transforming growth factor type 1: structure and relation to epidermal growth factor. Science 1984; 223: 1079–82PubMedCrossRef
156.
Kuo K-W, Yeh H-W, Chu DZJ, et al. Separation and microanalysis of growth factors by Phast system gel electrophoresis and by DNA synthesis in cell culture. J Chromatogr B Biomed Sci Appl 1991; 543: 463–70
157.
Pan W, Vallance K, Kastin AJ. TGFa and the blood-brain barrier: accumulation in cerebral vasculature. Exp Neurol 1999; 160: 454–9PubMedCrossRef
158.
Malamud D, Drysdale JW. Isoelectric points of proteins: a table. Anal Biochem 1978; 86: 620–47PubMedCrossRef
159.
Shulz RM, Liebman MN. Proteins I: composition and structure. In: Devlin TM, editor. Textbook of biochemistry with clinical correlations. 3rd ed. New York: Wiley, 1992: 25–88
160.
Banks WA, Kastin AJ. Peptides and the blood-brain barrier: lipophilicity as a predictor of permeability. Brain Res Bull 1985; 15: 287–92PubMedCrossRef
161.
Rockich KT, Hatten JC, Kryscio RJ, et al. Effect of recombinant human growth hormone and insulin-like growth factor-1 administration on IGF-1 and IGF-binding protein-3 levels in brain injury. Pharmacotherapy 1999; 19(12): 1432–6PubMedCrossRef
162.
Kupfer SR, Underwood LE, Baxter RC, et al. Enhancement of the anabolic effects of growth hormone and insulin-like growth factor I by use of both agents simultaneously. J Clin Invest 1993; 91(2): 391–6PubMedCrossRef
163.
Blomback B, Hanson LA, editors. Plasma proteins. Chichester: John Wiley & Sons, 1979
164.
Calissano P, Cozzari C. Interaction of nerve growth factor with the mouse-brain neurotubule protein(s). Proc Natl Acad Sci U S A 1974; 71(5): 2131–5PubMedCrossRef
165.
Hoener MC, Varon S. Reversible sedimentation and masking of nerve growth factor (NGF) antigen by high molecular weight fractions from rat brain. Brain Res 1997; 772: 1–8PubMedCrossRef
166.
Koo PH, Stach RW Interaction of nerve growth factor with murine alpha-macroglobulin. J Neurosci Res 1989; 22(3): 247–61PubMedCrossRef
167.
Hintzen RQ, van Lier RA, Kuijpers KC, et al. Elevated levels of a soluble form of the T cell activation antigen CD27 in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 1991; 35(1-3): 211–7PubMedCrossRef
168.
Clemmons DR, Jones JI, Busby WH, et al. Role of insulin-like growth factor binding proteins in modifying IGF actions. Ann N Y Acad Sci 1993; 692: 10–21PubMedCrossRef
169.
Tanaka Y, Kitao K, Hata T, et al. Kidney as an important metabolic organ for recombinant human insulin-like growth factor-I. Res Commun Mol Pathol Pharmacol 1997; 96(3): 267–76PubMed
170.
Froesch ER, Zapf J. Insulin-like growth factors and insulin: comparative aspects. Diabetologia 1985; 28: 485–93PubMedCrossRef
171.
Frystyk J, Gronbaek H, Skjaerbaek C, et al. Effect of hyperthyroidism on circulating levels of free and total IGF-1 and IGFBPs in rats. Am J Physiol 1995; 269: E840–5PubMed
172.
Skjaerbaek C, Frystyk J, Grofte T, et al. Serum free insulin-like growth factor-I is dose-dependently decreased by methylprednisolone and related to body weight changes in rats. Growth Horm IGF Res 1999; 9: 74–80PubMedCrossRef
173.
Loddick SA, Liu X-J, Lu Z-X, et al. Displacement of insulin-like growth factors from their binding proteins as a potential treatment for stroke. Proc Natl Acad Sci U S A 1998; 95: 1894–8PubMedCrossRef
174.
Ocrant I, Fay CT, Parmelee JT. Characterization of insulin-like growth factor binding proteins produced in the rat central nervous system. Endocrinology 1990; 127(3): 1260–7PubMedCrossRef
175.
LeRoith D, Roberts Jr CT, Werner H, Bondy C, et al. Insulin-like growth factors in the brain. In: Loughlin SE, Fallon JH, editors. Neurotrophic factors. San Diego (CA): Academic Press, Inc., 1993: 391–414
176.
Clairmont KB, Czech MP. Extracellular release as the major degradative pathway of the insulin-like growth factor II/mannose 6-phosphate receptor. J Biol Chem 1991; 266(19): 12131–4PubMed
177.
Hanneken A, Frautschy S, Galasko D, et al. A fibroblast growth factor binding protein in human cerebral spinal fluid. Neuroreport 1995; 6(6): 886–8PubMedCrossRef
178.
Zaina S, Newton RV, Paul MR, et al. Local reduction of organ size in transgenic mice expressing a soluble insulin-like growth factor II/mannose-6-phosphate receptor. Endocrinology 1998; 139(9): 3886–95PubMedCrossRef
179.
Fung LK, Ewend MG, Sills A, et al. Pharmacokinetics of interstitial delivery of carmustine, 4-hydroperoxycyclophosphamide, and paclitaxel from a biodegradable polymer implant in the monkey brain. Cancer Res 1998; 58(4): 672–84PubMed
180.
Zoli M, Jansson A, Syková E, et al. Volume transmission in the CNS and its relevance for neuropsychopharmacology. Trends Pharmacol Sci 1999; 20: 142–50PubMedCrossRef
181.
Rennels ML, Gregory TF, Blaumanis OR, et al. Evidence for a ‘paravascular’ fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space. Brain Res 1985; 326(1): 47–63PubMedCrossRef
182.
Nicholson C, Syková E. Extracellular space structure revealed by diffusion analysis. Trends Neurosci 1998; 21(5): 207–15PubMedCrossRef
183.
Krewson CE, Klarman ML, Saltzman WM. Distribution of nerve growth factor following direct delivery to brain interstitium. Brain Res 1995; 680(1-2): 196–206PubMedCrossRef
184.
Muramatsu N, Minton AP. Tracer diffusion of globular proteins in concentrated protein solutions. Proc Natl Acad Sci U S A 1988; 85: 2984–8PubMedCrossRef
185.
186.
Fenstermacher J, Kaye T. Drug ‘diffusion’ within the brain. Ann N Y Acad Sci 1988; 531: 29–39PubMedCrossRef
187.
Tao L, Nicholson C. Diffusion of albumins in rat cortical slices and relevance to volume transmission. Neuroscience 1996; 75(3): 839–47PubMedCrossRef
188.
Nicholson C, Tao L. Hindered diffusion of high molecular weight compounds in brain extracellular microenvironment measured with integrative optical imaging. Biophys J 1993; 65(6): 2277–90PubMedCrossRef
189.
Busch NA, Kim T, Bloomfield VA. Tracer diffusion of proteins in DNA solutions. 2. Green fluorescent protein in crowded DNA solutions. Macromolecules 2000; 33: 5932–7CrossRef
190.
Berg HC. Random walks in biology. Princeton (NJ): Princeton University Press, 1993
191.
Saltzman WM, Mak MW, Mahoney MJ, et al. Intracranial delivery of recombinant nerve growth factor: release kinetics and protein distribution for three delivery systems. Pharm Res 1999; 16(2): 232–40PubMedCrossRef
192.
Haller MF, Saltzman WM. Localized delivery of proteins in the brain: can transport be customized? Pharm Res 1998; 15(3): 377–85PubMedCrossRef
193.
Ferguson IA, Schweitzer JB, Bartlett PF, et al. Receptor-mediated retrograde transport in CNS neurons after intraventricular administration of NGF and growth factors. J Comp Neurol 1991; 313(4): 680–92PubMedCrossRef
194.
Yan Q, Matheson C, Sun J, et al. Distribution of intracerebral ventricularly administered neurotrophins in rat brain and its correlation with Trk receptor expression. Exp Neurol 1994; 127: 23–36PubMedCrossRef
195.
Mufson EJ, Kroin JS, Liu Y-T, et al. Intrastriatal and intraventricular infusion of brain-derived neurotrophic factor in the cynomologous monkey: distribution, retrograde transport and co-localization with substantia nigra dopamine-containing neurons. Neuroscience 1996; 71(1): 179–91PubMedCrossRef
196.
Brightman MW. The intracerebral movement of proteins injected into blood and cerebrospinal fluid of mice. Prog Brain Res 1968; 29: 19–40PubMedCrossRef
197.
Hutchings M, Weller RO. Anatomical relationships of the pia mater to cerebral blood vessels in man. J Neurosurg 1986; 65(3): 316–25PubMedCrossRef
198.
Ichimura T, Fraser PA, Cserr HE Distribution of extracellular tracers in perivascular spaces of the rat brain. Brain Res 1991; 545(1-2): 103–13PubMedCrossRef
199.
Guan J, Beilharz EJ, Skinner SJ, et al. Intracerebral transportation and cellular localisation of insulin-like growth factor-1 following central administration to rats with hypoxic-ischemic brain injury. Brain Res 2000; 853(2): 163–73PubMedCrossRef
200.
Guan J, Skinner SJ, Beilharz EJ, et al. The movement of IGF-I into the brain parenchyma after hypoxic-ischaemic injury. Neuroreport 1996; 7(2): 632–6PubMedCrossRef
201.
Olson L, Backlund EO, Ebendal T, et al. Intraputaminal infusion of nerve growth factor to support adrenal medullary autografts in Parkinson’s disease. One-year follow-up of first clinical trial. Arch Neurol 1991; 48(4): 373–81PubMedCrossRef
202.
Olson L, Nordberg A, von Holst H, et al. Nerve growth factor affects 11C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient (case report). J Neural Transm Park Dis Dement Sect 1992; 4(1): 79–95PubMedCrossRef
203.
Jönhagen ME, Nordberg A, Amberla K, et al. Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 1998; 9: 246–57CrossRef
204.
Petty BG, Cornblath DR, Adornate BT, et al. The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann Neurol 1994; 36: 244–6PubMedCrossRef
205.
Cedarbaum JM, Chapman C, Charatan M, et al. The pharmacokinetics of subcutaneously administered recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis: relation to parameters of the acutephase response. The ALS CNTF Treatment Study (ACTS) Phase I–II Study Group. Clin Neuropharmacol 1995; 18(6): 500–14CrossRef
206.
Aebischer P, Schluep M, Deglon N, et al. Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nat Med 1996; 2(6): 696–9PubMedCrossRef
207.
Penn RD, Kroin JS, York MM, et al. Intrathecal ciliary neurotrophic factor delivery for treatment of amyotrophic lateral sclerosis (phase I trial). Neurosurgery 1997; 40(1): 94–9PubMed
208.
Ochs G, Giess R, Bendszus M, et al. Epi-arachnoidal drug deposit: a rare complication of intrathecal drug therapy. J Pain Symptom Manage 1999; 18(3): 229–32PubMedCrossRef
209.
Broadwell RD. Transcytosis of macromolecules through the blood-brain barrier: a cell biological perspective and critical appraisal. Acta Neuropathol (Berl) 1989; 79: 117–28CrossRef
210.
Broadwell RD, Balin BJ, Salcman M. Transcytotic pathway for blood-borne protein through the blood-brain barrier. Proc Natl Acad Sci U S A 1988; 85: 632–6PubMedCrossRef
211.
Poduslo JF, Curran GL, Berg CT. Macromolecular permeability across the blood-nerve and blood-brain barriers. Proc Natl Acad Sci U S A 1994; 91(12): 5705–9PubMedCrossRef
212.
Pan W, Banks WA, Fasold MB, et al. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 1998; 37(12): 1553–61PubMedCrossRef
213.
Friden PM, Walus LR, Watson P, et al. Blood-brain barrier penetration and in vivo activity of an NGF conjugate. Science 1993; 259: 373–7PubMedCrossRef
214.
Wu D, Pardridge WM. Neuroprotection with noninvasive neurotrophin delivery to the brain. Proc Natl Acad Sci U S A 1999; 96(1): 254–9PubMedCrossRef
215.
Jiao S, Miller PJ, Lapchak PA. Enhanced delivery of [125I]glial cell line-derived neurotrophic factor to the rat CNS following osmotic blood-brain barrier modification. Neurosci Lett 1996; 220(3): 187–90PubMedCrossRef
216.
Apfel SC. Neurotrophic factors in the therapy of diabetic neuropathy. Am J Med 1999; 107 Suppl. 2B: S34–42CrossRef
217.
Apfel SC, Kessler JA. Neurotrophic factors in the treatment of peripheral neuropathy. Ciba Found Symp 1996; 196: 98–108PubMed
218.
Hefti F, editor. Neurotrophic factors. Berlin: Springer-Verlag, 1999
219.
Cedarbaum JM, Chapman C, Charatan M, et al. A phase I study of recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis. The ALS CNTF Treatment Study (ACTS) Phase I–II Study Group. Clin Neuropharmacol 1995; 18(6): 515–32CrossRef
220.
Cedarbaum JM, Chapman C, Charatan M, et al. A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. ALS CNTF Treatment Study Group. Neurology 1996; 46(5): 1244–9CrossRef
221.
Boroujerdi MA, Sonksen PH, Jones RH. A compartmental model for simulation of IGF-I kinetics and metabolism. Methods Inf Med 1994; 33: 514–21PubMed
222.
Frystyk J, Hussain M, Skjaerbaek C, et al. The pharmacokinetics of free insulin-like growth factor-I in healthy subjects. Growth Horm IGF Res 1999; 9: 150–6PubMedCrossRef
223.
Skjaerbaek C, Frystyk J, Kaal A, et al. Circadian variation in serum free and total insulin-like growth factor (IGF)-I and IGF-II in untreated and treated acromegaly and growth hormone deficiency. Clin Endocrinol (Oxf) 2000; 52: 25–33CrossRef
224.
Reinhardt RR, Bondy CA. Insulin-like growth factors cross the blood-brain barrier. Endocrinology 1994; 135(5): 1753–61PubMedCrossRef
225.
Bondy CA, Lee W-H. Patterns of insulin-like growth factor and IGF receptor gene expression in the brain: functional implications. Ann N Y Acad Sci 1993; 692: 33–43PubMedCrossRef
226.
Pardridge WM. Transport of insulin-related peptides and glucose across the blood-brain barrier. Ann N Y Acad Sci 1993; 692: 126–37PubMedCrossRef
227.
Mackic JB, Weiss MH, Miao W, et al. Cerebrovascular accumulation and increased blood-brain barrier permeability to circulating Alzheimer’s amyloid beta peptide in aged squirrel monkey with cerebral amyloid angiopathy. J Neurochem 1998; 70(1): 210–5PubMedCrossRef
228.
Nitsch C, Goping G, Laursen H, et al. The blood-brain barrier to horseradish peroxidase at the onset of bicuculline-induced seizures in hypothalamus, pallidum, hippocampus, and other selected regions of the rabbit. Acta Neuropathol (Berl) 1986; 69(1-2): 1–16CrossRef
229.
Plateel M, Teissier E, Cecchelli R. Hypoxia dramatically increases the nonspecific transport of blood-borne proteins to the brain. J Neurochem 1997; 68(2): 874–7PubMedCrossRef
230.
Albayrak S, Zhao Q, Siesjo BK, et al. Effect of transient focal ischemia on blood-brain barrier permeability in the rat: correlation to cell injury. Acta Neuropathol (Berl) 1997; 94(2): 158–63CrossRef
231.
Preston E, Foster DO. Evidence for pore-like opening of the blood-brain barrierfollowing forebrain ischemia in rats. Brain Res 1997; 761(1): 4–10PubMedCrossRef
232.
Tuomanen E. Entry of pathogens into the central nervous system. FEMS Microbiol Rev 1996; 18(4): 289–99PubMedCrossRef
233.
de Vries HE, Blom-Roosemalen MC, de Boer AG, et al. Effect of endotoxin on permeability of bovine cerebral endothelial cell layers in vitro. J Pharmacol Exp Ther 1996; 277(3): 1418–23PubMed
234.
Moor AC, de Vries HE, de Boer AG, et al. The blood-brain barrier and multiple sclerosis. Biochem Pharmacol 1994; 47(10): 1717–24PubMedCrossRef
235.
Mahoney MJ, Saltzman WM. Millimeter-scale positioning of a nerve-growth-factor source and biological activity in the brain. Proc Natl Acad Sci U S A 1999; 96(8): 4536–9PubMedCrossRef
236.
Krewson CE, Saltzman WM. Transport and elimination of recombinant human NGF during long-term delivery to the brain. Brain Res 1996; 727(1-2): 169–81PubMedCrossRef
237.
Mahoney MJ, Saltzman WM. Controlled release of proteins to tissue transplants for the treatment of neurodegenerative disorders. J Pharm Sci 1996; 85(12): 1276–81PubMedCrossRef
238.
Krewson CE, Dause R, Mak M, et al. Stabilization of nerve growth factor in controlled release polymers and in tissue. J Biomater Sci Polym Ed 1996; 8(2): 103–17PubMedCrossRef
239.
Morse JK, Wiegand SJ, Anderson K, et al. Brain-derived neurotrophic factor (BDNF) prevents the degeneration of medial septal cholinergic neurons following fimbria transection. J Neurosci 1993; 13(10): 4146–56PubMed
240.
Venero JL, Hefti F, Knusel B. Trophic effect of exogenous nerve growth factor on rat striatal cholinergic neurons: comparison between intraparenchymal and intraventricular administration. Mol Pharmacol 1996; 49(2): 303–10PubMed
241.
Lapchak PA, Araujo DM, Carswell S, et al. Distribution of [125I]nerve growth factor in the rat brain following a single intraventricular injection: correlation with the topographical distribution of trkA messenger RNA-expressing cells. Neuroscience 1993; 54(2): 445–60PubMedCrossRef
242.
Emmett CJ, Stewart GR, Johnson RM, et al. Distribution of radioiodinated recombinant human nerve growth factor in primate brain following intracerebroventricular infusion. Exp Neurol 1996; 140: 151–60PubMedCrossRef
243.
Jonhagen ME. Nerve growth factor treatment in dementia. Alzheimer Dis Assoc Disord 2000; 14 Suppl. 1: S31–8PubMedCrossRef
244.
Kordower JH, Palfi S, Chen E-Y, et al. Clinicopathological findings following intraventricular glial-derived neurotrophic factor treatment in a patient with Parkinson’s disease. Ann Neurol 1999; 46(3): 419–24PubMedCrossRef
245.
Hao J, Ebendal T, Xu X, et al. Intracerebroventricular infusion of nerve growth factor induces pain-like response in rats. Neurosci Lett 2000; 286(3): 208–12PubMedCrossRef
246.
Johanson CE, Szmydynger-Chodobska J, Chodobski A, et al. Altered formation and bulk absorption of cerebrospinal fluid in FGF-2-induced hydrocephalus. Am J Physiol 1999; 277 (1 Pt 2): R263–71PubMed
247.
Dittrich F, Ochs G, Grobe-Wilde A, et al. Pharmacokinetics of intrathecally applied BDNF and effects on spinal motoneurons. Exp Neurol 1996; 141: 225–39PubMedCrossRef
248.
Gold BG. Axonal regeneration of sensory nerves is delayed by continuous intrathecal infusion of nerve growth factor. Neuroscience 1997; 76(4): 1153–8PubMedCrossRef
249.
Frey WH, Liu J, Thome RG, et al. Intranasal delivery of 125I-labeled nerve growth factor to the brain via the olfactory route. In: Iqbal K, Mortimer JA, Winblad B, et al., editors. Research advances in Alzheimer’s disease and related disorders. Chichester: John Wiley & Sons Ltd, 1995: 329–35
250.
Ilium L. Transport of drugs from the nasal cavity to the central nervous system. Eur J Pharm Sci 2000; 11: 1–18CrossRef
251.
Mathison S, Nagilla R, Kompella UB. Nasal route for direct delivery of solutes to the central nervous system: fact or fiction? J Drug Target 1998; 5: 415–41PubMedCrossRef
252.
Baker H, Spencer RF. Transneuronal transport of peroxidase-conjugated wheat germ agglutinin (WGA-HRP) from the olfactory epithelium to the brain of the adult rat. Exp Brain Res 1986; 63(3): 461–73PubMedCrossRef
253.
Broadwell RD, Balin BJ. Endocytic and exocytic pathways of the neuronal secretory process and trans-synaptic transfer of wheat germ agglutinin-horseradish peroxidase in vivo. J Comp Neurol 1985; 242: 632–50PubMedCrossRef
254.
Shipley MT. Transport of molecules from nose to brain: transneuronal anterograde and retrograde labeling in the rat olfactory system by wheat germ agglutinin-horseradish peroxidase applied to the nasal epithelium. Brain Res Bull 1985; 15(2): 129–42PubMedCrossRef
255.
Fawcett JR, Chen X, Rahman YE, et al. Previously reported nerve growth factor levels are underestimated due to an incomplete release from receptors and interaction with standard curve media. Brain Res 1999; 842(1): 206–10PubMedCrossRef
256.
Chen X-Q, Fawcett JR, Rahman Y-E, et al. Delivery of nerve growth factor to the brain via the olfactory pathway. J Alzheimer Dis 1998; 1: 35–44
257.
Gozes I, Bardea A, Reshef A, et al. Neuroprotective strategy for Alzheimer disease: intranasal administration of a fatty neuropeptide. Proc Natl Acad Sci U S A 1996; 93: 427–32PubMedCrossRef
258.
Gozes I, Giladi E, Pinhasov A, et al. Activity-dependent neurotrophic factor: intranasal administration of femtomolar-acting peptides improve performance in a water maze. J Pharmacol Exp Ther 2000; 293(3): 1091–8PubMed
259.
Kucheryanu VG, Kryzhanovsky GN, Kudrin VS, et al. Intranasal fibroblast growth factors: delivery into the brain exerts antiparkinsonian effect in mice. In: Torchilin V, Veronese FM, editors. Proceedings of the 26th International Symposium on Controlled Release of Bioactive Materials; 1999 Jun 20–23; Boston. Deerfield (IL): Controlled Release Society, Inc., 1999: 643–4
260.
Date I, Notter MF, Feiten SY, et al. MPTP-treated young mice but not aging mice show partial recovery of the nigrostriatal dopaminergic system by stereotaxic injection of acidic fibroblast growth factor (aFGF). Brain Res 1990; 526(1): 156–60PubMedCrossRef
261.
Date I, Yoshimoto Y, Imaoka T, et al. Enhanced recovery of the nigrostriatal dopaminergic system in MPTP-treated mice following intrastriatal injection of basic fibroblast growth factor in relation to aging. Brain Res 1993; 621(1): 150–4PubMedCrossRef
262.
Dahlin M, Bergman U, Jansson B, et al. Transfer of dopamine in the olfactory pathway following nasal administration in mice. Pharm Res 2000; 17(6): 737–42PubMedCrossRef
263.
Chen X. Investigation of delivery of nerve growth factor (NGF) to the central nervous system (CNS) via the olfactory neural pathway [PhD thesis]. Minneapolis (MN): University of Minnesota, 2000
264.
DeSesso JM. The relevance to humans of animal models for inhalation studies of cancer in the nose and upper airways. Qual Assur 1993; 2(3): 213–31PubMed
265.
Roberts E. Alzheimer’s disease may begin in the nose and may be caused by aluminosilicates. Neurobiol Aging 1986; 7: 561–7PubMedCrossRef
266.
Okuyama S. The first attempt at radioisotopic evaluation of the integrity of the nose-brain barrier. Life Sci 1997; 60(21): 1881–4PubMedCrossRef
267.
Riekkinen P, Legros J-J, Sennef C, et al. Penetration of DGAVP (Org 5667) across the blood-brain barrier in human subjects. Peptides 1987; 8: 261–5PubMedCrossRef
268.
Kern W, Born J, Schreiber H, et al. Central nervous system effects of intranasally administered insulin during euglycemia in men. Diabetes 1999; 48: 557–63PubMedCrossRef
269.
Kern W, Schiefer B, Schwarzenburg J, et al. Evidence for central nervous effects of corticotropin-releasing hormone on gastric acid secretion in humans. Clin Neuroendocrinol 1997; 65: 291–8CrossRef
270.
Perras B, Marshall L, Kohler G, et al. Sleep and endocrine changes after intranasal administration of growth hormone-releasing hormone in young and aged humans. Psychoneuro-endocrinology 1999; 24: 743–57CrossRef
271.
Pietrowsky R, Struben C, Molle M, et al. Brain potential changes after intranasal vs. intravenous administration of vasopressin: evidence for a direct nose-brain pathway for peptide effects in humans. Biol Psychiatry 1996; 39: 332–40PubMedCrossRef
272.
Pietrowsky R, Thiemann A, Kern W, et al. A nose-brain pathway for psychotropic peptides: evidence from a brain evoked potential study with cholecystokinin. Psychoneuroendocrinology 1996; 21(6): 559–72PubMedCrossRef
273.
Fehm-Wolfsdorf G, Born J. Behavioral effects of neurohypophyseal peptides in healthy volunteers: 10 years of research. Peptides 1991; 12: 1399–406PubMedCrossRef
274.
Sakane T, Akizuki M, Yamashita S, et al. Direct drug transport from the rat nasal cavity to the cerebrospinal fluid: the relation to the dissociation of the drug. J Pharm Pharmacol 1994; 46: 378–9PubMedCrossRef
275.
Sakane T, Akizuki M, Yamashita S, et al. The transport of a drug to the cerebrospinal fluid from the nasal cavity: the relation to the lipophilicity of the drug. Chem Pharm Bull (Tokyo) 1991; 39(9): 2456–8CrossRef
276.
Sakane T, Akizuki M, Taki Y, et al. Direct drug transport from the rat nasal cavity to the cerebrospinal fluid: the relation to the molecular weight of drugs. J Pharm Pharmacol 1995; 47: 379–81PubMedCrossRef
277.
278.
Washington N, McGlashan JA, Jackson SJ, et al. The effect of nasal patency on the clearance of radiolabeled saline in healthy volunteers. Pharm Res 2000; 17(6): 733–6PubMedCrossRef
279.
Bojsen-Moller F, Fahrenkrug J. Nasal swell bodies and cyclic changes in the air passage of the rat and rabbit nose. J Anat 1971; 110(1): 25–37PubMed
280.
Lowman HB, Chen YM, Skelton NJ, et al. Molecular mimics of insulin-like growth factor 1 (IGF-1) for inhibiting IGF-1: IGF-binding protein interactions. Biochemistry 1998; 37(25): 8870–8PubMedCrossRef
281.
Beglova N, LeSauteur L, Ekiel I, et al. Solution structure and internal motion of a bioactive peptide derived from nerve growth factor. J Biol Chem 1998; 273(37): 23652–8PubMedCrossRef
282.
Kaechi K, Furukawa Y, Ikegami R, et al. Pharmacological induction of physiologically active nerve growth factor in rat peripheral nervous system. J Pharmacol Exp Ther 1993; 264(1): 321–6PubMed
283.
Yamada K, Nitta A, Hasegawa T, et al. Orally active NGF synthesis stimulators: potential therapeutic agents in Alzheimer’s disease. Behav Brain Res 1997; 83(1-2): 117–22PubMedCrossRef
284.
Nitta A, Ogihara Y, Onishi J, et al. Propentofylline prevents neuronal dysfunction induced by infusion of anti-nerve growth factor antibody into the rat septum. Eur J Pharmacol 1996; 307(1): 1–6PubMedCrossRef
285.
Middlemiss PJ, Glasky AJ, Rathbone MP, et al. AIT-082, a unique purine derivative, enhances nerve growth factor mediated neurite outgrowth from PC12 cells. Neurosci Lett 1995; 199(2): 131–4PubMedCrossRef
286.
Rathbone MP, Middlemiss PJ, Gysbers JW, et al. Trophic effects of purines in neurons and glial cells. Prog Neurobiol 1999; 59(6): 663–90PubMedCrossRef
287.
Tirassa P, Aloe L, Stenfors C, et al. Cholecystokinin-8 protects central cholinergic neurons against fimbria-fornix lesion through the up-regulation of nerve growth factor synthesis. Proc Natl Acad Sci U S A 1999; 96(11): 6473–7PubMedCrossRef
288.
Snyder SH, Sabatini DM, Lai MM, et al. Neural actions of immunophilin ligands. Trends Pharmacol Sci 1998; 19(1): 21–6PubMedCrossRef
289.
Steiner JP, Hamilton GS, Ross DT, et al. Neurotrophic immunophilin ligands stimulate structural and functional recovery in neurodegenerative animal models. Proc Natl Acad Sci U S A 1997; 94(5): 2019–24PubMedCrossRef
290.
Costantini LC, Isacson O. Immunophilin ligands and GDNF enhance neurite branching or elongation from developing dopamine neurons in culture. Exp Neurol 2000; 164(1): 60–70PubMedCrossRef
291.
Sharkey J, Butcher SP. Immunophilins mediate the neuroprotective effects of FK506 in focal cerebral ischemia. Nature 1994; 371: 336–9PubMedCrossRef
292.
Poduslo JF, Curran GL, Gill JS. Putrescine-modified nerve growth factor: bioactivity, plasma pharmacokinetics, blood-brain/nerve barrier permeability, and nervous system biodistribution. J Neurochem 1998; 71(4): 1651–60PubMedCrossRef
293.
Martinez-Serrano A, Bjorklund A. Ex vivo nerve growth factor gene transfer to the basal forebrain in presymptomatic middle-aged rats prevents the development of cholinergic neuron atrophy and cognitive impairment during aging. Proc Natl Acad Sci U S A 1998; 95(4): 1858–63PubMedCrossRef
294.
Smith DE, Roberts J, Gage FH, et al. Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy. Proc Natl Acad Sci U S A 1999; 96(19): 10893–8PubMedCrossRef
295.
Tuszynski MH, Roberts J, Senut MC, et al. Gene therapy in the adult primate brain: intraparenchymal grafts of cells genetically modified to produce nerve growth factor prevent cholinergic neuronal degeneration. Gene Ther 1996; 3(4): 305–14PubMed
296.
297.
Verma IM, Somia N. Gene therapy: promises, problems and prospects. Nature 1997; 389: 239–42PubMedCrossRef
298.
Bachoud-Levi AC, Deglon N, Nguyen JP, et al. Neuroprotective gene therapy for Huntington’s disease using a polymer encapsulated BHK cell line engineered to secrete human CNTF. Hum Gene Ther 2000; 11(12): 1723–9PubMedCrossRef
299.
Meuli-Simmen C, Liu Y, Yeo TT, et al. Gene expression along the cerebral-spinal axis after regional gene delivery. Hum Gene Ther 1999; 10: 2689–700PubMedCrossRef
300.
Zhou LL, Huang L, Hayes RL, et al. Liposome-mediated NGF gene transfection following neuronal injury: Potential therapeutic applications. Gene Ther 1999; 6: 994–1005CrossRef
301.
Kordower JH, Emborg ME, Bloch J, et al. Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson’s disease. Science 2000; 290: 767–73PubMedCrossRef
302.
Mandir AS, Dawson VL, Dawson TM. Gene therapy to the rescue in Parkinson’s disease. Trends Pharmacol Sci 2001; 22: 103–5PubMedCrossRef
303.
304.
305.
Freed CR, Greene PE, Breeze RE, et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 2001; 344: 710–9PubMedCrossRef
306.
Hottinger AF, Aebischer P. Strategies for administering neurotrophic factors to the central nervous system. In: Hefti F, editor. Neurotrophic factors. Berlin: Springer-Verlag, 1999: 255–80CrossRef
307.
Zlokovic BV, Apuzzo ML. Cellular and molecular neurosurgery: pathways from concept to reality: part II. Vector systems and delivery methodologies for gene therapy of the central nervous system. Neurosurgery 1997; 40(4): 805–12PubMedCrossRef
Metadaten
Titel
Delivery of Neurotrophic Factors to the Central Nervous System
Pharmacokinetic Considerations
verfasst von
Robert G. Thorne
Dr William H. Frey II
Publikationsdatum
01.12.2001
Verlag
Springer International Publishing
Erschienen in
Clinical Pharmacokinetics / Ausgabe 12/2001
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200140120-00003