nach oben

Acta Neuropathologica

Erschienen in:

01.07.2011 | Review

Brain microvascular pericytes in health and disease

verfasst von: Turgay Dalkara, Yasemin Gursoy-Ozdemir, Muge Yemisci

Erschienen in: Acta Neuropathologica | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

Pericytes are located at periphery of the microvessel wall and wrap it with their processes. They communicate with other cells of the neurovascular unit by direct contact or through signaling pathways and regulate several important microcirculatory functions. These include development and maintenance of the blood–brain barrier (BBB), distribution of the capillary blood flow to match the local metabolic need of the nearby cells, and angiogenesis. Pericytes also exhibit phagocytic activity and may function as pluripotent stem cells. Increasing evidence suggests a role for pericytes in a wide range of CNS diseases. They appear to be vulnerable to oxygen and nitrogen radical toxicity and have been shown to contract during cerebral ischemia and remain contracted despite reopening of the occluded artery. This causes impaired re-flow and may diminish the benefit of re-canalization therapies in stroke patients. Hyperglycemia-induced dysfunction of the signaling pathways between pericytes and endothelia is thought to play an important role in diabetic retinopathy, a common cause of blindness. Amyloid deposits detected within degenerating pericytes in the brains of patients with Alzheimer’s disease suggest that pericyte dysfunction may play a role in cerebral hypoperfusion and impaired amyloid β-peptide clearance in Alzheimer’s disease. This exciting possibility may reveal a novel temporal sequence of events in chronic neurodegeneration, in which microvascular dysfunction due to pericyte degeneration initiates secondary neurodegenerative changes. Identification of molecular mechanisms by which pericytes regulate BBB integrity in inflammatory conditions as well as in vasogenic brain edema may lead to new treatments. Pericytes may also take part in tissue repair and vascularization after CNS injury. In conclusion, although the evidence is just emerging and mostly preliminary, disclosing pericytes’ role in the pathophysiology of CNS diseases may yield exciting developments and novel treatments.

Abramsson A, Kurup S, Busse M, Yamada S, Lindblom P, Schallmeiner E, Stenzel D, Sauvaget D, Ledin J, Ringvall M, Landegren U, Kjellen L, Bondjers G, Li JP, Lindahl U, Spillmann D, Betsholtz C, Gerhardt H (2007) Defective N-sulfation of heparan sulfate proteoglycans limits PDGF-BB binding and pericyte recruitment in vascular development. Genes Dev 21:316–331PubMedCrossRef

Al Ahmad A, Gassmann M, Ogunshola OO (2009) Maintaining blood-brain barrier integrity: pericytes perform better than astrocytes during prolonged oxygen deprivation. J Cell Physiol 218:612–622PubMedCrossRef

Alliot F, Rutin J, Leenen PJ, Pessac B (1999) Pericytes and periendothelial cells of brain parenchyma vessels co-express aminopeptidase N, aminopeptidase A, and nestin. J Neurosci Res 58:367–378PubMedCrossRef

Armulik A, Genove G, Mae M, Nisancioglu MH, Wallgard E, Niaudet C, He L, Norlin J, Lindblom P, Strittmatter K, Johansson BR, Betsholtz C (2010) Pericytes regulate the blood-brain barrier. Nature 468:557–561PubMedCrossRef

Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA (2010) Glial and neuronal control of brain blood flow. Nature 468:232–243PubMedCrossRef

Bandopadhyay R, Orte C, Lawrenson JG, Reid AR, De Silva S, Allt G (2001) Contractile proteins in pericytes at the blood-brain and blood-retinal barriers. J Neurocytol 30:35–44PubMedCrossRef

Bell RD, Deane R, Chow N, Long X, Sagare A, Singh I, Streb JW, Guo H, Rubio A, Van Nostrand W, Miano JM, Zlokovic BV (2009) SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular cells. Nat Cell Biol 11:143–153PubMedCrossRef

Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R, Zlokovic BV (2010) Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron 68:409–427PubMedCrossRef

Bell RD, Zlokovic BV (2009) Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer’s disease. Acta Neuropathol 118:103–113PubMedCrossRef

10.

Bonkowski DKV, Balabanov RD, Borisov A, Dore-Duffy P (2011) The CNS microvascular pericyte: pericyte-astrocyte crosstalk in the regulation of tissue survival. Fluids Barriers CNS 18:8CrossRef

11.

Castejon OJ (1984) Submicroscopic changes of cortical capillary pericytes in human perifocal brain edema. J Submicrosc Cytol 16:601–618PubMed

12.

Chen Q, Anderson DR (1997) Effect of CO2 on intracellular pH and contraction of retinal capillary pericytes. Invest Ophthalmol Vis Sci 38:643–651PubMed

13.

Claudio L, Raine CS, Brosnan CF (1995) Evidence of persistent blood–brain barrier abnormalities in chronic-progressive multiple sclerosis. Acta Neuropathol 90:228–238PubMedCrossRef

14.

Cogan DG, Toussaint D, Kuwabara T (1961) Retinal vascular patterns. IV. Diabetic retinopathy. Arch Ophthalmol 66:366–378PubMed

15.

Daneman R, Zhou L, Kebede AA, Barres BA (2010) Pericytes are required for blood–brain barrier integrity during embryogenesis. Nature 468:562–566PubMedCrossRef

16.

de la Torre JC (2004) Is Alzheimer’s disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. Lancet Neurol 3:184–190PubMedCrossRef

17.

De Silva DA, Fink JN, Christensen S, Ebinger M, Bladin C, Levi CR, Parsons M, Butcher K, Barber PA, Donnan GA, Davis SM (2009) Assessing reperfusion and recanalization as markers of clinical outcomes after intravenous thrombolysis in the echoplanar imaging thrombolytic evaluation trial (EPITHET). Stroke 40:2872–2874PubMedCrossRef

18.

Dehouck MP, Vigne P, Torpier G, Breittmayer JP, Cecchelli R, Frelin C (1997) Endothelin-1 as a mediator of endothelial cell-pericyte interactions in bovine brain capillaries. J Cereb Blood Flow Metab 17:464–469PubMedCrossRef

19.

del Zoppo GJ, Mabuchi T (2003) Cerebral microvessel responses to focal ischemia. J Cereb Blood Flow Metab 23:879–894PubMedCrossRef

20.

Dore-Duffy P, Katychev A, Wang X, Van Buren E (2006) CNS microvascular pericytes exhibit multipotential stem cell activity. J Cereb Blood Flow Metab 26:613–624PubMedCrossRef

21.

Ejaz S, Chekarova I, Ejaz A, Sohail A, Lim CW (2008) Importance of pericytes and mechanisms of pericyte loss during diabetes retinopathy. Diabetes Obes Metab 10:53–63PubMed

22.

Enge M, Bjarnegard M, Gerhardt H, Gustafsson E, Kalen M, Asker N, Hammes HP, Shani M, Fassler R, Betsholtz C (2002) Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy. EMBO J 21:4307–4316PubMedCrossRef

23.

Fernandez-Klett F, Offenhauser N, Dirnagl U, Priller J, Lindauer U (2010) Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brain. Proc Natl Acad Sci USA 107:22290–22295PubMedCrossRef

24.

Frank RN, Dutta S, Mancini MA (1987) Pericyte coverage is greater in the retinal than in the cerebral capillaries of the rat. Invest Ophthalmol Vis Sci 28:1086–1091PubMed

25.

Garcia JH, Liu KF, Yoshida Y, Chen S, Lian J (1994) Brain microvessels: factors altering their patency after the occlusion of a middle cerebral artery (Wistar rat). Am J Pathol 145:728–740PubMed

26.

GE S, Song L, Pachter JS (2005) Where is the blood–brain barrier... really? J Neurosci Res 79:421–427PubMedCrossRef

27.

Geraldes P, Hiraoka-Yamamoto J, Matsumoto M, Clermont A, Leitges M, Marette A, Aiello LP, Kern TS, King GL (2009) Activation of PKC-delta and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy. Nat Med 15:1298–1306PubMedCrossRef

28.

Gerhardt H, Betsholtz C (2003) Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 314:15–23PubMedCrossRef

29.

Gerhardt H, Wolburg H, Redies C (2000) N-cadherin mediates pericytic-endothelial interaction during brain angiogenesis in the chicken. Dev Dyn 218:472–479PubMedCrossRef

30.

Gursoy-Ozdemir Y, Bolay H, Saribas O, Dalkara T (2000) Role of endothelial nitric oxide generation and peroxynitrite formation in reperfusion injury after focal cerebral ischemia. Stroke 31:1974–1980PubMedCrossRef

31.

Gursoy-Ozdemir Y, Can A, Dalkara T (2004) Reperfusion-induced oxidative/nitrative injury to neurovascular unit after focal cerebral ischemia. Stroke 35:1449–1453PubMedCrossRef

32.

Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D (2008) Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 359:1317–1329PubMedCrossRef

33.

Hamilton NB, Attwell D, Hall CN (2010) Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease. Front Neuroenergetics 2:5PubMed

34.

Hellstrom M, Gerhardt H, Kalen M, Li X, Eriksson U, Wolburg H, Betsholtz C (2001) Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol 153:543–553PubMedCrossRef

35.

Hellstrom M, Kalen M, Lindahl P, Abramsson A, Betsholtz C (1999) Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 126:3047–3055PubMed

36.

Ho KL (1985) Ultrastructure of cerebellar capillary hemangioblastoma. IV. Pericytes and their relationship to endothelial cells. Acta Neuropathol 67:254–264PubMedCrossRef

37.

Hossmann KA (2006) Pathophysiology and therapy of experimental stroke. Cell Mol Neurobiol 26:1057–1083PubMedCrossRef

38.

Iadecola C (2004) Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci 5:347–360PubMedCrossRef

39.

Iadecola C (2010) The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathol 120:287–296PubMedCrossRef

40.

Joyce NC, Haire MF, Palade GE (1985) Contractile proteins in pericytes. II. Immunocytochemical evidence for the presence of two isomyosins in graded concentrations. J Cell Biol 100:1387–1395PubMedCrossRef

41.

Kamouchi M, Ago T, Kitazono T (2011) Brain pericytes: emerging concepts and functional roles in brain homeostasis. Cell Mol Neurobiol 31:175–193

42.

Kamouchi M, Kitazono T, Ago T, Wakisaka M, Kuroda J, Nakamura K, Hagiwara N, Ooboshi H, Ibayashi S, Iida M (2007) Hydrogen peroxide-induced Ca²⁺ responses in CNS pericytes. Neurosci Lett 416:12–16PubMedCrossRef

43.

Kamouchi M, Kitazono T, Ago T, Wakisaka M, Ooboshi H, Ibayashi S, Iida M (2004) Calcium influx pathways in rat CNS pericytes. Brain Res Mol Brain Res 126:114–120PubMedCrossRef

44.

Kim JH, Yu YS, Kim DH, Kim KW (2009) Recruitment of pericytes and astrocytes is closely related to the formation of tight junction in developing retinal vessels. J Neurosci Res 87:653–659PubMedCrossRef

45.

Krueger M, Bechmann I (2010) CNS pericytes: concepts, misconceptions, and a way out. Glia 58:1–10PubMedCrossRef

46.

Le Beux YJ, Willemot J (1978) Actin- and myosin-like filaments in rat brain pericytes. Anat Rec 190:811–826PubMedCrossRef

47.

Lindahl P, Johansson BR, Leveen P, Betsholtz C (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277:242–245PubMedCrossRef

48.

Little JR, Kerr FW, Sundt TM Jr (1975) Microcirculatory obstruction in focal cerebral ischemia. Relationship to neuronal alterations. Mayo Clin Proc 50:264–270PubMed

49.

Liwnicz BH, Leach JL, Yeh HS, Privitera M (1990) Pericyte degeneration and thickening of basement membranes of cerebral microvessels in complex partial seizures: electron microscopic study of surgically removed tissue. Neurosurgery 26:409–420PubMedCrossRef

50.

Lo EH, Dalkara T, Moskowitz MA (2003) Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 4:399–415PubMedCrossRef

51.

Mathiisen TM, Lehre KP, Danbolt NC, Ottersen OP (2010) The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia 58:1094–1103PubMedCrossRef

52.

Nakamura K, Kamouchi M, Kitazono T, Kuroda J, Shono Y, Hagiwara N, Ago T, Ooboshi H, Ibayashi S, Iida M (2009) Amiloride inhibits hydrogen peroxide-induced Ca²⁺ responses in human CNS pericytes. Microvasc Res 77:327–334PubMedCrossRef

53.

Nehls V, Drenckhahn D (1991) Heterogeneity of microvascular pericytes for smooth muscle type alpha-actin. J Cell Biol 113:147–154PubMedCrossRef

54.

Ozerdem U, Stallcup WB (2003) Early contribution of pericytes to angiogenic sprouting and tube formation. Angiogenesis 6:241–249PubMedCrossRef

55.

Peppiatt CM, Howarth C, Mobbs P, Attwell D (2006) Bidirectional control of CNS capillary diameter by pericytes. Nature 443:700–704PubMedCrossRef

56.

Puro DG (2007) Physiology and pathobiology of the pericyte-containing retinal microvasculature: new developments. Microcirculation 14:1–10PubMedCrossRef

57.

Rouget C (1873) Memoiresurledeveloppement, lastructureetles proprietes physiologiques des capillaires sanguins et lymphatiques. Arch Physiol Norm Path 5:603–663

58.

Sato Y (1995) Activation of latent TGF-beta at the vascular wall—roles of endothelial cells and mural pericytes or smooth muscle cells. J Atheroscler Thromb 2:24–29PubMed

59.

Shepro D, Morel NM (1993) Pericyte physiology. FASEB J 7:1031–1038PubMed

60.

Sims DE (1986) The pericyte—a review. Tissue Cell 18:153–174PubMedCrossRef

61.

Sims DE (2000) Diversity within pericytes. Clin Exp Pharmacol Physiol 27:842–846PubMedCrossRef

62.

Skalli O, Pelte MF, Peclet MC, Gabbiani G, Gugliotta P, Bussolati G, Ravazzola M, Orci L (1989) Alpha-smooth muscle actin, a differentiation marker of smooth muscle cells, is present in microfilamentous bundles of pericytes. J Histochem Cytochem 37:315–321PubMedCrossRef

63.

Soares BP, Tong E, Hom J, Cheng SC, Bredno J, Boussel L, Smith WS, Wintermark M (2010) Reperfusion is a more accurate predictor of follow-up infarct volume than recanalization: a proof of concept using CT in acute ischemic stroke patients. Stroke 41:e34–e40PubMedCrossRef

64.

Szpak GM, Lewandowska E, Wierzba-Bobrowicz T, Bertrand E, Pasennik E, Mendel T, Stepien T, Leszczynska A, Rafalowska J (2007) Small cerebral vessel disease in familial amyloid and non-amyloid angiopathies: FAD-PS-1 (P117L) mutation and CADASIL. Immunohistochemical and ultrastructural studies. Folia Neuropathol 45:192–204PubMed

65.

Thomas WE (1999) Brain macrophages: on the role of pericytes and perivascular cells. Brain Res Brain Res Rev 31:42–57PubMedCrossRef

66.

Toribatake Y, Tomita K, Kawahara N, Baba H, Ohnari H, Tanaka S (1997) Regulation of vasomotion of arterioles and capillaries in the cat spinal cord: role of alpha actin and endothelin-1. Spinal Cord 35:26–32PubMedCrossRef

67.

Verbeek MM, de Waal RM, Schipper JJ, Van Nostrand WE (1997) Rapid degeneration of cultured human brain pericytes by amyloid beta protein. J Neurochem 68:1135–1141PubMedCrossRef

68.

Wahlgren N, Ahmed N, Davalos A, Ford GA, Grond M, Hacke W, Hennerici MG, Kaste M, Kuelkens S, Larrue V, Lees KR, Roine RO, Soinne L, Toni D, Vanhooren G (2007) Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 369:275–282PubMedCrossRef

69.

Wilhelmus MM, Otte-Holler I, van Triel JJ, Veerhuis R, Maat-Schieman ML, Bu G, de Waal RM, Verbeek MM (2007) Lipoprotein receptor-related protein-1 mediates amyloid-beta-mediated cell death of cerebrovascular cells. Am J Pathol 171:1989–1999PubMedCrossRef

70.

Winkler EA, Bell RD, Zlokovic BV (2010) Pericyte-specific expression of PDGF beta receptor in mouse models with normal and deficient PDGF beta receptor signaling. Mol Neurodegener 5:32PubMedCrossRef

71.

Wisniewski HM, Wegiel J, Wang KC, Lach B (1992) Ultrastructural studies of the cells forming amyloid in the cortical vessel wall in Alzheimer’s disease. Acta Neuropathol 84:117–127PubMedCrossRef

72.

Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T (2009) Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med 15:1031–1037PubMedCrossRef

73.

Zimmermann K (1923) Der feinere Bau der Blutkapillaren. Z Anat Entwicklungsgesch 68:29–109CrossRef

74.

Zlokovic BV (2010) Neurodegeneration and the neurovascular unit. Nat Med 16:1370–1371PubMedCrossRef

Titel: Brain microvascular pericytes in health and disease
verfasst von: Turgay Dalkara
Yasemin Gursoy-Ozdemir
Muge Yemisci
Publikationsdatum: 01.07.2011
Verlag: Springer-Verlag
Erschienen in: Acta Neuropathologica / Ausgabe 1/2011
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-011-0847-6

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

23.04.2024 | Demenz | Nachrichten

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Brain microvascular pericytes in health and disease

Abstract

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2011

Increased dopaminergic cells and protein aggregates in the olfactory bulb of patients with neurodegenerative disorders

The most common type of FTLD-FUS (aFTLD-U) is associated with a distinct clinical form of frontotemporal dementia but is not related to mutations in the FUS gene

Axonopathy is a compounding factor in the pathogenesis of Krabbe disease

Pathogenic T cell responses against aquaporin 4

A harmonized classification system for FTLD-TDP pathology

Pathological heterogeneity in amyotrophic lateral sclerosis with FUS mutations: two distinct patterns correlating with disease severity and mutation

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie