Skip to main content
Erschienen in: Translational Stroke Research 2/2011

01.06.2011 | Original Article

Minocycline Development for Acute Ischemic Stroke

verfasst von: Susan C. Fagan, Lydia E. Cronic, David C. Hess

Erschienen in: Translational Stroke Research | Ausgabe 2/2011

Einloggen, um Zugang zu erhalten

Abstract

Minocycline, a tetracycline antibiotic, has shown anti-inflammatory, anti-apoptotic, and neuroprotective effects in many models of cerebral ischemia and neurodegenerative disease. Its high penetration of the blood–brain barrier, good safety profile, and delayed therapeutic window make it an ideal candidate for use in stroke. In animal models, minocycline reduced infarct size and improved neurologic outcome when administered acutely, with similar neuroprotective benefits seen following delayed administration. To date, two early phase clinical trials have shown minocycline to be safe and potentially effective in acute ischemic stroke, alone or in combination with tissue plasminogen activator. A large efficacy clinical trial is now needed to confirm previous studies, allow for subgroup analysis, and pinpoint the potential place for minocycline in acute stroke therapy.
Literatur
1.
Zurück zum Zitat Matsukawa N, Yasuhara T, Hara K, Xu L, Maki M, Yu G, et al. Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke. BMC Neurosci. 2009;10(1):126.PubMedCrossRef Matsukawa N, Yasuhara T, Hara K, Xu L, Maki M, Yu G, et al. Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke. BMC Neurosci. 2009;10(1):126.PubMedCrossRef
2.
Zurück zum Zitat Kleindorfer D, Xu Y, Moomaw CJ, Khatri P, Adeoye O, Hornung R. US geographic distribution of rt-PA utilization by hospital for acute ischemic stroke. Stroke. 2009;40(11):3580–4.PubMedCrossRef Kleindorfer D, Xu Y, Moomaw CJ, Khatri P, Adeoye O, Hornung R. US geographic distribution of rt-PA utilization by hospital for acute ischemic stroke. Stroke. 2009;40(11):3580–4.PubMedCrossRef
3.
Zurück zum Zitat Saivin S, Houin G. Clinical pharmacokinetics of doxycycline and minocycline. Clin Pharmacokinet. 1988;15(6):355–66.PubMedCrossRef Saivin S, Houin G. Clinical pharmacokinetics of doxycycline and minocycline. Clin Pharmacokinet. 1988;15(6):355–66.PubMedCrossRef
4.
Zurück zum Zitat Coskey R. Acne: treatment with minocycline. Cutis. 1976;17(4):799–801.PubMed Coskey R. Acne: treatment with minocycline. Cutis. 1976;17(4):799–801.PubMed
5.
Zurück zum Zitat Tilley BC, Alarcon GS, Heyse SP, Trentham DE, Neuner R, Kaplan DA, et al. Minocycline in rheumatoid arthritis: a 48-week, double-blind, placebo-controlled trial. Ann Intern Med. 1995;122(2):81–9.PubMed Tilley BC, Alarcon GS, Heyse SP, Trentham DE, Neuner R, Kaplan DA, et al. Minocycline in rheumatoid arthritis: a 48-week, double-blind, placebo-controlled trial. Ann Intern Med. 1995;122(2):81–9.PubMed
6.
Zurück zum Zitat Yrjänheikki J, Keinänen R, Pellikka M, Hökfelt T, Koistinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA. 1998;95(26):15769–74.PubMedCrossRef Yrjänheikki J, Keinänen R, Pellikka M, Hökfelt T, Koistinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA. 1998;95(26):15769–74.PubMedCrossRef
7.
Zurück zum Zitat Yrjänheikki J, Tikka T, Keinänen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci USA. 1999;96(23):13496–500.PubMedCrossRef Yrjänheikki J, Tikka T, Keinänen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci USA. 1999;96(23):13496–500.PubMedCrossRef
8.
Zurück zum Zitat Lin S, Zhang Y, Dodel R, Farlow MR, Paul SM, Du Y. Minocycline blocks nitric oxide-induced neurotoxicity by inhibition p38 MAP kinase in rat cerebellar granule neurons. Neurosci Lett. 2001;315(1–2):61–4.PubMedCrossRef Lin S, Zhang Y, Dodel R, Farlow MR, Paul SM, Du Y. Minocycline blocks nitric oxide-induced neurotoxicity by inhibition p38 MAP kinase in rat cerebellar granule neurons. Neurosci Lett. 2001;315(1–2):61–4.PubMedCrossRef
9.
Zurück zum Zitat Zhu S, Stavrovskaya IG, Drozda M, Kim BYS, Ona V, Li M, et al. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature. 2002;417(6884):74–8. doi:10.1038/417074a.PubMedCrossRef Zhu S, Stavrovskaya IG, Drozda M, Kim BYS, Ona V, Li M, et al. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature. 2002;417(6884):74–8. doi:10.​1038/​417074a.PubMedCrossRef
10.
Zurück zum Zitat Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci. 2001;21(8):2580–8.PubMed Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci. 2001;21(8):2580–8.PubMed
11.
Zurück zum Zitat He Y, Appel S, Le W. Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res. 2001;909(1–2):187–93.PubMedCrossRef He Y, Appel S, Le W. Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res. 2001;909(1–2):187–93.PubMedCrossRef
12.
Zurück zum Zitat Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, et al. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci. 2002;22(5):1763–71.PubMed Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, et al. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci. 2002;22(5):1763–71.PubMed
13.
Zurück zum Zitat Sanchez Mejia RO, Ona VO, Li M, Friedlander RM. Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction. Neurosurgery. 2001;48(6):1393–401.PubMed Sanchez Mejia RO, Ona VO, Li M, Friedlander RM. Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction. Neurosurgery. 2001;48(6):1393–401.PubMed
14.
Zurück zum Zitat Alano CC, Kauppinen TM, Valls AV, Swanson RA. Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations. Proc Natl Acad Sci. 2006;103(25):9685–90.PubMedCrossRef Alano CC, Kauppinen TM, Valls AV, Swanson RA. Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations. Proc Natl Acad Sci. 2006;103(25):9685–90.PubMedCrossRef
15.
Zurück zum Zitat Machado L, Kozak A, Ergul A, Hess D, Borlongan C, Fagan S. Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke. BMC Neurosci. 2006;7(1):56.PubMedCrossRef Machado L, Kozak A, Ergul A, Hess D, Borlongan C, Fagan S. Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke. BMC Neurosci. 2006;7(1):56.PubMedCrossRef
16.
Zurück zum Zitat Elewa H, Hilali H, Hess D, Machado L, Fagan S. Minocycline for short-term neuroprotection. Pharmacotherapy. 2006;26(4):15–21.CrossRef Elewa H, Hilali H, Hess D, Machado L, Fagan S. Minocycline for short-term neuroprotection. Pharmacotherapy. 2006;26(4):15–21.CrossRef
17.
Zurück zum Zitat Du Y, Ma Z, Lin S, Dodel RC, Gao F, Bales KR, et al. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. Proc Natl Acad Sci USA. 2001;98(25):14669–74.PubMedCrossRef Du Y, Ma Z, Lin S, Dodel RC, Gao F, Bales KR, et al. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. Proc Natl Acad Sci USA. 2001;98(25):14669–74.PubMedCrossRef
18.
Zurück zum Zitat Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, et al. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med. 2000;6(7):797–801. doi:10.1038/77528.PubMedCrossRef Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, et al. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med. 2000;6(7):797–801. doi:10.​1038/​77528.PubMedCrossRef
19.
Zurück zum Zitat Wang C, Yang T, Noor R, Shuaib A. Delayed minocycline but not delayed mild hypothermia protects against embolic stroke. BMC Neurol. 2002;2(1):2.PubMedCrossRef Wang C, Yang T, Noor R, Shuaib A. Delayed minocycline but not delayed mild hypothermia protects against embolic stroke. BMC Neurol. 2002;2(1):2.PubMedCrossRef
20.
Zurück zum Zitat Arvin KL, Han BH, Du Y, Lin S-Z, Paul SM, Holtzman DM. Minocycline markedly protects the neonatal brain against hypoxic–ischemic injury. Ann Neurol. 2002;52(1):54–61.PubMedCrossRef Arvin KL, Han BH, Du Y, Lin S-Z, Paul SM, Holtzman DM. Minocycline markedly protects the neonatal brain against hypoxic–ischemic injury. Ann Neurol. 2002;52(1):54–61.PubMedCrossRef
21.
Zurück zum Zitat Wang CX, Yang T, Shuaib A. Effects of minocycline alone and in combination with mild hypothermia in embolic stroke. Brain Res. 2003;963(1–2):327–9.PubMedCrossRef Wang CX, Yang T, Shuaib A. Effects of minocycline alone and in combination with mild hypothermia in embolic stroke. Brain Res. 2003;963(1–2):327–9.PubMedCrossRef
22.
Zurück zum Zitat Wells JEA, Hurlbert RJ, Fehlings MG, Yong VW. Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice. Brain. 2003;126(7):1628–37.PubMedCrossRef Wells JEA, Hurlbert RJ, Fehlings MG, Yong VW. Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice. Brain. 2003;126(7):1628–37.PubMedCrossRef
23.
Zurück zum Zitat Power C, Henry S, Del Bigio MR, Larsen PH, Corbett D, Imai Y, et al. Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases. Ann Neurol. 2003;53(6):731–42.PubMedCrossRef Power C, Henry S, Del Bigio MR, Larsen PH, Corbett D, Imai Y, et al. Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases. Ann Neurol. 2003;53(6):731–42.PubMedCrossRef
24.
Zurück zum Zitat Nagel S, Su Y, Horstmann S, Heiland S, Gardner H, Koziol J, et al. Minocycline and hypothermia for reperfusion injury after focal cerebral ischemia in the rat—effects on BBB breakdown and MMP expression in the acute and subacute phase. Brain Res. 2008;1188:198–206.PubMedCrossRef Nagel S, Su Y, Horstmann S, Heiland S, Gardner H, Koziol J, et al. Minocycline and hypothermia for reperfusion injury after focal cerebral ischemia in the rat—effects on BBB breakdown and MMP expression in the acute and subacute phase. Brain Res. 2008;1188:198–206.PubMedCrossRef
25.
Zurück zum Zitat Zhang W, Narayanan M, Friedlander RM. Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS. Ann Neurol. 2003;53(2):267–70.PubMedCrossRef Zhang W, Narayanan M, Friedlander RM. Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS. Ann Neurol. 2003;53(2):267–70.PubMedCrossRef
26.
Zurück zum Zitat Ravina BM, Fagan SC, Hart RG, Hovinga CA, Murphy DD, Dawson TM, Marler JR. Neuroprotective agents for clinical trials in Parkinson’s disease: a systematic assessment. Neurology. 2003;60(8):1234–40.PubMed Ravina BM, Fagan SC, Hart RG, Hovinga CA, Murphy DD, Dawson TM, Marler JR. Neuroprotective agents for clinical trials in Parkinson’s disease: a systematic assessment. Neurology. 2003;60(8):1234–40.PubMed
27.
Zurück zum Zitat Kim H-S, Suh Y-H. Minocycline and neurodegenerative diseases. Behav Brain Res. 2009;196(2):168–79.PubMedCrossRef Kim H-S, Suh Y-H. Minocycline and neurodegenerative diseases. Behav Brain Res. 2009;196(2):168–79.PubMedCrossRef
28.
Zurück zum Zitat Parashos SA, Swearingen CJ, Biglan KM, Bodis-Wollner I, Liang GS, Ross GW, et al. Determinants of the timing of symptomatic treatment in early Parkinson disease: The National Institutes of Health Exploratory Trials in Parkinson disease (NET-PD) experience. Arch Neurol. 2009;66(9):1099–104.PubMedCrossRef Parashos SA, Swearingen CJ, Biglan KM, Bodis-Wollner I, Liang GS, Ross GW, et al. Determinants of the timing of symptomatic treatment in early Parkinson disease: The National Institutes of Health Exploratory Trials in Parkinson disease (NET-PD) experience. Arch Neurol. 2009;66(9):1099–104.PubMedCrossRef
29.
Zurück zum Zitat Gordon PH, Gelinas DF, Qualls C, Meister ME, Werner J, Mendoza M, et al. Placebo controlled phase I/II studies of minocycline in amyotrophic lateral sclerosis. Neurology. 2004;62(10):1845–7.PubMed Gordon PH, Gelinas DF, Qualls C, Meister ME, Werner J, Mendoza M, et al. Placebo controlled phase I/II studies of minocycline in amyotrophic lateral sclerosis. Neurology. 2004;62(10):1845–7.PubMed
30.
Zurück zum Zitat Xu L, Fagan SC, Waller J, Edwards D, Borlongan C, Zheng J, et al. Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats. BMC Neurol. 2004;4(1):7.PubMedCrossRef Xu L, Fagan SC, Waller J, Edwards D, Borlongan C, Zheng J, et al. Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats. BMC Neurol. 2004;4(1):7.PubMedCrossRef
31.
Zurück zum Zitat Fagan SC, Waller JL, Nichols FT, Edwards DJ, Pettigrew LC, Clark WM, et al. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. Stroke. 2010;41(10):2283–7.PubMedCrossRef Fagan SC, Waller JL, Nichols FT, Edwards DJ, Pettigrew LC, Clark WM, et al. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. Stroke. 2010;41(10):2283–7.PubMedCrossRef
32.
Zurück zum Zitat Hayakawa K, Mishima K, Nozako M, Hazekawa M, Mishima S, Fujioka M, et al. Delayed treatment with minocycline ameliorates neurologic impairment through activated microglia expressing a high-mobility group box1-inhibiting mechanism. Stroke. 2008;39(3):951–8.PubMedCrossRef Hayakawa K, Mishima K, Nozako M, Hazekawa M, Mishima S, Fujioka M, et al. Delayed treatment with minocycline ameliorates neurologic impairment through activated microglia expressing a high-mobility group box1-inhibiting mechanism. Stroke. 2008;39(3):951–8.PubMedCrossRef
33.
Zurück zum Zitat Liu Z, Fan Y, Won SJ, Neumann M, Hu D, Zhou L, et al. Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia. Stroke. 2007;38(1):146–52.PubMedCrossRef Liu Z, Fan Y, Won SJ, Neumann M, Hu D, Zhou L, et al. Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia. Stroke. 2007;38(1):146–52.PubMedCrossRef
34.
Zurück zum Zitat Hewlett KA, Corbett D. Delayed minocycline treatment reduces long-term functional deficits and histological injury in a rodent model of focal ischemia. Neuroscience. 2006;141(1):27–33.PubMedCrossRef Hewlett KA, Corbett D. Delayed minocycline treatment reduces long-term functional deficits and histological injury in a rodent model of focal ischemia. Neuroscience. 2006;141(1):27–33.PubMedCrossRef
35.
Zurück zum Zitat Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, et al. Minocycline treatment in acute stroke. Neurology. 2007;69(14):1404–10.PubMedCrossRef Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, et al. Minocycline treatment in acute stroke. Neurology. 2007;69(14):1404–10.PubMedCrossRef
36.
Zurück zum Zitat Wang J, Wei Q, Wang C-Y, Hill WD, Hess DC, Dong Z. Minocycline up-regulates Bcl-2 and protects against cell death in mitochondria. J Biol Chem. 2004;279(19):19948–54.PubMedCrossRef Wang J, Wei Q, Wang C-Y, Hill WD, Hess DC, Dong Z. Minocycline up-regulates Bcl-2 and protects against cell death in mitochondria. J Biol Chem. 2004;279(19):19948–54.PubMedCrossRef
37.
Zurück zum Zitat Colovic M, Caccia S. Liquid chromatographic determination of minocycline in brain-to-plasma distribution studies in the rat. J Chromatogr B. 2003;791(1–2):337–43.CrossRef Colovic M, Caccia S. Liquid chromatographic determination of minocycline in brain-to-plasma distribution studies in the rat. J Chromatogr B. 2003;791(1–2):337–43.CrossRef
38.
Zurück zum Zitat Drew TM, Altman R, Black K, Goldfield M. Minocycline for prophylaxis of infection with Neisseria meningitidis: high rate of side effects in recipients. J Infect Dis. 1976;133(2):194–8.PubMedCrossRef Drew TM, Altman R, Black K, Goldfield M. Minocycline for prophylaxis of infection with Neisseria meningitidis: high rate of side effects in recipients. J Infect Dis. 1976;133(2):194–8.PubMedCrossRef
39.
Zurück zum Zitat Clark BJ, Dornbush AC, Hutchinson J. Minocycline administered intravenously: pharmacological activity and clinical experience. Curr Ther Res. 1974;16(9):865–77.PubMed Clark BJ, Dornbush AC, Hutchinson J. Minocycline administered intravenously: pharmacological activity and clinical experience. Curr Ther Res. 1974;16(9):865–77.PubMed
40.
Zurück zum Zitat Murata Y, Rosell A, Scannevin RH, Rhodes KJ, Wang X, Lo EH. Extension of the thrombolytic time window with minocycline in experimental stroke. Stroke; Journal Cerebral Circulation. 2008;39(12):3372–7. Murata Y, Rosell A, Scannevin RH, Rhodes KJ, Wang X, Lo EH. Extension of the thrombolytic time window with minocycline in experimental stroke. Stroke; Journal Cerebral Circulation. 2008;39(12):3372–7.
41.
Zurück zum Zitat Machado LS, Sazonova IY, Kozak A, Wiley DC, El-Remessy AB, Ergul A, et al. Minocycline and tissue-type plasminogen activator for stroke: assessment of interaction potential. Stroke. 2009;40(9):3028–33. Machado LS, Sazonova IY, Kozak A, Wiley DC, El-Remessy AB, Ergul A, et al. Minocycline and tissue-type plasminogen activator for stroke: assessment of interaction potential. Stroke. 2009;40(9):3028–33.
42.
Zurück zum Zitat Fukuda S, Fini CA, Mabuchi T, Koziol JA, Eggleston Jr LL, del Zoppo GJ. Focal cerebral ischemia induces active proteases that degrade microvascular matrix. Stroke. 2004;35(4):998–1004.PubMedCrossRef Fukuda S, Fini CA, Mabuchi T, Koziol JA, Eggleston Jr LL, del Zoppo GJ. Focal cerebral ischemia induces active proteases that degrade microvascular matrix. Stroke. 2004;35(4):998–1004.PubMedCrossRef
43.
Zurück zum Zitat Rosenberg GA, Navratil M, Barone F, Feuerstein G. Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. J Cereb Blood Flow Metab. 1996;16(3):360–6.PubMedCrossRef Rosenberg GA, Navratil M, Barone F, Feuerstein G. Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. J Cereb Blood Flow Metab. 1996;16(3):360–6.PubMedCrossRef
44.
Zurück zum Zitat Heo JH, Lucero J, Abumiya T, Koziol JA, Copeland BR, del Zoppo GJ. Matrix metalloproteinases increase very early during experimental focal cerebral Ischemia. J Cereb Blood Flow Metab. 1999;19(6):624–33.PubMedCrossRef Heo JH, Lucero J, Abumiya T, Koziol JA, Copeland BR, del Zoppo GJ. Matrix metalloproteinases increase very early during experimental focal cerebral Ischemia. J Cereb Blood Flow Metab. 1999;19(6):624–33.PubMedCrossRef
45.
Zurück zum Zitat Gasche Y, Fujimura M, Morita-Fujimura Y, Copin J-C, Kawase M, Massengale J, et al. Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood–brain barrier dysfunction. J Cereb Blood Flow Metab. 1999;19(9):1020–8.PubMedCrossRef Gasche Y, Fujimura M, Morita-Fujimura Y, Copin J-C, Kawase M, Massengale J, et al. Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood–brain barrier dysfunction. J Cereb Blood Flow Metab. 1999;19(9):1020–8.PubMedCrossRef
46.
Zurück zum Zitat Weng YC, Kriz J. Differential neuroprotective effects of a minocycline-based drug cocktail in transient and permanent focal cerebral ischemia. Exp Neurol. 2007;204(1):433–42.PubMedCrossRef Weng YC, Kriz J. Differential neuroprotective effects of a minocycline-based drug cocktail in transient and permanent focal cerebral ischemia. Exp Neurol. 2007;204(1):433–42.PubMedCrossRef
47.
Zurück zum Zitat Sathasivam S, Grierson AJ, Shaw PJ. Characterization of the caspase cascade in a cell culture model of SOD1-related familial amyotrophic lateral sclerosis: expression, activation and therapeutic effects of inhibition. Neuropathol Appl Neurobiol. 2005;31(5):467–85.PubMedCrossRef Sathasivam S, Grierson AJ, Shaw PJ. Characterization of the caspase cascade in a cell culture model of SOD1-related familial amyotrophic lateral sclerosis: expression, activation and therapeutic effects of inhibition. Neuropathol Appl Neurobiol. 2005;31(5):467–85.PubMedCrossRef
48.
Zurück zum Zitat Kasner SE. Clinical interpretation and use of stroke scales. Lancet Neurol. 2006;5(7):603–12.PubMedCrossRef Kasner SE. Clinical interpretation and use of stroke scales. Lancet Neurol. 2006;5(7):603–12.PubMedCrossRef
49.
Zurück zum Zitat Tilley BC, Marler J, Geller NL, Lu M, Legler J, Brott T, et al. Use of a global test for multiple outcomes in stroke trials with application to the National Institute of Neurological Disorders and Stroke t-PA Stroke Trial. Stroke. 1996;27(11):2136–42.PubMed Tilley BC, Marler J, Geller NL, Lu M, Legler J, Brott T, et al. Use of a global test for multiple outcomes in stroke trials with application to the National Institute of Neurological Disorders and Stroke t-PA Stroke Trial. Stroke. 1996;27(11):2136–42.PubMed
50.
Zurück zum Zitat Li J, McCullough LD. Sex differences in minocycline-induced neuroprotection after experimental stroke. J Cereb Blood Flow Metab. 2009;29(4):670–4.PubMedCrossRef Li J, McCullough LD. Sex differences in minocycline-induced neuroprotection after experimental stroke. J Cereb Blood Flow Metab. 2009;29(4):670–4.PubMedCrossRef
Metadaten
Titel
Minocycline Development for Acute Ischemic Stroke
verfasst von
Susan C. Fagan
Lydia E. Cronic
David C. Hess
Publikationsdatum
01.06.2011
Verlag
Springer-Verlag
Erschienen in
Translational Stroke Research / Ausgabe 2/2011
Print ISSN: 1868-4483
Elektronische ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-011-0072-6

Weitere Artikel der Ausgabe 2/2011

Translational Stroke Research 2/2011 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Wartezeit nicht kürzer, aber Arbeit flexibler

Psychotherapie Medizin aktuell

Fünf Jahren nach der Neugestaltung der Psychotherapie-Richtlinie wurden jetzt die Effekte der vorgenommenen Änderungen ausgewertet. Das Hauptziel der Novellierung war eine kürzere Wartezeit auf Therapieplätze. Dieses Ziel wurde nicht erreicht, es gab jedoch positive Auswirkungen auf andere Bereiche.

„Restriktion auf vier Wochen Therapie bei Schlaflosigkeit ist absurd!“

06.05.2024 Insomnie Nachrichten

Chronische Insomnie als eigenständiges Krankheitsbild ernst nehmen und adäquat nach dem aktuellen Forschungsstand behandeln: Das forderte der Schlafmediziner Dr. Dieter Kunz von der Berliner Charité beim Praxis Update.

Stuhltransfusion könnte Fortschreiten von Parkinson-Symptomen bremsen

03.05.2024 Parkinson-Krankheit Nachrichten

Kann eine frühzeitige Stuhltransplantation das Fortschreiten von Parkinson-Symptomen verlangsamen? Die Ergebnisse einer randomisierten Phase-2-Studie scheinen dafür zu sprechen.

Frühe Tranexamsäure-Therapie nützt wenig bei Hirnblutungen

02.05.2024 Hirnblutung Nachrichten

Erhalten Personen mit einer spontanen Hirnblutung innerhalb von zwei Stunden nach Symptombeginn eine Tranexamsäure-Therapie, kann dies weder die Hämatomexpansion eindämmen noch die Mortalität senken.

Update Neurologie

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