Long-term neuroprotection from a potent redox-modulating metalloporphyrin in the rat
| Autor: | Shiro Fukuda, Wulf Paschen, Huaxin Sheng, David S. Warner, Wei Yang, Kwame Johnson, Jon D. Piganelli, James D. Crapo, Hubert M. Tse, Robert D. Pearlstein, Ines Batinic-Haberle |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Metalloporphyrins Ischemia medicine.disease_cause Biochemistry Aconitase Neuroprotection Drug Administration Schedule Article Neurologic function Physiology (medical) Ischemic insult Medicine Animals Middle cerebral artery occlusion Rats Wistar Aconitate Hydratase Dose-Response Relationship Drug business.industry NF-kappa B Infarction Middle Cerebral Artery Infarct size medicine.disease Rats Disease Models Animal Oxidative Stress Neuroprotective Agents Treatment Outcome Anesthesia business Oxidation-Reduction Oxidative stress |
| Zdroj: | Free radical biologymedicine. 47(7) |
| ISSN: | 1873-4596 |
| Popis: | Sustained oxidative stress is a known sequel to focal cerebral ischemia. This study examined the effects of treatment with a single dose or sustained infusion of the redox-modulating MnPorphyrin Mn(III)TDE-2-ImP(5+) on outcome from middle cerebral artery occlusion (MCAO) in the rat. Normothermic rats were subjected to 90 min MCAO followed by 90 min reperfusion and then were treated with a single intracerebroventricular dose of Mn(III)TDE-2-ImP(5+). Neurologic and histologic outcomes were assessed at 1 or 8 weeks postischemia. A single dose of Mn(III)TDE-2-ImP(5+) caused a dose-dependent improvement in histologic and neurologic outcome when assessed 1 week postischemia. Mn(III)TDE-2-ImP(5+) afforded preservation of brain aconitase activity at 5.5 h after reperfusion onset, consistent with its known antioxidant properties. Mn(III)TDE-2-ImP(5+) also attenuated postischemic NF-kappaB activation. Evidence for effects on cerebral infarct size and neurologic function had completely dissipated when rats were allowed to survive for 8 weeks postischemia. In contrast, a 1-week continuous intracerebroventricular Mn(III)TDE-2-ImP(5+) infusion caused persistent and substantive reduction in both cerebral infarct size and neurologic deficit at 8 weeks postischemia. Pharmacologic modulation of postischemic oxidative stress is likely to require sustained intervention for enduring efficacy in improving neurologic and histologic outcome from a transient focal ischemic insult. |
| Databáze: | OpenAIRE |
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