Long-term neuroprotection from a potent redox-modulating metalloporphyrin in the rat.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Sheng, H; Yang, W; Fukuda, S; Tse, HM; Paschen, W; Johnson, K; Batinic-Haberle, I; Crapo, JD; Pearlstein, RD; Piganelli, J; Warner, DS

Published Date

  • October 2009

Published In

Volume / Issue

  • 47 / 7

Start / End Page

  • 917 - 923

PubMed ID

  • 19631268

Pubmed Central ID

  • 19631268

Electronic International Standard Serial Number (EISSN)

  • 1873-4596

International Standard Serial Number (ISSN)

  • 0891-5849

Digital Object Identifier (DOI)

  • 10.1016/j.freeradbiomed.2009.05.039

Language

  • eng