Published Online
on February 1, 2007

A more recent version of this article appeared on March 1, 2007

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Submitted on August 23, 2006
Revised on October 2, 2006
Accepted on October 12, 2006

Lecithinized Superoxide Dismutase Improves Outcomes and Attenuates Focal Cerebral Ischemic Injury via Antiapoptotic Mechanisms in Rats

Tamiji Tsubokawa MD, PhD; Vikram Jadhav MB, BS, PhD; Ihsan Solaroglu MD; Yoshiaki Shiokawa MD, PhD; Yoshifumi Konishi MD, PhD; and John H. Zhang MD, PhD^*

From the Departments of Physiology and Pharmacology (T.T., V.J., I.S., J.Z.), Neurosurgery (J.Z.), and Anesthesiology (J.Z.), Loma Linda University School of Medicine, Loma Linda, Calif, and the Department of Neurosugery (Y.S., Y.K.), Kyorin University School of Medicine, Tokyo, Japan.

^* To whom correspondence should be addressed. E-mail: johnzhang3910{at}yahoo.com.

Background and Purpose--Recent studies have shown the antiapoptotic neuroprotective effects of lecithinized superoxide dismutase (PC-SOD) in different forms of brain injury. We tested the effects of PC-SOD in focal cerebral ischemia in the rat middle cerebral artery occlusion model (MCAO).

Methods--Adult male Sprague-Dawley rats were treated with PC-SOD (0.3, 1.0, and 3.0 mg/kg) administered intravenously after 90 minutes of occlusion (beginning of reperfusion). Physiological parameters, neurological score, and infarct volume were assessed at 24 and 72 hours in 3 groups of animals: sham-operated (n=18), MCAO treated with vehicle (n=26), and MCAO treated with PC-SOD (n=37). Oxidative stress was evaluated by malondialdehyde assay, and the apoptotic mechanisms were studied by Western blotting.

Results--PC-SOD treatment significantly reduced infarct volume and improved neurological scores at different time points compared with the vehicle-treated group. PC-SOD treatment decreased malondialdehyde levels, cytochrome c, and cleaved caspase 3 expression and increased mitochondrial Bcl-2 expression.

Conclusions--Inhibition of oxidative stress with PC-SOD treatment improves outcomes after focal cerebral ischemia. This neuroprotective effect is likely exerted by antiapoptotic mechanisms.

Key words: cerebral ischemia • lecithinized superoxide dismutase • neuronal apoptosis • oxidative stress

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