Abstract T P82: Long-Term Neurorestorative Effect of α-lipoic Acid Treatment in Focal Cerebral Ischemia Model

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Introduction: A considerable body of evidence suggests that oxidative stress is a fundamental mechanism of brain damage in stroke. A recent study suggests that the antioxidant properties of alpha-lipoic acid (aLA) correlate with its ability to promote neuroproliferation. However, there have been no reports of comprehensive studies examining the neurorestorative effects of aLA administered after the onset of ischemia. Hypothesis: The neuroprotective effects of acute treatment with ALA on neuroproliferation and long-term functional recovery following cerebral ischemic injury were examined using an animal model of clinical stroke with middle cerebral artery occlusion (MCAO). Methods: The middle cerebral artery (MCA) of adult male Sprague-Dawley rats was occluded for 2 h and then reperfused. To examine the effect of ALA on brain infarction, ALA (20 mg/kg body weight) was administered after the induction of anesthesia in 71 animals (ALA group) through the left external jugular vein immediately after reperfusion of the left MCAO. An equivalent volume of vehicle was administrated to 71 animals (control group) using the same procedure. A neurologic examination was performed at defined points after MCAO and a neurological deficit score (NDS) was obtained. Motor impairment was assessed by the accelerating rotarod test. Levels of endogenous neural precursor and glial cell were analyzed by immunohistochemistry. Results: Immediate aLA administration group after reperfusion significantly reduced the mortality, infarct size, and NDS than control group (n=71, P=0.005, P=0.002, and P=0.001, respectively). Long-term functional outcomes by Rotarod test were also markedly improved by aLA treatment (P=0.013). After 7 and 14 days of treatment, significantly more cells were labeled with BrdU, nestin, and GFAP in the aLA-treated rats along the infarct and infarct core regions. Significantly more BrdU/GFAP double-labeled cells were observed in the subventricular zone of the aLA group on days 7 and 14. Conclusions: These results indicate that urgent treatment with aLA after ischemic injury may have significant neurorestorative effects through enhanced neuroproliferation. aLA may be a useful intervention for the treatment of acute ischemic stroke.