ArticleScientific reports2025
Neuroprotective effects of α-lipoic acid on ischemia/reperfusion injury in global cerebral ischemia mouse model.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Ischemia-reperfusion (I/R) injury, resulting from transient or permanent cerebral vessel occlusion, triggers oxidative stress, neuroinflammation, and blood-brain barrier (BBB) disruption, leading to progressive neuronal damage and cognitive decline. The hippocampus, due to its high metabolic demand and susceptibility to oxidative stress, is particularly vulnerable to I/R-induced injury. This study evaluated the neuroprotective effects of α-lipoic acid (α-LA), a potent antioxidant, using bilateral common carotid arteries occlusion/reperfusion (BCCAO/R) mouse model and an oxygen-glucose deprivation/reoxygenation in vitro model. In BCCAO/R mice, α-LA improved spatial memory without affecting motor activity and restored hippocampal tight junction proteins (Claudin-5 and Occludin) and antioxidant enzyme expression, indicating BBB stabilization and oxidative stress reduction. Although synaptic proteins (BDNF and PSD-95) were not restored, cognitive improvements suggest alternative protective mechanisms. In HT22 cells, α-LA decreased intracellular reactive oxygen species levels, enhanced viability, and inhibited apoptosis via decreased PARP cleavage and caspase-3 activation. These protective effects were linked to the activation of the Nrf2/ARE signaling pathway and the upregulation of its downstream antioxidant targets. Overall, α-LA demonstrated marked neuroprotective effects in ischemic models by reducing oxidative stress, preserving BBB integrity, and restoring hippocampal function, positioning it as a promising therapeutic candidate for ischemic brain injury.
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