Rat hippocampal CA3 neuronal injury induced by limb ischemia/reperfusion: A possible restorative effect of alpha lipoic acid.

Limb ischemia reperfusion (I/R) injury is associated with serious local and systemic effects. Reperfusion may augment tissue injury in excess of that produced by ischemia alone. The hippocampus has been reported to be vulnerable to I/R injury. Alpha lipoic acid (ALA) is an endogenous antioxidant with a powerful antioxidative, anti-inflammatory, and antiapoptotic properties. We studied the probable restorative effect of ALA on limb I/R-induced structural damage of rat hippocampus. Forty adult male albino rats were divided equally into four groups: group I (sham); group II (I/R-1 day) has undergone bilateral femoral arteries occlusion (3 h), then reperfusion for 1 day; group III (I/R-7 days) has undergone reperfusion for seven days; group IV (I/R-ALA) has undergone I/R as group III and received an intraperitoneal injection of ALA (100 mg/kg) for 7 days. I/R groups revealed degenerative changes in the pyramidal neuronal perikarya of CA3 field in the form of dark-stained cytoplasm, dilated RER cisternae, mitochondrial alterations, and dense bodies' accumulation. Their dendrites showed disorganized microtubules. Astrogliosis is featured by an increased number and increased immunoreactivity of astrocytes for glial fibrillary acid protein. Morphometric data revealed significant reduction of light neurons, surface area of neurons, and thickness of the CA3 layer. Most blood capillaries exhibited narrow lumen and irregular basal lamina. ALA ameliorated the neuronal damage. Pyramidal neurons revealed preservation of normal structure. Significant increase in the thickness of pyramidal layer in CA3 field and surface area and number of light neurons was observed but astrogliosis persisted. Limb I/R had a deleterious remote effect on the hippocampus aggravated with longer period of reperfusion. This work may encourage the use of ALA in the critical clinical settings with I/R injury.