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

Abstract

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.

Lipid metabolism in astrocytic structure and function

“…Conjugated linoleic acid has been shown to alter the levels of TNF-α, IL-1β, and RANTES in cultured human astrocytes [192]. Within the context of ischemia, intravenous injection of α-lipoic acid reduced neuronal damage in a rat model of ischemia but did not reduce astrogliosis [193].…”

Effects of Lipoic Acid on Ischemia‐Reperfusion Injury

“…LA treatment also attenuated the injuries of other tissues caused by limb I/R. A recent study [ 100 ] showed that limb I/R induced the degenerative injury of rat hippocampal CA3 neurons (e.g., the reduction of light neuron number, surface areas of neurons, and the thickness of the CA3 layer together with increased capillary lesions), and an injection of LA (100 mg/kg, i.p) for 7 d significantly ameliorated these damages. The result indicated the potential application of LA in both nervous system and peripheral tissues simultaneously induced by limb I/R.…”

Tao‐Hong‐Si‐Wu decoction reduces ischemia reperfusion rat myoblast cells calcium overloading and inflammation through the Wnt/IP3R/CAMKII pathway

“…Limb ischemia reperfusion injury (LIRI) is a combination of limb ischemia injury and reperfusion injury, which is a common and complicated pathological process after severe clinical trauma with high morbidity and mortality. 1 Replantation of severed limb, crush injury, thrombosis of lower extremities, repair of abdominal aortic aneurysm, and traumatic arterial injury are the main causes of LIRI which can not only damage the local tissues of the limbs, but also affect the distal viscera. 2 The pathological mechanisms of limb ischemia-reperfusion injury are considered to include oxygen free radicals, lipid peroxidation, excitatory neurotransmitter effect, calcium overload, and inflammatory damage.…”