الفهرس 
INTRODUCTION
HippocampusOnly 14 pages are availabe for public view
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Abstract
Limb ischemia reperfusion (I/R) injury is a grave clinical condition associated with serious local and systemic effects causing high morbidity and mortality rates. Although restoration of blood flow to an ischemic organ is essential to prevent irreversible cellular injury, reperfusion per se may augment tissue injury in excess of that produced by ischemia alone. The brain, especially hippocampus, has been reported to be vulnerable to I/R injury. Alpha lipoic acid (ALA) is an endogenous antioxidant with a powerful antioxidative, antinflammatory and antiapoptotic properties.
In this work, we studied the probable restorative effect of ALA on limb I/R-induced structural damage of rat hippocampus by light and electron microscopy. Also, morphometric study and statistical analysis were performed.
Forty adult male albino rats were divided equally into four groups:
• group I: (normal control).
• group II: (I/R-One day). The rats were subjected to bilateral femoral arteries occlusion by clamp technique for 3 hours, followed by reperfusion for one day.
• group III: (I/R-Seven days). The rats were subjected to clamping of bilateral femoral arteries for 3 hours, followed by reperfusion for seven days.
• group IV: (I/R-ALA) Rats were subjected to I/R as group III and daily injected with ALA (100mg/kg, intraperitoneal) for seven days.
At the end of the experiment, the brain was dissected out and processed for general histological staining, immunohistochemical staining for Glial fibrillary acidic protein (GFAP) and ultrastructure examination of the hippocampus.
In I/R groups, many structural changes were observed. The neuronal structural changes included a significant increase in the number of dark neurons with ill defined nuclei and dark staining cytoplasm in addition to dilatation of RER cisternae, mitochondrial alterations and dense bodies’ accumulation. The neuronal degenerative changes were confirmed by morphometric data which revealed a significant reduction in the number of light neurons, in the surface area of neurons and in the thickness of the principal neuronal layers of hippocampus of I/R groups. The degenerative changes observed in the pyramidal neuronal perikarya of I/R groups were reflected on the structure of their dendrites, which showed disorganized microtubules and electron dense mitochondria with disrupted cristae. Astrogliosis; featured by increased number and increased immunoreactivity of astrocytes for GFAP, was observed in all regions of the hippocampus after I/R. The ultrastructure of astrocytes revealed marked swelling of their cell body and processes, damaged mitochondria and markedly elongated or swollen strands of RER. The present study showed some degenerative changes in myelinated nerve fibers, which included splitting and partial loss of myelin sheath with noticeable vacuolation and degeneration of the axoplasm. Most blood capillaries of I/R groups exhibited narrow lumen and irregular basal lamina and their lining endothelium showed electron dense bodies. I/R-induced degenerative changes in the rat hippocampus were more apparent with longer period of reperfusion (group III).
In the present work, ALA noticeably ameliorated the hippocampal neuronal damage following remote limb I/R injury. Light microscopy revealed that most of the principal neurons in the DG, CA3 and CA1 fields had normal appearance. A few dark cells were observed. Electron microscopy of granule and pyramidal neurons revealed great preservation of their normal fine structure. Morphometric analysis revealed a significant increase in the thickness of the granule cell layer in DG and stratum pyramidale layer in CA3 and CA1 fields, in the surface area of granule and pyramidal neurons and in the number of light neurons, in addition to a significant reduction in the number of dark cells. Persistent astrogliosis was present with less degenerative changes of their cell bodies and processes in I/R-ALA treated group compared with I/R non-treated group.Most myelinated nerve fibers and blood capillaries appeared relatively normal.
Conclusion:
• Limb I/R had a deleterious remote effect on the hippocampus, which could explain the cognitive impairment of critical trauma survivors.
• I/R-induced structural changes were time-dependent. More degeneration occurred with longer period of reperfusion. So, the reperfusion-damaging effect was not self limiting, but aggravated by time.
• ALA ameliorated the structural changes in rat hippocampal neuronal tissue following limb I/R injury. Being a natural endogenous antioxidant with wide safety range, the present study encourages the clinical use of ALA in the critical clinical settings with I/R injury.