| Background and Purpose- Ischemic stroke is a most serious common neurologic disorder resulting from embolic or thrombotic occlusion of the major arteries of the brain, most often the middle cerebral artery. The mechanism of cerebral ischemic injury is complex and involves many pathophysiologic events. Extract of Ginkgo biloba leaves (GBE) contains about 24% flavonoid glycosides, about 6% terpene trilactones (ginkgolides, bilobalide), about 7% proanthocyanidins, and certain low molecular weight organic acids. It's widely used to treat cerebrovascular insufficiency. However, which delivery way of GBE is more efficient remains controversial. In order to provide a more effective mode to prevent and treat ischemic stroke, we employed the model of transient middle cerebral artery occlusion (MCAO) to investigate the effects of pre-treatment (for 7 days before ischemia) and post-treatment (immediately after occlusion of the right middle cerebral artery) with intraperitoneal injection of GBE (100mg/kg) on behaviors and infarct volume, and the number of neurons at the level of cortex and dorsal hippocampus of rats. At the same time, the effects of GBE on focal cerebral ischemia were compared to those of MK-801, a classical high-affinity, selective, noncompetitive NMDA receptor antagonist. Methods- 108 healthy male adult Sprague-Dawley rats were divided into five groups randomly: (I) sham-operated group(n=12);(II) MCAO group(n=24);(III) MK-801 group(n=24); (IV) GBE post-treatment group(n=24);(V) GBE pre-treatment group (n=24). Every group was divided into four subgroups according to the different sacrificed time point: that is 0.5h after MCAO operation, and 1h, 1d, 7d since the restoring of blood flow. Each subgroup of the later four groups was composed of six rats, and the sham-operated group was three. All drugs were administered intraperitoneally. Neurological deficits were evaluated by behavioral tests. Infarct volume was assessed by TTC (2,3,5-triphenyl-tetrazolium chloride) staining. The brain sections in cortex of caudate putamen (CP) and dorsal hippocampus were HE-stained, and functional disturbances of the neurons were detected by immunohistochemical staining of the Neuronal Nuclei (NeuN; a marker of postmitotic neurons) and the microtubule associated protein-2 (MAP-2; a reliable marker for early post-stroke). Results: 1. Behaviors: Neurological deficits of the rats from GBE pre-treatment group had improved significantly compared to MCAO group, while neurological score of GBE post-treatment group was similar to that of MCAO group, MK-801 group showed some serious neurotoxic behaviors. 2. Infarct Analysis: Infarct volume was largest in MCAO group, and had reduced significantly in GBE pre-treatment group and MK-801 group. GBE post-treatment group was similar to MCAO group. 3. Pathomorphology (1) HE staining: Compared to sham-operated group, the number of cells in the cortex of CP of MCAO group was significantly decreased, which was slightly decreased in MK-801 group and GBE pre-treatment group. There was no difference between GBE post-treatment group and MCAO group.(2) NeuN immunohistochemistry staining: Compared with sham-operated group, the number of NeuN immunoreactivity (IR) positive cells in the cortex of CP and CA1, CA3 of the hippocampal formation of MCAO group decreased significantly, and slightly reduced in GBE pre-treatment group and MK-801 group, GBE post-treatment group was similar to MCAO group. (3) MAP2 immunohistochemistry staining: There were few MAP2-IR positive cells in the cortex of CP and CA1, CA3 of the hippocampal formation of MCAO group. There were several MAP2-IR positive cells left in the cortex of CP and CA1, CA3 of the hippocampal formation of Both MK-801 group and GBE pre-treatment group. There was no difference between GBE post-treatment and MCAO group. Conclusion: The effects on rat focal cerebral ischemia were significantly different between GBE post-treatment and GBE pretreatment. Pre-treatment administration of GBE obviously improved the neurological score of MCAO rats,...
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