Effect of Basic Fibroblast Growth Factor on Hippocampal Cholinergic Neurons in a Rodent Model of Ischaemic Encephalopathy

Abstract

Ischaemic encephalopathy (IE) is a debilitating condition resulting from stroke that can lead to impaired learning and memory related to damage of cholinergic neurons in the hippocampus. The present study used an animal model of IE to test the hypothesis that treatment with basic fibroblast growth factor (bFGF) can reduce cognitive symptoms of IE by increasing the number of cholinergic neurons in the CA region of the hippocampus. The animal model of IE was created surgically by double ligation of the bilateral common carotid arteries. Three groups of Sprague-Dawley rats: sham, IE and IE with bFGF treatment group, were measured for changes in learning and memory using the Morris water maze test. Microscopic and immunohistochemical techniques were used to identify cells that bind bFGF and cholinergic neurons. IE rats treated with bFGF had better scores in the Morris water maze test than the untreated IE group, indicating improved learning and memory in the treated group. Microscopy showed that bFGF crossed the blood-brain barrier, was taken up by neurons in the hippocampus, and that the number of cholinergic neurons in the treated group was significantly increased. These results may provide an experimental basis for the treatment of IE by subcutaneous injection of bFGF.Patients suffering from stroke have been found to have cognitive deficits related to learning and memory [1]. These deficits can cause significant long-term distress and affect quality of life [2]. In a recent study using the rat model to examine the biological basis of these deficits, basic fibroblast growth factor (bFGF) was shown to increase cognitive abilities that had been decreased in a rat model of traumatic brain injury [3]. The current study was designed to further examine the effect of ischaemic encephalopathy (IE) on cognitive abilities in rats and determine the efficacy of basic fibroblast growth factor (bFGF) as a treatment for those suffering from IE-induced cognitive deficits. To examine this, we used both behavioural (Morris water maze) and biological (choline acetyltransferase immunohistochemistry) assays.Previously, both focal [4,5] and global [6] cerebral ischaemia have been shown to cause cognitive deficits in rodent models. In the present experiment, we employed a double common carotid artery ligation method (2-VO) to induce IE. The 2-VO is a permanent occlusion of bilateral internal carotid arteries, which markedly reduces the cerebral blood supply, produces incomplete ischaemia in the anterior part of the brain, and is similar to the pathophysiological processes that occur in chronic cerebrovascular insufficiency. In this model, the blood supply to the supratentorial brain is reduced, whereas blood supply in the brainstem is not affected, thus maintaining the basic functions of the central nervous system. This model is commonly used in research on chronic brain injury [7]. Recent studies have found that 2-VO induces significant learning and memory impairments in rats [8,9] making it a very good model for this study.T...

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