Effect of basic fibroblast growth factor on hippocampal cholinergic neurons in a rodent model of ischaemic encephalopathy

Basic Clin Pharmacol Toxicol. 2010 Dec;107(6):931-9. doi: 10.1111/j.1742-7843.2010.00603.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism
  • Brain Ischemia / metabolism*
  • Cholinergic Agents / pharmacology*
  • Disease Models, Animal
  • Fibroblast Growth Factor 2 / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Maze Learning / drug effects
  • Memory / drug effects
  • Neurons / drug effects*
  • Neurons / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cholinergic Agents
  • Fibroblast Growth Factor 2