Mongolian gerbil (Meriones Unguiculatus) as a model of cerebral infarction for testing new therapeutic agents

Abstract

Stroke mortality represents the third leading cause of death worldwide, after coronary artery disease and cancer. It has been demonstrated that in Mongolian gerbils, a unilateral hemispheric cerebral infarction can be produced following unilateral occlusion of the carotid artery because of the absence of connecting arteries between the basilar and carotid systems in these animals. The objective of this study was to comprehensively characterize the model of cerebral infarction in gerbil, clinically, biochemically and especially morphologically for prospective use in testing new therapeutic agents. Cerebral infarction was produced by ligation of the left common carotid artery in experimental gerbils. The control animals were sham-operated. One hour after surgery, 0.5 ml of 1% trypan blue was administered intraperitoneally to all animals. Initial clinical evaluations were made 8 h after surgery and every day thereafter for 30 days. On each of days 10 and 30, 4 animals were sacrificed. The degree of cerebral infarction was evaluated on the basis of clinical response, electrolyte and enzyme changes, vascular permeability of blood-brain barrier and morphological alterations. The total post-infarction mortality rate was 50%. The clinical symptoms presented as ipsilateral hemiparesis, ptosis of the eyelid, circling behavior, decreased breathing rate, decreased blood pressure and increased heart rate. Such symptoms developed within 8 h of ligation and persisted to sacrifice at day 30. Creatine kinase increased significantly on the 10th day and remained high to day 30. Increased potassium from the damaged cells and breakdown of the blood-brain barrier were first detected 72 h post-infarction. The morphological data showed evidence of brain cell necrosis, autolysis and phagocytosis 10 and 30 days post-ligation in left hemispheres. Minor intercellular edema and some cell shrinkage was evident in the right brain. Areas of focal necrosis in the vicinity of blood vessels, especially in the left brain suggested a reperfusion injury as a consequence of minimal collateral reflow from the right brain into the left brain microvasculature. Experimental infarction in gerbil recreates the ischemic conditions causing stroke in humans. The animal model may be used for evaluating the efficacy of therapeutic agents that may ameliorate the condition in man.