Ellagic acid-induced thrombotic focal cerebral ischemic model in rats

Abstract Introduction Ischemic stroke is a common cause of human disability and death. Animal models of focal cerebral ischemia are widely utilized to mimic human ischemic stroke. Although models of focal cerebral ischemia have been well established, very few evidence is based on triggering the intrinsic coagulation system to induce focal cerebral ischemia. Ellagic acid (EA) has been identified to trigger the intrinsic coagulation system via activating coagulation factor XII. However, it remains unknown whether EA can serve as a novel pharmacological approach to induce a new model of focal cerebral ischemia in rats. Methods EA was used for inducing focal cerebral ischemia in adult rats. The dose- and time-dependent effects of EA were characterized. The cerebral infarction ratio was determined with triphenyltetrazolium chloride staining, and the histopathological analysis of the brain tissue was performed under light microscopy. The neurological deficit score was evaluated by a modified method of Bederson. Malondialdehyde (MDA) level and lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activities in serum were determined by spectrophotometry. Results Injection of EA into the middle cerebral artery of rats was able to generate focal cerebral infarction and increased the neurological deficit score and the brain weight to body weight ratio in dose- and time-dependent manners. Furthermore, EA raised serum LDH activity and MDA level and decreased serum SOD activity in a dose-related fashion. Discussion This is the first evidence to show that EA induces focal cerebral ischemia in rats, which is similar to human ischemia stroke in pathogenesis. This model holds promise for pathological, pharmacological and clinical studies of ischemic stroke.