ABSTRACT

Ischemic stroke is a major public health issue that requires urgent efforts toward development of novel remedies, and focal brain ischemia animal models signifi cantly aid in these efforts. They have been developed with signifi cant effort to closely mimic the changes that occur during and after human stroke. Models help us to learn about the pathogenesis of stroke and to defi ne the biochemical changes in tissue during ischemia, toward potential discovery of mechanisms involved in the evolution of ischemic injury. These discoveries could lead to the development of novel molecules designed to reduce the undesirable consequences of ischemia, and these same animal models can be utilized to test whether the novel molecules have benefi cial anti-ischemic effects in vivo. When combined with various imaging techniques, such as MRI or positron emission tomography, these models provide versatile information on the evolution of ischemic damage, pathophysiologic aspects, and the size of the lesion. In that human ischemic stroke is often caused by occlusion of the middle cerebral artery (MCA) or one of its branches ( 1 ), most focal cerebral ischemia models were developed to induce ischemia within the MCA territory. Ideally, an ischemic stroke animal model satisfi es the following criteria ( 2 ): ( i ) the ischemic processes and pathophysiologic changes should be relevant to human ischemic stroke, ( ii ) the ischemic lesion should be reproducible, ( iii ) the technique used to induce ischemia should be relatively easy to perform and minimally invasive, ( iv ) physiologic variables can be monitored and maintained within normal ranges, ( v ) brain samples should be readily available for outcome measurements, such as histopathologic, biochemical, and molecular biologic evaluation and ( vi ) the cost and effort should be reasonable.