Global ischemia and behavioural deficits

Global cerebral ischemia in rodents is an established model in experimental research on cerebral ischemia which is characterized morphologically by a selective neuronal damage in the hippocampus, striatum and cortex. Using this model many studies have been performed to examine the pathophysiology of ischemic neuronal damage. Based upon these results it has been analysed whether substances which interact with the pathophysiological processes reduce the ischemic neuronal damage. Besides the morphological changes global ischemia leads to functional changes which can be assessed by behavioural studies. The Morris water maze examines the animals' abilities to learn, remember and go to a place in space only defined by its position relative to distal extramaze cues. In this test ischemic animals display a deficit in spatial learning as revealed by an increase in latency and in swim distance in the escape trials and a deficit in spatial memory as shown by reduced quadrant time and crossings over the former platform position during the probe trial. In several studies it could be demonstrated that neuroprotective strategies which reduce ischemic neuronal damage also attenuate or even completely prevent the ischemia-induced behavioural deficits in the water maze. Transplantation of fetal tissue which can also be used to achieve morphological recovery following global ischemia results in an amelioration of the ischemia-induced deficit. Thus, the water maze can clearly show that transplanted tissue can be functionally relevant. Data from the water maze seem to be a valuable completion to morphology which is especially important with respect to the relevance of experimental studies for clinical trials.