Global incomplete cerebral ischemia produces predominantly cortical neuronal injury

We determined the neuropathologic damage in a canine model of global incomplete ischemia commonly used in a variety of physiological experiments.

We induced 20 minutes of incomplete ischemia in dogs (n = 9) by increasing intracranial pressure via intraventricular infusion of artificial cerebrospinal fluid to maintain a cerebral perfusion pressure of 10 mm Hg while keeping body temperature at 38 degrees C during and immediately after ischemia. After a 7-day recovery period, animals were perfusion-fixed for neuropathology. In hematoxylin and eosin preparations, ischemic neuronal injury was assessed, neurons were counted, and percentage of cell damage was determined.

No focal neurological deficits or overt seizures were observed during the 7-day recovery period. In superior temporal gyrus, 49 +/- 11% and 70 +/- 10% damage (mean +/- SEM) was observed in layer III pyramidal cells in the crown and sulcus, respectively. All neocortical regions examined showed neuronal damage in layers III and/or V. In hippocampus, 59 +/- 11% damage of pyramidal neurons occurred in CA1, with dorsal (septal) hippocampus showing more injury than ventral (temporal) portions. The caudate nucleus (head) exhibited 27 +/- 7% neuronal injury. In cerebellar cortex (anterior lobule), 70 +/- 7% damage of Purkinje cells occurred, but different folia of cerebellum showed varying degrees of injury. Brain stem and thalamus were minimally affected despite reduced blood flow. Inflammatory changes (leukocytic infiltration and neuronal incrustations) were observed, but only when neuronal degeneration was severe. Pancellular necrosis and infarction did not occur.

This animal model of ischemia causes reproducible neuronal injury primarily in cortical regions without pancellular necrosis and infarction. Damage to subcortical areas is less severe than to cortical areas, despite comparable reductions in regional cerebral blood flow. Therefore, in the presence of regionally uniform but incomplete cerebral ischemia, neocortical and hippocampal pyramidal neurons and cerebellar cortical Purkinje cells are more likely than subcortical neurons to degenerate; alternatively, pyramidal and Purkinje neurons degenerate before neostriatal neurons in this model. This neuronal degeneration may represent an intrinsic cellular mechanism without major contribution of cytotoxic pathways associated with inflammation.