Slow Progression of Neurologic Impairment after Mild Ischemic Insult in Rodents: Relationship to Metabolic and Histologic Changes

Summary

We assessed the relationship between slowly progressing neurologic impairment and metabolic and morphologic changes in two rodent models of mild cerebral ischemia. Mild ischemia was induced by occluding the common carotid artery of Mongolian gerbils twice for 10 min each or by permanently occluding the left internal carotid artery of C57BL6 mice. In the gerbils (n= 13), the stroke index (Ohno, 1984) gradually increased during the first 7 days after the ischemic insult (maturation phenomenon). Their neurologic impairment paralleled the slow progression of ATP depletion in the injured hemisphere. Histologic examination revealed cerebral infarction involving the ipsilateral cortex, caudate nucleus, dorsolateral thalamus, and hippocampus. In the mice (n= 12), blood flow at the left parietotemporal skull (measured by using laser Doppler flowmeter) decreased to 40.2± 16.4% of the pre-ischemic level, and their neurological deficit score gradually increased during 8 days after the induction of ischemia. Tests of foot placement also revealed gradual impairment. Brains frozen at day 2 post-ischemia revealed normal levels of energy metabolism and cerebral protein synthesis in the ipsilatera1 hemisphere, except for two mice with a localized area of mild lactate accumulation at the parietotemporal cortex. TUNEL staining of these two samples revealed scattered neuronal death in this area. Therefore, despite the marked differences between the metabolic and histologic outcomes, the slow neurologic impairment was remarkably similar between the two ischemia models. Our results suggest that various processes in the tissue from animals suffering from ischemia, not its irreversible injury, are important for the slow progression.