Ischemia-induced slowly progressive neuronal damage in the rat brain

Ischemic neuronal damage has been believed to make rapid progress in the course of a few days even in delayed selective neuronal death, to say nothing of acute brain necrosis. In the present study, however, we demonstrate for the first time a new type of ischemia-induced neuronal damage which progresses in the course of several weeks or a few months and we tentatively call this process "slowly progressive neuronal damage". We have focused on the chronological changes of neuronal damage in the dorsolateral striatum and neocortex following various durations of transient middle cerebral artery occlusion, which does not cause cerebral infarction and is clinically designated "transient ischemic attack". In the rats subjected to 15 min middle cerebral artery occlusion, the neocortex and lateral striatum were rarely damaged, whereas the small to medium-sized neurons only in the narrow area restricted to the dorsal striatum showed slowly progressive neuronal damage. Prolongation of ischemic duration to 30 min accelerated the evolution of neuronal damage in the dorsolateral striatum and also extended the distribution of neuronal damage to the neocortex, especially to layer III and more superficial layers. Further prolongation of ischemic duration to 45 min resulted in more rapid progress of selective neuronal death in those areas described above, whereas no animal escaped 60 min ischemia, without acute total tissue necrosis in the middle cerebral artery territory. Ischemia-induced slowly progressive neuronal damage may be implicated in the pathogenesis of such slowly progressive neurologic deterioration as dementia or Parkinsonism in patients with cerebral arteriosclerosis.