Biochemical changes in the rat brain in the chronic stage after transient forebrain ischemia

In recent years, cases of sequelae of cerebrovascular disease such as vascular dementia due to death of many neurons have been increasing. Such neuronal death following brain ischemia had been considerd to be due to an energy deficiency resulting from an impaired respiratory chain. However, the detection of the delayed neuronal death showed that neuronal death is not caused by mere energy deficiency. Most previous studies on delayed neuronal death focused on the changes in morphology and energy metabolism in the acute to subacutte stage. There are few reports concerning biochemical changes in the chronic stage, especially in neurotransmitter receptors. Transient ischemia for 20 minutes in a rat four-vessel occlusion model was induced, and serial histological and biochemical changes were evaluated until the chronic stage. Destruction of pyramidal cells in the CAI area of the hippocampus was completed by 10 days after cerebral ischemia followed by recirculation of cerebral blood flow. Light microscopy showed no progression after this day. The level of acetylcholine (ACh) was significantly decreased in the hippocampus, striatum, and frontal cortex at the termination of ischemia but recovered to normal 21 days after recirculation of cerebral blood flow. The binding sites of muscarinic ACh receptors (mACh-R) per usit of protein were increased in the hippocampus 21 days after recirculation of blood flow. However, no changes were observed in the total number of mACh-R in the entire hippocampus. Thuse finings suggest no changes in the ACh neuronal system in the chronic stage and no direct association between this ayatem and delayed neuronal death. On the other hand, N-methyl-D-aspartate (NMDA) receptors, a subtype of glutamate receptirs, showed no change in the hippocampus until after 10 days, but decreased to half after 21 days despite no evidence of histological progression of neuronal death. Thus, delayed neuronal death after transient forebrain ischemia appears to be deu to release of glutamate, an excitatory amino acid. Our findingd show the specific death of neurons with NMDA receptors for glutamate