Maintenance of local cerebral blood flow after acute neuronal death: Possible role of non-neuronal cells

Abstract In brain, a major factor regulating local perfusion is local neuronal activity. However, we have recently discovered that, in rat, five days after selective neuronal destruction in the parietal cortex by local microinjections of the excitotoxin ibotenic acid, local cerebral blood flow, within the lesion, remains in the normal range. We studied whether proliferating non-neuronal cells and/or local changes in microvascular density participate to maintain local cerebral blood flow. Rats were anesthetized (halothane 1–3%), ibotenic acid (10 μg in 1 μ1) was locally microinjected in a restricted region of the parietal cortex, and animals were allowed to recover. Three, five, seven, 11, 30 days later local cerebral blood flow was measured autoradiographically under chloralose anesthesia (40mg/kg, s.c.) by the [ 14 C]iodoantipyrine technique. Cellular density or microvascular area were determined on sections stained with Thionine or processed for the endothelial marker alkaline phosphatase, respectively. Local neurons were destroyed by 24 h after microinjections of ibotenic acid. However, from three to 11 days after lesion local cerebral blood flow was unchanged ( P > 0.05 ; n = 5 ), thereafter declining so that by 30 days blood flow was 48 ± 6% of control ( P ; n = 5) . Cellular density increased within the lesion by 17.5-fold at seven to 11 days (P ) and declined to a 11.7-fold elevation above control at day 30 ( P . New cells consisted of macrophages, endothelium and glial fibrillary acidic protein-positive astrocytes. The microvascular area increased 4.2-fold from three to 11 days ( P . The patency of the presumably newly formed vessels was determined by the presence of intravascular red blood cells, which were revealed histochemically. The area occupied by red blood cells within cerebral microvessels, in contrast to microvascular area, did not increase until seven days after lesion, reaching a 3.2-fold increase at 11 days. Thus within the lesion, local cerebral blood flow remains constant during the phase in which cellular and microvascular density increases. The presumably newly formed vessels cannot contribute to maintain local cerebral blood flow since during this phase they are not patent; rather patency develops coincident with the decline in local cerebral blood flow. We conclude that non-neuronal cells, most likely activated macrophages, may be an important factor regulating local cerebral perfusion, after acute neuronal death.