Differential proliferative response in the postischemic hippocampus, temporal cortex, and olfactory bulb of young adult macaque monkeys

Abstract

We investigated the fate of proliferating cells in the adult monkey brain after global ischemia. We used the thymidine analogue bromodeoxyuridine (BrdU) to label S-phase cells and their progeny in Japanese macaques subjected to global cerebral ischemia for 20 min or to a sham operation. Subsequently, newly generated cells were identified by BrdU immunohistochemistry, and their immunophenotype was determined quantitatively, using specific markers. The ischemic insult significantly increased the number of proliferating cells in the hippocampus and temporal neocortex, where the majority BrdU-labeled cells expressed markers for microglia (Iba1, CD68, and Ham56) or astrocytes (S-100beta and glial fibrillary acidic protein [GFAP]). In contrast, the proliferation level in the parahippocampal region remained unchanged. This discrepancy prompted us to investigate the postischemic response in the olfactory bulb, a well-known site of adult cell generation that is anatomically distant from the above-mentioned regions but that is also subjected to the global ischemic insult. The olfactory bulb contained clusters of proliferating cells expressing markers for neural (Musashi1 and Nestin) and/or neuronal (class III beta-tubulin) progenitors; these were immunophenotypically distinct from other cell types. Their number and distribution were unaltered by ischemia. Our results demonstrate that cell proliferation and differentiation in the adult macaque brain and olfactory bulb are differentially affected by a common insult.