Proliferating cells in the adult primate cerebellar cortex after ischemia

Abstract

INTRODUCTION: Brain ischemia is a devastating neurological condition with significant medical and social impact. Here we investigated the effect of experimental ischemia of different duration on the ability of the adult macaque cerebellum to produce new cells of specific phenotypes. MATERIAL AND METHODS: We used a well-established model of global brain ischemia in young adult Japanese monkeys applying bromodeoxyuridine (BrdU) for 5 days х 100 mg/kg daily. Animals were distributed into different experimental and control groups depending on postischemic survival periods: 4, 9, 15, 23, 44 days (D) and BrdU starting day. Immunohistochemical detection of BrdU+ cells, Iba1+ microglia and GFAP+ astroglia was performed on cryosections. Statistical evaluation of newly generated cells with phenotyping for microglia and astrocytes in various cortical layers of the cerebellum were done. RESULTS and CONCLUSIONS: The numbers of BrdU+ cells in some ischemic groups were significantly higher compared to control animals. By cerebrocerebellum, there was an increasing value by D4 group compared to the control, then slightly reducing in D9 and D15 groups and increasing again by D23 and D44 groups. In the spinocerebellum, an increase was detected only in D44 group. The newly generated cells were dispersed in all cerebellar cortical layers with highest concentration in Purkinje cell layer. Our data show that ischemia stimulates cellular proliferation in the cerebellum but this effect declines with time after ischemia. We found evidence for generation of new microglia but not for astroglia. Our data may contribute to a better understanding of regeneration in the cerebellum after brain ischemia.