Increased adult neurogenesis in the subventricular zone in a rat model of sepsis

Abstract

Neurogenesis occurs in the adult brain throughout the lives of all mammals. The dentate gyrus (DG) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricles have been established as the primary sites of adult neurogenesis, and recent studies have shown that inflammation has a modulating effect on adult neurogenesis. However, only limited studies have investigated how neurogenesis is affected during sepsis and sepsis-associated encephalopathy. Therefore, we investigated adult neurogenesis in the cecal ligation and puncture (CLP) model of sepsis using a cell proliferation marker, 5-bromo-2'-deoxyuridine (BrdU). Twenty-four rats were placed into the following three groups: an un-operated control group, a sham-operated group that underwent exactly the same procedures except for CLP, and a CLP group that survived surgical procedures and developed signs of sepsis. Rats were monitored for twenty-four hours before they were euthanized and their brains were harvested. Significantly higher numbers of BrdU-immunoreactive cells were observed in the SVZ of the lateral ventricles in the CLP group as compared with both control groups, while no significant difference was found in the number of DG granule cells between the three groups. The majority of BrdU-positive cells in the SVZ co-expressed the neuronal marker doublecortin but not the astrocytic marker glial fibrillary acidic protein. Taken together, our results suggest that sepsis induced by CLP in rats increases region-specific cellular regeneration, in a possible attempt to compensate for the devastating effect of sepsis and sepsis-associated encephalopathy on the brain.