Neonatal microglia and proteinase inhibitors-treated adult microglia improve traumatic brain injury in rats by resolving the neuroinflammation

Microglia participate in the regulation of neuroinflammation caused by traumatic brain injury (TBI). This research aimed to explore the repair effects of intracranial injection of neonatal microglia or protease-treated adult microglia on TBI in rat model. Lateral fluid percussion injury was used to establish rat brain injury model. E64 and serpinA3N were employed for the treatment of adult microglia. Cleaved caspase-3 level was analyzed through immunoblotting assay. Enzyme-linked immunosorbent assay was employed to analyze cytokine and chemokine levels. Astrocytosis and microgliosis were shown by immunofluorescence. The cognitive function of rats was analyzed by water maze. The injection of neonatal microglia inhibited cell apoptosis, reduced astrocytosis and microgliosis, decreased the level of chemokines and cytokines in cortex and ipsilateral hippocampus, and improved cognitive function of TBI rat model. The transplantation of peptidase inhibitors-treated adult microglia also inhibited cell apoptosis, reduced astrocytosis and microgliosis, and improved cognitive function of rats with TBI. The transplantation of either neonatal microglia or peptidase inhibitors-treated adult microglia significantly inhibited the pathogenesis of TBI in rat model, while untreated adult microglia showed no significant effect.