Effect of M-CSF mediated activation of hippocampal microglia on cognitive dysfunction after traumatic brain injury

Objective To investigate the role of macrophage colony-stimulating factor (M-CSF) in cognitive dysfunction after traumatic brain injury (TBI).Methods Adult male SD rats were randomly divided into three groups:a normal control (control) group, a sham operation (sham) group, and a TBI group. A traumatic brain injury model was established according to the Feeney Free fall model. After successful modeling, the animals were allowed to free access to food and movement. Their cognitive function and balance abilities were evaluated by place navigation test and balance beam walking test on days 1, 3, 5 and 7 after TBI. The expression of M-CSF and microglia marker IBA1 in hippocampal CA1 region at each time point after TBI was detected by Western blot. The expression of M-CSF and IBA1 in hippocampal CA1 region on day 3 after TBI was observed by immunofluorescence staining. The morphological changes of microglia on day 3 after TBI were measured by Sholl analysis.Results Compared with the sham group, the TBI group showed remarkably extended escaping latency and increased beam walking test scores on days 1, 3 and 5 after TBI (P<0.05). According to Western blot analysis, the levels of M-CSF and IBA1 in the hippocampal CA1 region significantly increased on day 3 after TBI, compared with those in the sham group. Furthermore, immunofluorescence staining showed that the levels of M-CSF and IBA1 in the hippocampal CA1 region on day 3 after TBI significantly increased, compared with those in the sham group. Sholl analysis indicated significant activation of microglia.Conclusions Cognitive dysfunction and damage of balance ability in rats after TBI are associated with an inflammatory response generated by M-CSF-mediated microglia activation, which peaks on day 3 after TBI.