Temporal Changes in Cell Marker Expression and Cellular Infiltration in a Controlled Cortical Impact Model in Adult Male C57BL/6 Mice

BACKGROUND: Traumatic injury to the central nervous system (CNS) triggers a robust inflammatory response that leads to axonal damage and secondary degeneration of spared tissue. In contrast, some immune responses have neuroprotective effects. However, detailed information regarding the dynamics of immune responses after traumatic CNS injury is still unavailable. METHODS: In the present study, changes in the immune cells present in the injured brain, spleen, and cervical lymph nodes (CLNs), which are draining lymphatic organs from the CNS, were analyzed after controlled cortical impact (CCI) by flow cytometry and immunohistochemistry. RESULTS: The number of neutrophils and macrophages that infiltrated the injured brain immediately increased 1 d post-injury and declined rapidly thereafter. In the injured brain, resident microglia showed a bimodal increase during the first week and in the chronic phase (≥3 weeks) after injury. Increase in the Iba-1(+) microglia/macrophages was observed around the injured site. Morphologic analysis showed that Iba-1(+) cells were round at 1 week, whereas those at 3 weeks were more ramified. Furthermore, CD86(+)/CD11b(+) M1-like microglia increased at 4 weeks after CCI, whereas CD206(+)/CD11b(+) M2-like microglia increased at 1 week. These results suggest that different subsets of microglia increased in the acute and chronic phases after CCI. Dendritic cells and T cells increased transiently within 1 week in the injured brain. In the CLNs and the spleen, T cells showed dynamic changes after CCI. In particular, the alteration in the number of T cells in the CLNs showed a similar pattern, with a 1-week delay, to that of microglia in the injured brain. CONCLUSION: The data from this study provide useful information on the dynamics of immune cells in CNS injuries.