頭部外傷後の遅発性けいれん発症における脳ペリサイトの役割

抄録

Traumatic brain injury (TBI) can cause the development of posttraumatic epilepsy (PTE) characterized by delayed onset. Increased convulsion risk persists for a long period, from a few months to several years after TBI. The late-onset PTE is often pharmacoresistant and occurs after an unpredictable latency. Thus, the latent period from TBI to the occurrence of the first unprovoked seizure may offer a window of opportunity for preventing the late-onset PTE. To clarify TBI pathology leading to the late-onset PTE, we observed changes of each cell type constituting neurovascular unit (NVU) in mice subjected to controlled cortical impact (CCI), which is an experimental traumatic brain injury at postoperative day 0-28. CCI mice showed that　increased PDGFRβ expression in pericytes precedes increased Iba1 and GFAP expression in glial cells and neuronal hyperexcitability indicated by pilocarpine-induced convulsive behavior. Treatment with an inhibitor of PDGFRβ in the early phase after CCI suppressed microglial activation and neuronal hyperexcitability at postoperative day 28. Our results indicate that TBI-induced activation of pericytes characterized by increased PDGFRβ expression may drive the development of dysregulated NVU coordination including glial activation and neuronal hyperexcitability after TBI leading to the onset of PTE.