Reactive pericytes in early phase are involved in glial activation and late-onset hypersusceptibility to pilocarpine-induced seizures in traumatic brain injury model mice

Journal of Pharmacological Sciences

Gaku Yamanaka¹  Miho Yasunaga²  Fuyuko Takata³  Kouichi Itoh³  Atsushi Yamauchi³  Kenta Sakai³  Kana Hashiguchi³  Kazuki Tominaga³  Shinya Dohgu³  Yasufumi Kataoka⁴ 

[1] Corresponding author. Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.Fax: [phone].;Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, Tokyo, 160-0023, Japan;Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, 814-0180, Japan;Laboratory for Pharmacotherapy and Experimental Neurology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Kagawa, 769-2193, Japan;

关键词: Traumatic brain injury;    Reactive pericytes;    PDGFRβ;    Imatinib;    Microglia;   

DOI  :  

来源: DOAJ

【 摘 要 】

In this study, among neurovascular unit (NVU) cells, we focused on pericyte reactivity in mice subjected to controlled cortical impact (CCI) to understand how traumatic brain injury (TBI) causes uncoordinated crosstalk in the NVU and alters neuronal activity. Histological analyses of brain pericytes, microglia and astrocytes were performed for up to 28 days after CCI in the injured ipsilateral hippocampus. To evaluate altered neuronal activity caused by CCI, we measured seizure susceptibility to a sub-threshold dose of pilocarpine on postoperative day 7, 14, 21 and 28. Platelet-derived growth factor receptor (PDGFR) β immunoreactivity in pericytes significantly increased from 1 h to 4 days after CCI. The expression of Iba1 and GFAP, as markers of microglia and astrocytes, respectively, increased from 4 to 28 days after CCI. The severity of seizure induced by pilocarpine gradually increased, becoming significant at 28 days after CCI. Then, we treated CCI mice with an inhibitor of PDGFR signaling, imatinib, during the postoperative day 0–4 period. Imatinib lowered seizure susceptibility to pilocarpine and suppressed microglial activation in the injured hippocampus at postoperative day 28. These findings indicate that brain pericytes with rapidly increased PDGFRβ expression may drive TBI-induced dysregulation of NVU function and brain hyperexcitability.

【 授权许可】

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