PMID- 33357774
OWN - NLM
STAT- MEDLINE
DCOM- 20210513
LR  - 20240226
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 145
IP  - 1
DP  - 2021 Jan
TI  - Reactive pericytes in early phase are involved in glial activation and late-onset 
      hypersusceptibility to pilocarpine-induced seizures in traumatic brain injury 
      model mice.
PG  - 155-165
LID - S1347-8613(20)30114-6 [pii]
LID - 10.1016/j.jphs.2020.11.008 [doi]
AB  - 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) beta 
      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 PDGFRbeta expression may drive TBI-induced dysregulation of NVU function 
      and brain hyperexcitability.
CI  - Copyright (c) 2020 The Authors. Production and hosting by Elsevier B.V. All rights 
      reserved.
FAU - Sakai, Kenta
AU  - Sakai K
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, 814-0180, Japan.
FAU - Takata, Fuyuko
AU  - Takata F
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, 814-0180, Japan. Electronic address: 
      ftakata@fukuoka-u.ac.jp.
FAU - Yamanaka, Gaku
AU  - Yamanaka G
AD  - Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, 
      Tokyo, 160-0023, Japan.
FAU - Yasunaga, Miho
AU  - Yasunaga M
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, 814-0180, Japan.
FAU - Hashiguchi, Kana
AU  - Hashiguchi K
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, 814-0180, Japan.
FAU - Tominaga, Kazuki
AU  - Tominaga K
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, 814-0180, Japan.
FAU - Itoh, Kouichi
AU  - Itoh K
AD  - Laboratory for Pharmacotherapy and Experimental Neurology, Kagawa School of 
      Pharmaceutical Sciences, Tokushima Bunri University, Kagawa, 769-2193, Japan.
FAU - Kataoka, Yasufumi
AU  - Kataoka Y
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, 814-0180, Japan.
FAU - Yamauchi, Atsushi
AU  - Yamauchi A
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, 814-0180, Japan.
FAU - Dohgu, Shinya
AU  - Dohgu S
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, 814-0180, Japan.
LA  - eng
PT  - Journal Article
DEP - 20201123
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Brain Injuries, Traumatic/*complications/genetics/metabolism
MH  - Disease Models, Animal
MH  - *Disease Susceptibility
MH  - Gene Expression
MH  - Hippocampus/cytology/injuries/pathology
MH  - Imatinib Mesylate/pharmacology/therapeutic use
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Neuroglia
MH  - Pericytes/*physiology
MH  - Pilocarpine/*adverse effects
MH  - Receptor, Platelet-Derived Growth Factor beta/genetics/metabolism
MH  - Seizures/*etiology/metabolism/prevention & control
MH  - Time Factors
MH  - Mice
OTO - NOTNLM
OT  - Imatinib
OT  - Microglia
OT  - PDGFRbeta
OT  - Reactive pericytes
OT  - Traumatic brain injury
COIS- Declaration of competing interest The authors have no conflicts of interest to 
      declare regarding the conduct or publication of this research.
EDAT- 2020/12/29 06:00
MHDA- 2021/05/14 06:00
CRDT- 2020/12/28 10:25
PHST- 2020/06/26 00:00 [received]
PHST- 2020/10/27 00:00 [revised]
PHST- 2020/11/20 00:00 [accepted]
PHST- 2020/12/28 10:25 [entrez]
PHST- 2020/12/29 06:00 [pubmed]
PHST- 2021/05/14 06:00 [medline]
AID - S1347-8613(20)30114-6 [pii]
AID - 10.1016/j.jphs.2020.11.008 [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2021 Jan;145(1):155-165. doi: 10.1016/j.jphs.2020.11.008. Epub 
      2020 Nov 23.