PMID- 37353947
OWN - NLM
STAT- MEDLINE
DCOM- 20231120
LR  - 20240418
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 29
IP  - 12
DP  - 2023 Dec
TI  - Cerebral glucagon-like peptide-1 receptor activation alleviates traumatic brain 
      injury by glymphatic system regulation in mice.
PG  - 3876-3888
LID - 10.1111/cns.14308 [doi]
AB  - AIM: We aimed to assess the effects of cerebral glucagon-like peptide-1 receptor 
      (GLP-1R) activation on the glymphatic system and whether this effect was 
      therapeutic for traumatic brain injury (TBI). METHODS: Immunofluorescence was 
      employed to evaluate glymphatic system function. The blood-brain barrier (BBB) 
      permeability, microvascular basement membrane, and tight junction expression were 
      assessed using Evans blue extravasation, immunofluorescence, and western blot. 
      Immunohistochemistry was performed to assess axonal damage. Neuronal apoptosis 
      was evaluated using Nissl staining, terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) staining, and western blot. 
      Cognitive function was assessed using behavioral tests. RESULTS: Cerebral GLP-1R 
      activation restored glymphatic transport following TBI, alleviating BBB 
      disruption and neuronal apoptosis, thereby improving cognitive function following 
      TBI. Glymphatic function suppression by treatment using aquaporin 4 inhibitor 
      TGN-020 abolished the protective effect of the GLP-1R agonist against cognitive 
      impairment. CONCLUSION: Cerebral GLP-1R activation can effectively ameliorate 
      neuropathological changes and cognitive impairment following TBI; the underlying 
      mechanism could involve the repair of the glymphatic system damaged by TBI.
CI  - (c) 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & 
      Sons Ltd.
FAU - Lv, Chuanxiang
AU  - Lv C
AUID- ORCID: 0009-0004-4454-3776
AD  - Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Han, Shuai
AU  - Han S
AD  - Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Sha, Zhuang
AU  - Sha Z
AUID- ORCID: 0000-0002-8110-1481
AD  - Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 
      China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Liu, Mingqi
AU  - Liu M
AD  - Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 
      China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Dong, Shiying
AU  - Dong S
AD  - Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 
      China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Zhang, Chunyun
AU  - Zhang C
AUID- ORCID: 0000-0002-4284-8064
AD  - Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Li, Zean
AU  - Li Z
AD  - Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Zhang, Kang
AU  - Zhang K
AD  - Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Lu, Shouyong
AU  - Lu S
AD  - Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Xu, Zhiyang
AU  - Xu Z
AD  - Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Bie, Li
AU  - Bie L
AD  - Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Jiang, Rongcai
AU  - Jiang R
AD  - Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 
      China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
LA  - eng
GR  - 20230204094YY/Science and Technology Development Plan Project of Jilin Province, 
      China/
GR  - YDZJ202201ZYTS001/Science and Technology Development Plan Project of Jilin 
      Province, China/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230623
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Glp1r protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Apoptosis/physiology
MH  - Blood-Brain Barrier/metabolism
MH  - *Brain Injuries, Traumatic/metabolism
MH  - Disease Models, Animal
MH  - Glucagon-Like Peptide-1 Receptor
MH  - *Glymphatic System/metabolism
PMC - PMC10651945
OTO - NOTNLM
OT  - cognitive impairment
OT  - glucagon-like peptide-1 receptor
OT  - glymphatic system
OT  - traumatic brain injury
COIS- The authors declare that they have no competing interests.
EDAT- 2023/06/24 11:42
MHDA- 2023/11/17 15:28
PMCR- 2023/06/23
CRDT- 2023/06/24 02:03
PHST- 2023/05/21 00:00 [revised]
PHST- 2023/04/02 00:00 [received]
PHST- 2023/05/30 00:00 [accepted]
PHST- 2023/11/17 15:28 [medline]
PHST- 2023/06/24 11:42 [pubmed]
PHST- 2023/06/24 02:03 [entrez]
PHST- 2023/06/23 00:00 [pmc-release]
AID - CNS14308 [pii]
AID - 10.1111/cns.14308 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2023 Dec;29(12):3876-3888. doi: 10.1111/cns.14308. Epub 2023 
      Jun 23.