PMID- 37820952
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231106
IS  - 1873-2747 (Electronic)
IS  - 0361-9230 (Linking)
VI  - 203
DP  - 2023 Oct 15
TI  - Arc regulates brain damage and neuroinflammation via Sirt1 signaling following 
      subarachnoid hemorrhage.
PG  - 110780
LID - S0361-9230(23)00205-8 [pii]
LID - 10.1016/j.brainresbull.2023.110780 [doi]
AB  - Aneurysmal subarachnoid hemorrhage (aSAH) accounts for only 5 % of all stroke 
      cases, but carries a heavy burden of morbidity and mortality. Activity regulated 
      cytoskeleton associated protein (Arc) is an immediate early gene (IEG)-coded 
      postsynaptic protein that is involved in synaptic plasticity. Increasing evidence 
      and our previous studies have shown that Arc might be involved in the 
      pathological mechanism of various neurological diseases, such as traumatic brain 
      injury (TBI). In this study, we investigated the level of Arc in cerebrospinal 
      fluids (CSF) of aSAH patients and its potential role in brain damage following 
      experimental SAH model. We found that the levels of Arc in aSAH patients' CSF 
      positively correlated with Hunt-Hess (H&H) grades. Knockdown of endogenous Arc 
      expression by small interfere RNA (siRNA) significantly increased brain edema and 
      oxidative stress following SAH. The results of immunostaining in brain sections 
      showed that knockdown of Arc enhanced activation of microglia and astrocytes. In 
      congruent, generation of inflammatory cytokines following SAH was increased by 
      Si-Arc transfection. The results of western blot analysis showed that knockdown 
      of Arc inhibited the expression of Sirt1 and Nrf2, which was accompanied by 
      decreased enzymatic activities of superoxide dismutase (SOD) and glutathione 
      peroxidase (GSH-px). In addition, activation of sirtuin 1 (Sirt1) via agonist 
      SRT2104 markedly decreased the brain damage and neuroinflammation induced by Arc 
      knockdown. In conclusion, knockdown of endogenous Arc could aggravate brain 
      damage and neuroinflammation following experimental SAH, and Arc levels in aSAH 
      patients' CSF might be a potential indicator of brain damage and prognosis.
CI  - Copyright (c) 2023. Published by Elsevier Inc.
FAU - Chen, Tao
AU  - Chen T
AD  - Department of Neurosurgery, Wuxi Taihu Hospital, Wuxi Clinical College of Anhui 
      Medical University, Wuxi, Jiangsu 214044, China.
FAU - Xu, Ye-Ping
AU  - Xu YP
AD  - Department of Neurosurgery, Wuxi Taihu Hospital, Wuxi Clinical College of Anhui 
      Medical University, Wuxi, Jiangsu 214044, China.
FAU - Chen, Yang
AU  - Chen Y
AD  - Department of Neurology, Wuxi Taihu Hospital, Wuxi Clinical College of Anhui 
      Medical University, Wuxi, Jiangsu 214044, China.
FAU - Sun, Shu
AU  - Sun S
AD  - Department of Pharmacy, Wuxi Taihu Hospital, Wuxi Clinical College of Anhui 
      Medical University, Wuxi, Jiangsu 214044, China.
FAU - Yan, Zhi-Zhong
AU  - Yan ZZ
AD  - Department of Neurosurgery, Wuxi Taihu Hospital, Wuxi Clinical College of Anhui 
      Medical University, Wuxi, Jiangsu 214044, China.
FAU - Wang, Yu-Hai
AU  - Wang YH
AD  - Department of Neurosurgery, Wuxi Taihu Hospital, Wuxi Clinical College of Anhui 
      Medical University, Wuxi, Jiangsu 214044, China. Electronic address: 
      prof_wyh101@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231010
PL  - United States
TA  - Brain Res Bull
JT  - Brain research bulletin
JID - 7605818
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - EC 3.5.1.- (Sirt1 protein, rat)
SB  - IM
MH  - Rats
MH  - Animals
MH  - Humans
MH  - *Subarachnoid Hemorrhage/metabolism
MH  - Sirtuin 1/metabolism
MH  - Rats, Sprague-Dawley
MH  - Neuroinflammatory Diseases
MH  - Brain/metabolism
MH  - *Brain Injuries/metabolism
OTO - NOTNLM
OT  - Arc
OT  - Neuroinflammation
OT  - Sirt1
OT  - Subarachnoid hemorrhage
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/10/12 00:43
MHDA- 2023/10/23 01:18
CRDT- 2023/10/11 19:39
PHST- 2023/02/25 00:00 [received]
PHST- 2023/10/04 00:00 [revised]
PHST- 2023/10/09 00:00 [accepted]
PHST- 2023/10/23 01:18 [medline]
PHST- 2023/10/12 00:43 [pubmed]
PHST- 2023/10/11 19:39 [entrez]
AID - S0361-9230(23)00205-8 [pii]
AID - 10.1016/j.brainresbull.2023.110780 [doi]
PST - ppublish
SO  - Brain Res Bull. 2023 Oct 15;203:110780. doi: 10.1016/j.brainresbull.2023.110780. 
      Epub 2023 Oct 10.