PMID- 36385451
OWN - NLM
STAT- MEDLINE
DCOM- 20240119
LR  - 20240305
IS  - 1868-601X (Electronic)
IS  - 1868-4483 (Linking)
VI  - 15
IP  - 1
DP  - 2024 Feb
TI  - Aerobic Glycolysis Induced by mTOR/HIF-1alpha Promotes Early Brain Injury After 
      Subarachnoid Hemorrhage via Activating M1 Microglia.
PG  - 1-15
LID - 10.1007/s12975-022-01105-5 [doi]
AB  - M1 microglial activation is crucial for the pathogenesis of early brain injury 
      (EBI) following subarachnoid hemorrhage (SAH), and there is growing evidence that 
      glucose metabolism is frequently involved in microglial activation. However, the 
      molecular mechanism of glycolysis and its role in M1 microglial activation in the 
      context of EBI are not yet fully understood. In this study, firstly, the 
      relationship between aerobic glycolysis and M1 microglial activation as well as 
      SAH-induced EBI was researched in vivo. Then, intervention on mammalian target of 
      rapamycin (mTOR) was performed to investigate the effects on glycolysis-dependent 
      M1 microglial activation and EBI and its relationship with hypoxia-inducible 
      factor-1alpha (HIF-1alpha) in vivo. Next, Hif-1alpha was inhibited to analyze its role in 
      aerobic glycolysis, M1 microglial activation, and EBI in vivo. Lastly, both in 
      vivo and in vitro, mTOR inhibition and Hif-1alpha enhancement were administered 
      simultaneously, and the combined effects were further confirmed again. The 
      results showed that aerobic glycolysis and M1 microglial polarization were 
      increased after SAH, and glycolytic inhibition could attenuate M1 microglial 
      activation and EBI. Inhibition of mTOR reduced glycolysis-dependent M1 microglial 
      polarization and EBI severity by down-regulating HIF-1alpha expression, while 
      enhancement had the opposite effects. Blockading HIF-1alpha had the similar effects 
      as suppressing mTOR, while HIF-1alpha agonist worked against mTOR antagonist when 
      administered simultaneously. In conclusion, the present study showed new evidence 
      that aerobic glycolysis induced by mTOR/HIF-1alpha might promote EBI after SAH by 
      activating M1 microglia. This finding provided new insights for the treatment of 
      EBI.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Sun, Xin-Gang
AU  - Sun XG
AD  - Department of Neurology, The Second Hospital Affiliated to Shanxi Medical 
      University, Taiyuan, 030000, Shanxi, China. sunyanxia820701@163.com.
FAU - Chu, Xue-Hong
AU  - Chu XH
AD  - Shanxi Medical University, Taiyuan, 030000, Shanxi, China.
FAU - Godje Godje, Ivan Steve
AU  - Godje Godje IS
AD  - Shanxi Medical University, Taiyuan, 030000, Shanxi, China.
FAU - Liu, Shao-Yu
AU  - Liu SY
AD  - Shanxi Medical University, Taiyuan, 030000, Shanxi, China.
FAU - Hu, Hui-Yu
AU  - Hu HY
AD  - Shanxi Medical University, Taiyuan, 030000, Shanxi, China.
FAU - Zhang, Yi-Bo
AU  - Zhang YB
AD  - Shanxi Medical University, Taiyuan, 030000, Shanxi, China.
FAU - Zhu, Li-Juan
AU  - Zhu LJ
AD  - Shanxi Medical University, Taiyuan, 030000, Shanxi, China.
FAU - Wang, Hai
AU  - Wang H
AD  - Shanxi Medical University, Taiyuan, 030000, Shanxi, China.
FAU - Sui, Chen
AU  - Sui C
AD  - Shanxi Medical University, Taiyuan, 030000, Shanxi, China.
FAU - Huang, Juan
AU  - Huang J
AD  - Shanxi Medical University, Taiyuan, 030000, Shanxi, China.
FAU - Shen, Ying-Jie
AU  - Shen YJ
AD  - Shanxi Medical University, Taiyuan, 030000, Shanxi, China.
LA  - eng
GR  - 201903D321044/Shanxi Province's Great Research Project/
GR  - 2019045/Shanxi Health Committee's Project/
GR  - 20210302123264/Shanxi Province's Basic Research Plan/
PT  - Journal Article
DEP - 20221117
PL  - United States
TA  - Transl Stroke Res
JT  - Translational stroke research
JID - 101517297
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
SB  - IM
MH  - Humans
MH  - Signal Transduction
MH  - Microglia
MH  - *Subarachnoid Hemorrhage/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism/pharmacology
MH  - *Brain Injuries/etiology
MH  - Glycolysis
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/pharmacology
OTO - NOTNLM
OT  - Aerobic glycolysis
OT  - Early brain injury
OT  - Hif-1alpha
OT  - Microglia
OT  - Subarachnoid hemorrhage
OT  - mTOR
EDAT- 2022/11/18 06:00
MHDA- 2024/01/19 06:42
CRDT- 2022/11/17 11:04
PHST- 2022/04/15 00:00 [received]
PHST- 2022/11/12 00:00 [accepted]
PHST- 2022/10/19 00:00 [revised]
PHST- 2024/01/19 06:42 [medline]
PHST- 2022/11/18 06:00 [pubmed]
PHST- 2022/11/17 11:04 [entrez]
AID - 10.1007/s12975-022-01105-5 [pii]
AID - 10.1007/s12975-022-01105-5 [doi]
PST - ppublish
SO  - Transl Stroke Res. 2024 Feb;15(1):1-15. doi: 10.1007/s12975-022-01105-5. Epub 
      2022 Nov 17.