PMID- 35665627
OWN - NLM
STAT- MEDLINE
DCOM- 20220902
LR  - 20230202
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 247
IP  - 15
DP  - 2022 Aug
TI  - Intermittent hypoxia promotes the recovery of motor function in rats with 
      cerebral ischemia by regulating mitochondrial function.
PG  - 1364-1378
LID - 10.1177/15353702221098962 [doi]
AB  - Hypoxia preconditioning is neuroprotective, but the therapeutic effects of 
      intermittent hypoxia were not fully considered. The present study investigated 
      the neuroprotective effect and mechanism of intermittent hypoxia on motor 
      function after cerebral ischemia and explored alternative clinical treatment 
      options. In total, 36 8-week-old male Sprague-Dawley rats were subjected to 
      60 min of transient middle cerebral artery occlusion (tMCAO) and then randomly 
      divided into a sham-operated group (SHAM), tMCAO-sedentary group (SED), and 
      tMCAO-intermittent hypoxia group (IH). The intervention was performed 1 week 
      after tMCAO and lasted 4 weeks. Rats in the IH group were placed in an animal 
      hypoxic chamber (altitude 5000 m and oxygen concentration of 13%) for 4 h/day and 
      7 days/week, and rats in the SED group were placed in a normoxic environment for 
      4 weeks. Body weights, neurological deficit scores, cerebral infarction volume 
      ratios, gait analyses, mitochondrial structure, adenosine triphosphate (ATP) 
      content and AMO-activated protein kinase (AMPK), peroxisome 
      proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha), and silencing 
      regulatory protein 3 (Sirt3) expression in the peri-ischemic region brain tissues 
      were detected during the intervention. Compared with the SED group, the body 
      weight of the IH group gradually recovered, and the neurological deficit scores 
      were significantly reduced (P < 0.05). The gait analysis results showed that the 
      pressure of the affected paw and the maximum content area, swing speed, stride 
      length, and other parameters were significantly restored (P < 0.05). The cerebral 
      infarction volume ratio was significantly reduced (P < 0.01). Mitochondrial 
      morphological structure damage in the peri-ischemic region brain tissues 
      recovered, the number was significantly increased (P < 0.05), and the expression 
      of AMPK, PGC-1alpha, and Sirt3 proteins (P < 0.05), and ATP content were 
      significantly increased (P < 0.05). Intermittent hypoxia may activate the 
      AMPK-PGC-1alpha-Sirt3 signaling pathway, promote mitochondrial biogenesis, repair 
      mitochondrial ultrastructural damage, and improve mitochondrial function to 
      reduce brain damage and promote motor function recovery in rats with cerebral 
      ischemia.
FAU - Su, Yue
AU  - Su Y
AD  - Department of Physical Medicine and Rehabilitation, Tianjin Medical University 
      General Hospital, Tianjin 300052, China.
FAU - Ke, Changkai
AU  - Ke C
AD  - Department of Physical Medicine and Rehabilitation, Tianjin Medical University 
      General Hospital, Tianjin 300052, China.
FAU - Li, Chen
AU  - Li C
AD  - Department of Physical Medicine and Rehabilitation, Tianjin Medical University 
      General Hospital, Tianjin 300052, China.
FAU - Huang, Chuan
AU  - Huang C
AD  - Department of Physical Medicine and Rehabilitation, Tianjin Medical University 
      General Hospital, Tianjin 300052, China.
FAU - Wan, Chunxiao
AU  - Wan C
AUID- ORCID: 0000-0002-0934-9300
AD  - Department of Physical Medicine and Rehabilitation, Tianjin Medical University 
      General Hospital, Tianjin 300052, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220606
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Transcription Factors)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.5.1.- (Sirtuin 3)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - *Brain Ischemia
MH  - Cerebral Infarction/metabolism
MH  - Hypoxia/metabolism
MH  - Male
MH  - Mitochondria/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Sirtuin 3/metabolism
MH  - Transcription Factors/metabolism
PMC - PMC9442452
OTO - NOTNLM
OT  - Intermittent hypoxia
OT  - cerebral ischemia
OT  - mitochondria
OT  - motor function
COIS- Declaration of Conflicting Interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2022/06/07 06:00
MHDA- 2022/09/03 06:00
PMCR- 2023/02/01
CRDT- 2022/06/06 14:46
PHST- 2022/06/07 06:00 [pubmed]
PHST- 2022/09/03 06:00 [medline]
PHST- 2022/06/06 14:46 [entrez]
PHST- 2023/02/01 00:00 [pmc-release]
AID - 10.1177_15353702221098962 [pii]
AID - 10.1177/15353702221098962 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2022 Aug;247(15):1364-1378. doi: 
      10.1177/15353702221098962. Epub 2022 Jun 6.