Related Experiment Video
Updated: Apr 5, 2026
In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
Published on: October 27, 2020
Inhibition of microRNA-29c protects the brain in a rat model of prolonged hypothermic circulatory arrest
Yongchao Wang1, Tianxiang Gu1, Enyi Shi1
1Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.
Objective:
We sought to investigate the cerebroprotection of a novel microRNA mechanism by targeting peroxisome proliferator-activated receptor gamma coactivator 1-alpha in a rat model of prolonged deep hypothermia circulatory arrest.
Methods:
The right carotid artery and jugular vein of male Sprague-Dawley rats were cannulated for cardiopulmonary bypass. Circulatory arrest was conducted for 60 minutes when the pericranial temperature was cooled to 18°C. The sham group received the surgical procedure without cardiopulmonary bypass and deep hypothermia circulatory arrest; the deep hypothermia circulatory arrest group received cardiopulmonary bypass and deep hypothermia circulatory arrest; lentivirus control vector or lentiviral vector containing antagomiR-29c was given to the deep hypothermia circulatory arrest + vector group or the deep hypothermia circulatory arrest + antagomiR-29c group by intracerebroventricular administration 5 days before cardiopulmonary bypass (n = 8, for each of the 4 groups). Neurologic function was evaluated by the modified hole board test and beam balance task during 14 postoperative days. Expressions of caspase-3, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, and miR-29c in the hippocampus were measured by Western blot and quantitative reverse transcription polymerase chain reaction. Malondialdehyde was measured using the Malondialdehyde Assay Kit (Beyotime, Jiangsu, China).
Results:
Pretreatment with antagomiR-29c significantly decreased the expression of microRNA-29c and increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha in the hippocampus (P < .05 vs deep hypothermia circulatory arrest group). The level of malondialdehyde in the hippocampus was lower in the deep hypothermia circulatory arrest + antagomiR-29c group (P < .05 vs deep hypothermia circulatory arrest group). The neurologic functions were markedly protected in rats pretreated with antagomiR-29c as evidenced by improvement of vestibulomotor and cognitive performance during the early postoperative period. In the deep hypothermia circulatory arrest + antagomiR-29c group, histologic scores of the hippocampus were improved and the level of caspase-3 in the hippocampus was lower (P < .05 vs deep hypothermia circulatory arrest group).
Conclusions:
Inhibition of miR-29c attenuates neurologic injuries induced by prolonged deep hypothermia circulatory arrest through a peroxisome proliferator-activated receptor gamma coactivator 1-alpha pathway.
Insights
Inhibiting microRNA-29c protects the brain from prolonged deep hypothermia circulatory arrest by increasing peroxisome proliferator-activated receptor gamma coactivator 1-alpha, improving neurological function and reducing injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Cardiovascular Research
Background:
- Prolonged deep hypothermia circulatory arrest (DHCA) poses significant risks of neurological injury.
- MicroRNAs (miRNAs) play crucial roles in cellular regulation and have emerged as potential therapeutic targets.
- Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a key regulator of cellular energy metabolism and stress response.
Purpose of the Study:
- To investigate the neuroprotective effects of targeting a novel microRNA mechanism involving miR-29c and PGC-1α in a rat model of DHCA.
- To elucidate the specific pathway through which miR-29c inhibition confers cerebroprotection during prolonged DHCA.
Main Methods:
- Male Sprague-Dawley rats underwent 60 minutes of DHCA at 18°C.
- Intracerebroventricular administration of antagomiR-29c or a control vector was performed 5 days prior to DHCA.
- Neurological function was assessed using behavioral tests, and hippocampal tissue was analyzed for PGC-1α, miR-29c, caspase-3, and malondialdehyde levels.
Main Results:
- Inhibition of miR-29c significantly increased PGC-1α expression in the hippocampus.
- AntagomiR-29c treatment reduced malondialdehyde levels and caspase-3 expression, indicating decreased oxidative stress and apoptosis.
- Rats pretreated with antagomiR-29c demonstrated improved vestibulomotor and cognitive functions post-DHCA, with reduced hippocampal injury.
Conclusions:
- Inhibition of miR-29c provides significant neuroprotection against prolonged DHCA.
- This protective effect is mediated through the PGC-1α pathway.
- Targeting miR-29c represents a promising therapeutic strategy for mitigating neurological damage following DHCA.
