2. Academic Validation
  3. Mitochondrial Fusion Promoter Alleviates Brain Damage in Rats with Cardiac Ischemia/Reperfusion Injury

Mitochondrial Fusion Promoter Alleviates Brain Damage in Rats with Cardiac Ischemia/Reperfusion Injury

  • J Alzheimers Dis. 2020;77(3):993-1003. doi: 10.3233/JAD-200495.
Poomarin Surinkaew 1 2 3,  Nattayaporn Apaijai 2 3,  Passakorn Sawaddiruk 2 3 4,  Thidarat Jaiwongkam 2 3,  Sasiwan Kerdphoo 2 3,  Nipon Chattipakorn 2 3 5,  Siriporn C Chattipakorn 2 3 6
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Lamphun Hospital, Lamphun, Thailand.
  • 2 Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
  • 3 Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.
  • 4 Department of Anesthesiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
  • 5 Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
  • 6 Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
PMID: 32804148 DOI: 10.3233/JAD-200495
Abstract

Background: Cardiac ischemia/reperfusion (I/R) injury induces brain damage through increased blood-brain barrier (BBB) breakdown, microglial hyperactivity, pro-inflammatory cytokines, Amyloid-β deposition, loss of dendritic spines, brain mitochondrial dysfunction, and imbalanced mitochondrial dynamics. Previous studies demonstrated that mitochondrial fusion promoter reduced cardiac damage from cardiac I/R injury; however, following cardiac I/R injury, the roles of mitochondrial dynamics on the brain have not been investigated.

Objective: To investigate the effects of pharmacological modulation using mitochondrial fusion promoter (M1) in the brain of rats following cardiac I/R injury.

Methods: Twenty-four male Wistar rats were separated into two groups; 1) sham-operation (n = 8) and 2) cardiac I/R injury (n = 16). Rats in the cardiac I/R injury group were randomly received either normal saline solution as a vehicle or a mitochondrial fusion promoter (M1, 2 mg/kg) intravenously. Both treatments were given to the rats 15 minutes before cardiac I/R injury. At the end of the reperfusion protocol, the brain was rapidly removed to investigate brain mitochondrial function, mitochondrial dynamics proteins, microglial activity, and Alzheimer's disease (AD) related proteins.

Results: Cardiac I/R injury induced brain mitochondrial dynamics imbalance as indicated by reduced mitochondrial fusion proteins expression without alteration in mitochondrial fission, brain mitochondrial dysfunction, BBB breakdown, increased macrophage infiltration, Apoptosis, and AD-related proteins. Pretreatment with M1 effectively increased the expression of mitofusin 2, a mitochondrial outer membrane fusion protein, reduced brain mitochondrial dysfunction, BBB breakdown, macrophage infiltration, Apoptosis, and AD-related proteins in rats following cardiac I/R injury.

Conclusion: This mitochondrial fusion promoter significantly protected rats with cardiac I/R injury against brain damage.

Keywords

Amyloid plaque; brain; heart; ischemia-reperfusion injury; microglia; mitochondrial fusion.

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