4.6 Article

Brain-derived neurotrophic factor and its related enzymes and receptors play important roles after hypoxic-ischemic brain damage

Journal

NEURAL REGENERATION RESEARCH
Volume 16, Issue 8, Pages 1453-+

Publisher

WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1673-5374.303033

Keywords

brain injury; brain-derived neurotrophic factor; enzyme; hypoxia-ischemia; receptors; recovery; repair

Funding

  1. National Natural Science Foundation of China [82001604]
  2. Joint Subject of Southwest Medical University and Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University of China [2018XYLH-004]
  3. National Construction Project of Regional Chinese Medicine Treatment Centre of China [2018205]
  4. National Construction Project of the Second Clinical Research Base of Chinese Medicine of China [2018131]

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The study revealed that the mRNA expression levels of BDNF and its associated enzymes and receptors were upregulated in the ipsilateral hippocampus and cerebral cortex, while downregulated in the contralateral hippocampus and cerebral cortex 6 hours after neonatal hypoxic-ischemic brain damage. These findings suggest that BDNF and its processing enzymes and receptors may play crucial roles in the pathogenesis and recovery processes of neonatal hypoxic-ischemic brain damage.
Brain-derived neurotrophic factor (BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated factors following hypoxia-ischemia induced neonatal brain damage, and the significance of these changes are not fully understood. In the present study, a rat model of hypoxic-ischemic brain damage was established through the occlusion of the right common carotid artery, followed by 2 hours in a hypoxic-ischemic environment. Rats with hypoxic-ischemic brain damage presented deficits in both sensory and motor functions, and obvious pathological changes could be detected in brain tissues. The mRNA expression levels of BDNF and its processing enzymes and receptors (Furin, matrix metallopeptidase 9, tissue-type plasminogen activator, tyrosine Kinase receptor B, plasminogen activator inhibitor-1, and Sortilin) were upregulated in the ipsilateral hippocampus and cerebral cortex 6 hours after injury; however, the expression levels of these mRNAs were found to be downregulated in the contralateral hippocampus and cerebral cortex. These findings suggest that BDNF and its processing enzymes and receptors may play important roles in the pathogenesis and recovery from neonatal hypoxic-ischemic brain damage. This study was approved by the Animal Ethics Committee of the University of South Australia (approval No. U12-18) on July 30, 2018.

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