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Updated: Jan 17, 2026

Controlled Cortical Impact Model for Traumatic Brain Injury
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Controlled Cortical Impact Model for Traumatic Brain Injury

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Activation of AMPK/OPA1 pathway alleviates traumatic brain damage by regulating mitophagy

Hao Wei1, Jiushan Liao2, Wei Gao1

  • 1Fuzhou First General Hospital Affiliated with Fujian Medical University - Department of Neurosurgery - Fujian - China.

Acta Cirurgica Brasileira
|September 24, 2025
PubMed
Abstract

Insights

Activating mitophagy via the AMPK/optic atrophy 1 (OPA1) pathway reduces brain damage and improves neurological function after traumatic brain injury (TBI). This pathway enhances mitophagy, offering a new therapeutic target for TBI recovery.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Mitochondrial Dynamics

Background:

  • Mitophagy is crucial for brain health and is implicated in brain damage.
  • The role of mitophagy in traumatic brain injury (TBI) requires further elucidation.
  • AMP-activated protein kinase (AMPK) influences mitochondrial homeostasis and mitophagy, potentially impacting TBI outcomes.

Purpose of the Study:

  • To investigate the mechanism of the AMPK/optic atrophy 1 (OPA1) pathway in TBI.
  • To explore the role of mitophagy in the context of TBI.
  • To experimentally verify the involvement of the AMPK/OPA1 pathway in TBI-induced brain damage.

Main Methods:

  • A weight-drop TBI mouse model was established.
  • Neurological function, neuronal apoptosis (TUNEL staining), and neuronal morphology (Nissl staining) were assessed.
  • Transmission electron microscopy evaluated mitophagy.
  • Apoptosis-related factors and mitophagy indicators were quantified.

Main Results:

  • Mitophagy activation (MK-8722 or rapamycin) lessened TBI severity and neurological deficits.
  • MK-8722 treatment decreased neuronal apoptosis and enhanced mitophagy.
  • MK-8722 upregulated Parkin, PINK1, and OPA1 while downregulating Bcl-2 and Bax.
  • MK-8722 treatment promoted mitophagy by activating the AMPK/OPA1 pathway.

Conclusions:

  • This study identifies the AMPK/OPA1 pathway as a key player in TBI.
  • The findings highlight mitophagy as a critical mechanism in TBI.
  • This research provides a basis for future therapeutic strategies targeting the AMPK/OPA1 pathway in TBI.

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