Mitochondrial neuroprotection in traumatic brain injury: rationale and therapeutic strategies
Shoji Yokobori, Anna T Mazzeo, Shyam Gajavelli
1Department of Neurosurgery, University of Miami Miller School of Medicine, Lois Pope LIFE Center, Room 3-20, 1095 NW 14th Terrace, Miami, FL 33136, USA. RBullock@med.miami.edu.
Abstract:
Traumatic brain injury (TBI) is still the worldwide, leading cause of mortality and morbidity in young adults. The prognosis of TBI patients is strongly affected by secondary brain damage including mitochondrial dysfunctions. In many basic and clinical studies, mitochondrial dysfunctions, including the opening of mitochondrial permeability transition (mPT) pore, and treatments including cyclosporine A (CsA) have been studied. These evidences suggest an important role for mitochondria as therapeutic targets for neuroprotection after TBI. This review summarizes the data about normal and pathological mitochondrial function after TBI, TBI pathobiology relating to mitochondrial dysfunction and therapeutic strategies including drug treatment. This review also mentioned about glucose, lactate, and pyruvate metabolisms in TBI, including the "astrocyte-neuron lactate shuttle (ANLS)" hypothesis. Mitochondrial pathophysiology in TBI is still unclear. Thus, the pharmacological treatment in TBI patient is still challenging. This review could help further understanding of this topic. Hopefully, this could help further development and innovation for drug therapies in TBI.
Insights
Traumatic brain injury (TBI) impairs brain function via mitochondrial damage. This review explores mitochondrial dysfunction in TBI and potential therapeutic targets for neuroprotection.
Area of Science:
- Neuroscience
- Cell Biology
- Pathophysiology
Background:
- Traumatic brain injury (TBI) is a major cause of death and disability globally, particularly in young adults.
- Secondary brain damage, including mitochondrial dysfunction, significantly impacts TBI patient outcomes.
- Mitochondria are implicated in TBI pathobiology, with the mitochondrial permeability transition (mPT) pore and cyclosporine A (CsA) being key areas of study.
Purpose of the Study:
- To review the role of mitochondria in normal and pathological function following TBI.
- To summarize TBI pathobiology concerning mitochondrial dysfunction.
- To explore therapeutic strategies, including drug treatments, for neuroprotection in TBI.
Main Methods:
- Literature review of basic and clinical studies on TBI and mitochondrial function.
- Analysis of data on mitochondrial dysfunction, mPT pore opening, and CsA.
- Examination of glucose, lactate, and pyruvate metabolism, including the astrocyte-neuron lactate shuttle (ANLS) hypothesis.
Main Results:
- Mitochondrial dysfunction is a critical factor in secondary brain damage after TBI.
- Evidence suggests mitochondria are viable therapeutic targets for neuroprotection.
- Metabolic pathways like the ANLS hypothesis are relevant to TBI pathophysiology.
Conclusions:
- Understanding mitochondrial pathophysiology in TBI is crucial but remains incomplete.
- Pharmacological treatment for TBI patients presents significant challenges.
- Further research into mitochondrial targets could drive innovation in TBI drug therapies.
