A method for assessing tissue respiration in anatomically defined brain regions
Open accessAbstract
The survival and function of brain cells requires uninterrupted ATP synthesis. Different brain structures subserve distinct neurological functions, and therefore have different energy production/consumption requirements. Typically, mitochondrial function is assessed following their isolation from relatively large amounts of starting tissue, making it difficult to ascertain energy production/failure in small anatomical locations. In order to overcome this limitation, we have developed and optimized a method to measure mitochondrial function in brain tissue biopsy punches excised from anatomically defined brain structures, including white matter tracts. We describe the procedures for maintaining tissue viability prior to performing the biopsy punches, as well as provide guidance for optimizing punch size and the drug doses needed to assess various aspects of mitochondrial respiration. We demonstrate that our method can be used to measure mitochondrial respiration in anatomically defined subfields within the rat hippocampus. Using this method, we present experimental results which show that a mild traumatic brain injury (mTBI, often referred to as concussion) causes differential mitochondrial responses within these hippocampal subfields and the corpus callosum, novel findings that would have been difficult to obtain using traditional mitochondrial isolation methods. Our method is easy to implement and will be of interest to researchers working in the field of brain bioenergetics and brain diseases.
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BSC preserves anatomically brain regions and is highly sensitive to oxygen and glucose changes, allowing recapitulation of pathological changes in energy metabolism.
“Because they preserve their anatomically brain regions, it is also possible to recapitulate pathological changes in energy metabolism because the slices are highly sensitive to oxygen and glucose changes (Underwood et al., 2020).”
From Toxic Concentrations of Glutamate Induce Ferroptosis without Affecting Mitochondrial Respiration in Rodent Brain Slice Cultures (2026) · cites this paper as Underwood et al., 2020
The Results on tissue preparation say brain sections are highly vulnerable to oxygen and glucose deprivation, and the Discussion says tissue punches retain their surrounding cellular milieu and permit measurements in anatomically defined regions. The Results on mild fluid percussion injury also show region-specific changes in mitochondrial respiration. The paper does not show that changing oxygen or glucose in slices recapitulates pathological changes in energy metabolism, so the claimed causal link is unsupported. (LLM, conf=0.83)
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Vaglio-Garro, A., Theuermann, M., Sweis, K. E., Zavadskis, S., Kokas, M., Környei, Z., Karas, M., Tretter, L., Komlódi, T., Weidinger, A., et al. (2026) · eneuro · doi:10.1523/eneuro.0439-25.2026
- Authors
- Underwood, E., Redell, J. B., Zhao, J., Moore, A. N., & Dash, P. K.
- Corresponding author
- Dash, Pramod K.
- Venue
- Scientific Reports
- Published
- 2020-08-06
- Volume
- 10
- Issue
- 1
- Pages
- 13179-13179
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7413397
- OpenAlex
- W3047459414
- Cited by
- 51
- References
- 7
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 13 · 2023: 9 · 2022: 6 · 2021: 6
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5T32GM008792, NS101686-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- mitochondrial respiration, hippocampal subfields, mild traumatic brain injury, concussion, brain bioenergetics, white matter tracts, corpus callosum, tissue viability, ATP production, rat brain
- MeSH terms
- Animals, Brain, Brain Injuries, Cytological Techniques, Hippocampus, Male, Mitochondria, Rats, Sprague-Dawley, Cell Respiration, Rats, White Matter
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