Publications by authors named "Olivia J Kalimon"
Article Synopsis
- Current research indicates that females generally recover better than males after severe traumatic brain injury (TBI), while the opposite occurs with mild TBI, raising questions about the underlying causes of these sex differences.
- The hormone estrogen may provide protective benefits to mitochondria, which are crucial for energy production and often suffer damage during TBI, and studies have shown that mitochondrial impairment is more pronounced in males.
- The study hypothesized that treating isolated mitochondria with estrogen would enhance their function post-TBI in mice, revealing sex-specific differences in mitochondrial injury 24 hours after severe injury, with males experiencing more extensive bioenergetic and functional deficits compared to females.
Mitochondrial function analysis is a well-established method used in preclinical and clinical investigations to assess pathophysiological changes in various disease states, including traumatic brain injury (TBI). Although there are multiple approaches to assess mitochondrial function, one common method involves respirometric assays utilizing either Clark-type oxygen electrodes or fluorescent-based Seahorse analysis (Agilent). However, these functional analysis methods are typically limited to the availability of freshly isolated tissue samples due to the compromise of the electron transport chain (ETC) upon storage, caused by freeze-thaw-mediated breakdown of mitochondrial membranes.
View Article and Find Full Text PDFArticle Synopsis
- Traumatic brain injury (TBI) affects brain function due to impacts or injuries, with mitochondrial dysfunction being a key issue; while most studies focus on male rodents, this research aimed to explore mitochondrial outcomes in females.
- The study found that females exhibited earlier non-synaptic mitochondrial impairment than males after TBI, while males had earlier issues in the synaptic fraction, indicating subtle sex differences in mitochondrial response times.
- Despite these variations in mitochondrial function, both sexes showed no significant differences in cortical tissue sparing after severe TBI, emphasizing the need to include both genders in future research on mitochondrial function post-injury.
Article Synopsis
- Mild traumatic brain injury (mTBI) leads to issues in brain metabolism due to mitochondrial dysfunction, which presents new potential targets for treatment aimed at restoring cellular balance.
- In a study on rats mimicking military-relevant mTBI, treatment with MP201 (a prodrug of DNP) showed promise in improving mitochondrial respiration in synaptic mitochondria after repeated mild blast injuries.
- Although oxidative damage increased in glia-enriched mitochondria post-injury, MP201 reduced this damage while synaptic mitochondria did not show significant differences in oxidative damage after treatment.
Pioglitazone interacts through the mitochondrial protein mitoNEET to improve brain bioenergetics following traumatic brain injury. To provide broader evidence regarding the therapeutic effects of pioglitazone after traumatic brain injury, the current study is focused on immediate and delayed therapy in a model of mild brain contusion. To assess pioglitazone therapy on mitochondrial bioenergetics in cortex and hippocampus, we use a technique to isolate subpopulations of total, glia-enriched and synaptic mitochondria.
View Article and Find Full Text PDFMonoamine oxidase (MAO) is an enzyme located on the outer mitochondrial membrane that metabolizes amine substrates like serotonin, norepinephrine and dopamine. MAO inhibitors (MAOIs) are frequently utilized to treat disorders such as major depression or Parkinson's disease (PD), though their effects on brain mitochondrial bioenergetics are unclear. These studies measured bioenergetic activity in mitochondria isolated from the mouse cortex in the presence of inhibitors of either MAO-A, MAO-B, or both isoforms.
View Article and Find Full Text PDFTraumatic brain injury (TBI) is a complex disease to study due to the multifactorial injury cascades occurring after the initial blow to the head. One of the most vital players in this secondary injury cascade, and therapeutic target of interest, is the mitochondrion. Mitochondria are important for the generation of cellular energy, regulation of cell death, and modulation of intracellular calcium which leaves these "powerhouses" especially susceptible to damage and dysfunction following traumatic brain injury.
View Article and Find Full Text PDFCyclophilin D (CypD) has been shown to play a critical role in mitochondrial permeability transition pore (mPTP) opening and the subsequent cell death cascade. Studies consistently demonstrate that mitochondrial dysfunction, including mitochondrial calcium overload and mPTP opening, is essential to the pathobiology of cell death after a traumatic brain injury (TBI). CypD inhibitors, such as cyclosporin A (CsA) or NIM811, administered following TBI, are neuroprotective and quell neurological deficits.
View Article and Find Full Text PDF