Journal of neurotrauma
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Journal of neurotrauma · Apr 2017
SYNAPTIC MITOCHONDRIA SUSTAIN MORE DAMAGE THAN NON-SYNAPTIC MITOCHONDRIA FOLLOWING TRAUMATIC BRAIN INJURY AND ARE PROTECTED BY CYCLOSPORINE A.
Currently, there are no Food and Drug Administration (FDA)-approved pharmacotherapies for the treatment of those with traumatic brain injury (TBI). As central mediators of the secondary injury cascade, mitochondria are promising therapeutic targets for prevention of cellular death and dysfunction after TBI. One of the most promising and extensively studied mitochondrial targeted TBI therapies is inhibition of the mitochondrial permeability transition pore (mPTP) by the FDA-approved drug, cyclosporine A (CsA). ⋯ This is the first study to examine the effects of CsA on isolated synaptic and non-synaptic mitochondria after experimental TBI. We conclude that synaptic mitochondria sustain more damage than non-synaptic mitochondria 24 h after severe controlled cortical impact injury (CCI), and that intraperitoneal administration of CsA (20 mg/kg) 15 min after injury improves synaptic and non-synaptic respiration, with a significant improvement being seen in the more severely impaired synaptic population. As such, CsA remains a promising neuroprotective candidate for the treatment of those with TBI.
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Journal of neurotrauma · Apr 2017
A novel model of traumatic brain injury in adult zebrafish demonstrates response to injury and treatment comparable with mammalian models.
Traumatic brain injury (TBI) is a leading cause of death and morbidity in industrialized countries with considerable associated health care costs. The cost and time associated with pre-clinical development of TBI therapeutics is lengthy and expensive with a poor track record of successful translation to the clinic. The zebrafish is an emerging model organism in research with unique technical and genomic strengths in the study of disease and development. ⋯ Significant behavioral impairment included decreased swim distance and velocity (p < 0.05), as well as heightened anxiety and altered group social dynamics. Responses to injury were pHIFU dose-dependent and modifiable with MK-801, MDL-28170, or temperature modulation. Together, results indicate that the zebrafish exhibits responses to injury and intervention similar to mammalian TBI pathophysiology and suggest the potential for use to rapidly evaluate therapeutic compounds with high efficiency.
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Journal of neurotrauma · Mar 2017
High-intensity locomotor exercise increases brain-derived neurotrophic factor in individuals with incomplete spinal cord injury.
High-intensity locomotor exercise is suggested to contribute to improved recovery of locomotor function after neurological injury. This may be secondary to exercise-intensity-dependent increases in neurotrophin expression demonstrated previously in control subjects. However, rigorous examination of intensity-dependent changes in neurotrophin levels is lacking in individuals with motor incomplete spinal cord injury (SCI). ⋯ Significant correlations were observed between changes in BDNF and specific indicators of exercise intensity (e.g., rating of perceived exertion; R = 0.43; p = 0.02). Additionally, the data suggest that Val66Met SNP carriers may not exhibit intensity-dependent changes in serum BDNF concentration. Given the known role of BDNF in experience-dependent neuroplasticity, these preliminary results suggest that exercise intensity modulates serum BDNF concentrations and may be an important parameter of physical rehabilitation interventions after neurological injury.
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Journal of neurotrauma · Mar 2017
NorBNI blocks the adverse effects of morphine following spinal cord injury.
Opioids are frequently used for the treatment of pain following spinal cord injury (SCI). Unfortunately, we have shown that morphine administered in the acute phase of SCI results in significant, adverse secondary consequences including compromised locomotor and sensory recovery. Similarly, we showed that selective activation of the κ-opioid receptor (KOR), even at a dose 32-fold lower than morphine, is sufficient to attenuate recovery of locomotor function. ⋯ This suggests that activation of the KOR system plays a significant role in the morphine-induced attenuation of recovery. Our research suggests that morphine, and other opioid analgesics, may be contraindicated for the SCI population. Blocking KOR activity may be a viable strategy for improving the safety of clinical opioid use.