Journal of neurotrauma
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Journal of neurotrauma · Feb 2021
Acute neural and proteostasis mRNA levels predict chronic locomotor recovery after contusive spinal cord injury.
One of the difficulties in identifying novel therapeutic strategies to manage central nervous system (CNS) trauma is the need for behavioral assays to assess chronic functional recovery. In vitro assays and/or acute behavioral assessments cannot accurately predict long-term functional outcome. Using data from 13 independent T9 moderate contusive spinal cord injury (SCI) studies, we asked whether the ratio of acute (24-72 h post-injury) changes in the levels of neuron-, oligodendrocyte-, astrocyte-specific and/or endoplasmic reticulum stress response (ERSR) messenger ribonucleic acids (mRNAs) could predict the extent of chronic functional recovery. ⋯ This approach can be used to confirm biological action of injected drugs in vivo and to optimize dose and therapeutic window. It may prove useful in cervical and lumbar SCI and in other traumatic CNS injuries such as traumatic brain injury and stroke, where prevention of neuronal loss is paramount to functional recovery. Although the current analysis was directed toward ERSR whose activity was targeted in all but one study, acute mRNA markers for other pathophysiological cascades may be as predictive of chronic recovery when those cascades are targeted for neuroprotection.
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Journal of neurotrauma · Feb 2021
Factors associated with recovery in motor strength, walking ability, and bowel and bladder function after traumatic cauda equina injury.
Traumatic cauda equina injury (TCEI) is usually caused by spine injury at or below L1 and can result in motor and/or sensory impairments and/or neurogenic bowel and bladder. We examined factors associated with recovery in motor strength, walking ability, and bowel and bladder function to aid in prognosis and establishing rehabilitation goals. The analysis cohort was comprised of persons with acute TCEI enrolled in the Rick Hansen Spinal Cord Injury Registry. ⋯ Longer rehabilitation stay and being an older female were associated with improved bladder function. Our results suggest that persons with TCEI have a reasonable chance of recovery in walking ability and bowel and bladder function. This study provides important information for rehabilitation goals setting and communication with patients and their families regarding prognosis.
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Journal of neurotrauma · Feb 2021
Autophagy induction contributes to the neuroprotective impact of intermittent fasting on the acutely injured spinal cord.
Spinal cord injury (SCI) is one of the leading causes of neurological disability and death. So far, there is no satisfactory treatment for SCI, because of its complex and ill-defined pathophysiology. Recently, autophagy has been implicated as protective in acute SCI rat models. ⋯ Treatment with 3-methyladenine (3-MA), a selective inhibitor of autophagy, reversed the downregulated apoptosis-related markers by IF. Finally, IF could activate the adenosine monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway and enhance lysosome function by upregulating transcription factor (TF)EB expression. Altogether, the present findings suggest that IF exerts a neuroprotective effect after acute SCI via the upregulation of autophagy, and further points to dietary interventions as a promising combinatorial treatment for SCI.
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Journal of neurotrauma · Feb 2021
L5 spinal nerve axotomy induces distinct electrophysiological changes in axotomized L5- and adjacent nociceptive L4-dorsal root ganglion neurons in rats in vivo.
Peripheral neuropathic pain (PNP) is a major health problem for which effective drug treatment is lacking. Its underlying neuronal mechanisms are still illusive, but pre-clinical studies using animal models of PNP including the L5-spinal nerve axotomy (L5-SNA) model, suggest that it is partly caused by excitability changes in dorsal root ganglion (DRG) neurons. L5-SNA results in two DRG neuronal groups: (1) axotomized/damaged neurons in L5- plus some in L4-DRGs, and (2) ipsilateral L4-neurons with intact/uninjured fibers intermingling with degenerating L5-fibers. ⋯ We also found several changes in axotomized L5-neurons but not in L4-nociceptive neurons, and some changes in L4-nociceptive but not L5-neurons. The faster AP kinetics (decreased refractory period) in L4-nociceptive neurons that are consistent with their reported hyperexcitability may lead to repetitive firing and thus provide enhanced afferent input necessary for initiating and/or maintaining PNP development. The changes in axotomized L5-neurons may contribute to the central mechanisms of PNP via enhanced neurotransmitter release in the central nervous system (CNS).
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Journal of neurotrauma · Feb 2021
Nanoparticle based estrogen delivery to spinal cord injury site reduces local parenchymal destruction and improves functional recovery.
Spinal cord injury (SCI) patients sustain significant functional impairments; this is causally related to restricted neuronal regeneration after injury. The ensuing reactive gliosis, inflammatory cascade, and glial scar formation impede axonal regrowth. Although systemic anti-inflammatory agents (steroids) have been previously administered to counteract this, no current therapeutic is approved for post-injury neuronal regeneration, in part because of related side effects. ⋯ However, axonal regeneration, vascular endothelial growth factor production, and glial-cell-derived neurotrophic factor levels were increased with estrogen administration. Concomitantly improved locomotor and bladder functional recovery were observed with estrogen administration after injury. Therefore, low-dose site-directed estrogen may provide a future approach for enhanced neuronal repair and functional recovery in SCI patients.