Journal of neurotrauma
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Journal of neurotrauma · Dec 2023
ReviewContrasting experimental rodent aftercare with human clinical treatment for cervical spinal cord injury: Bridging the translational "Valley of Death".
More than half of all spinal cord injuries (SCIs) occur at the cervical level and often lead to life-threatening breathing motor dysfunction. The C2 hemisection (C2Hx) and high cervical contusion mouse and rat models of SCI are widely utilized both to understand the pathological effects of SCI and to develop potential therapies. Despite rigorous research effort, pre-clinical therapeutics studied in those animal models of SCI sometimes fail when evaluated in the clinical setting. ⋯ In this review, we have summarized both the standard clinical interventions used to treat patients with cervical SCI and the various veterinary aftercare protocols used to care for rats and mice after experimentally induced C2Hx and high cervical contusion models of SCI. Through this analysis, we have identified areas of marked dissimilarity between clinical and veterinary protocols and suggest the modification of pre-clinical animal care particularly with respect to analgesia, anticoagulative measures, and stress ulcer prophylaxis. In our discussion, we intend to inspire consideration of potential changes to aftercare for animal subjects of experimental SCI that may help to bridge the translational "Valley of Death" and ultimately contribute more effectively to finding treatments capable of restoring independent breathing function to persons with cervical SCI.
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Journal of neurotrauma · Dec 2023
General anesthesia blocks pain-induced hemorrhage and locomotor deficits after spinal cord injury in rats.
Research has shown that engaging pain (nociceptive) pathways after spinal cord injury (SCI) aggravates secondary injury and undermines locomotor recovery. This is significant because SCI is commonly accompanied by additional tissue damage (polytrauma) that drives nociceptive activity. Cutting communication with the brain by means of a surgical transection, or pharmacologically transecting the cord by slowly infusing a sodium channel blocker (lidocaine) rostral to a thoracic contusion, blocks pain-induced hemorrhage. ⋯ Also examined were the hemodynamic impacts of both pain and anesthetic delivery after SCI. Peripheral pain-input induced an acute increase in systolic blood pressure; isoflurane and pentobarbital prevent this increase, which may contribute to the protective effect of anesthesia. The results suggest that placing patients with SCI in a state akin to a medically induced coma can have a protective effect that blocks the adverse effects of pain.
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Journal of neurotrauma · Dec 2023
Relating spinal injury-induced neuropathic pain and spontaneous afferent activity to sleep and respiratory dysfunction.
Abstract Spinal cord injury (SCI) can induce dysfunction in a multitude of neural circuits including those that lead to impaired sleep, respiratory dysfunction, and neuropathic pain. We used a lower thoracic rodent contusion SCI model of neuropathic pain that has been shown to associate with increased spontaneous activity in primary afferents and hindlimb mechanosensory stimulus hypersensitivity. Here we paired capture of these variables with chronic capture of three state sleep and respiration to more broadly understand SCI-induced physiological dysfunction and to assess possible interrelations. ⋯ Hindlimb mechanosensitivity was assessed weekly, and terminal experiments measured primary afferent spontaneous activity in situ from intact lumbar dorsal root ganglia (DRG). We observed that SCI led to increased spontaneous primary afferent activity (both firing rate and the number of spontaneously active DRGs) that correlated with increased respiratory rate variability and measures of sleep fragmentation. This is the first study to measure and link sleep dysfunction and variability in respiratory rate in a SCI model of neuropathic pain, and thereby provide broader insight into the magnitude of overall stress burden initiated by neural circuit dysfunction after SCI.
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Journal of neurotrauma · Dec 2023
Differences in anatomical outcomes between early chronic and far chronic time points after transplantation of spinal cord neural progenitor cells in mice.
Spinal cord injury (SCI) affects millions of people worldwide. Neural progenitor cell (NPC) transplantation is a promising treatment for regenerating lost spinal cord tissue and restoring neurological function after SCI. We conducted a literature search and found that less than a quarter of experimental rodent cell and tissue transplantation studies have investigated anatomical outcomes at longer than 4 months post-transplantation. ⋯ In contrast, corticospinal axon regeneration into grafts was not diminished over time, but rather increased significantly from early to far chronic periods. Interestingly, we found that graft neuronal density is significantly influenced by sex of the host animal, suggesting that sex-dependent processes may shape graft composition over time. Collectively, these results demonstrate that NPC transplants are dynamic and that commonly assessed outcome measures associated with graft efficacy evolve over the weeks to months post-transplantation into the spinal cord.
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Journal of neurotrauma · Dec 2023
Observational StudyAutonomic Cardiovascular Control, Psychological Wellbeing and Cognitive Performance in People with Spinal Cord Injury.
To examine associations between parameters of psychological well-being, injury characteristics, cardiovascular autonomic nervous system (ANS) control, and cognitive performance in persons with spinal cord injury (SCI) compared with age-matched uninjured controls. This is an observational, cross-sectional study including a total of 94 participants (52 with SCI and 42 uninjured controls: UIC). Cardiovascular ANS responses were continuously monitored at rest and during administration of the Paced Auditory Serial Addition Test (PASAT). ⋯ Self-reported levels of anxiety were significantly related to PASAT score in the SCI group, but there was no significant relationship between PASAT and the other indices of SCI-Quality of Life. Future investigations should more closely examine the relationship among cardiovascular ANS impairments, psychological disorders, and cognitive dysfunction to better elucidate the underpinnings of these deficits and to guide interventions aimed at improving physiological, psychological, and cognitive health after SCI. Tetraplegia, paraplegia, blood pressure variability, cognitive, mood.