Journal of neurotrauma
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Journal of neurotrauma · Jun 2019
Spontaneous and stimulus-evoked respiratory rate elevation corresponds to development of allodynia in spinal cord injured rats.
Respiratory complications frequently accompany spinal cord injury (SCI) and slowed breathing has been shown to mitigate pain sensitivity. It is possible that elevated respiratory rates (RRs) signal the emergence of chronic pain after SCI. We previously validated the use of remote electric field sensors to noninvasively track breathing in freely behaving rodents. ⋯ In contusion SCI rats, resting RR increases were less substantial but occurred at all weekly time-points. Increases in brush-evoked RR coincided with full expression of hypersensitivity at 14 (hemisection) or 21 (contusion) days after SCI, and these effects were restricted to the lowest brush speeds. Our results support the possibility that early changes in RR may convey pain information in rats.
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Journal of neurotrauma · Jun 2019
Acteoside improves muscle atrophy and motor function by inducing new myokine secretion in chronic spinal cord injury.
Chronic spinal cord injury (SCI) is difficult to cure, even by several approaches effective at the acute or subacute phase. We focused on skeletal muscle atrophy as a detrimental factor in chronic SCI and explored drugs that protect against muscle atrophy and activate secretion of axonal growth factors from skeletal muscle. We found that acteoside induced the secretion of axonal growth factors from skeletal muscle cells and proliferation of these cells. ⋯ Further, we showed that PKM2 might cross the blood-brain barrier. These results indicate that effects of acteoside on chronic SCI might be mediated by PKM2 secretion from skeletal muscles. This study proposes that the candidate drug acteoside and a new myokine, PKM2, could be used for the treatment of chronic SCI.
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Journal of neurotrauma · Jun 2019
Loureirin B Promotes Axon Regeneration by Inhibiting Endoplasmic Reticulum Stress: Induced Mitochondrial Dysfunction and Regulating the Akt/GSK-3β Pathway after Spinal Cord Injury.
Axon retraction greatly limits functional recovery after spinal cord injury (SCI) and neuron polarization, which affects processes including axon formation and development, is a promising target for promoting axon regeneration. Increasing microtubule stability has been demonstrated to improve intrinsic axon regeneration processes and is critically related to endoplasmic reticulum (ER)-mitochondria interactions. We used real-time polymerase chain reaction, Western blotting, and immunofluorescence to screen a variety of natural compounds, and found that Loureirin B (LrB) effectively promoted neuron polarization and axon regeneration in vitro and in vivo. ⋯ Further, LrB reactivated the Akt/GSK-3β pathway, which plays critical roles in cell survival and microtubule stabilization. Taken together, our results suggest that the effects of LrB on neuron regeneration involve the inhibition of ER stress-induced mitochondrial dysfunction and activation of the Akt/GSK-3β pathway, which further promotes microtubule stabilization. LrB may therefore be a promising candidate for facilitating recovery following SCI.
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Journal of neurotrauma · Jun 2019
Multicenter Study Observational StudyDerivation and initial validation of clinical phenotypes of children presenting with concussion acutely in the Emergency Department: Latent class analysis of a multicentre, prospective cohort, observational study.
The identification of clinical phenotypes may help parse the substantial heterogeneity that characterizes children with concussion. This study used latent class analysis (LCA) to identify discernible phenotypes among children with acute concussion and examine the association between phenotypes and persistent post-concussive symptoms (PPCS) at 4 and 12 weeks post-injury. We conducted LCA of variables representing pre-injury history, clinical presentation, and parent symptom ratings, derived from a prospective cohort, observational study that recruited participants from August 2013 until June 2015 at nine pediatric emergency departments within the Pediatric Emergency Research Canada network. ⋯ Clinical phenotypes based on the profile of group membership across the three LCAs varied significantly in their predicted probability of PPCS at 4 and 12 weeks. The results indicate that children with concussion can be grouped into distinct clinical phenotypes, based on pre-injury history, clinical presentation, and acute symptoms, with markedly different risks of PPCS. With further validation, clinical phenotypes may provide a useful heuristic for clinical assessment and management.
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Journal of neurotrauma · Jun 2019
ReviewHow to Translate Time; the Temporal Aspects of Rodent and Human Pathobiological Processes in Traumatic Brain Injury.
Traumatic brain injury (TBI) triggers multiple pathobiological responses with differing onsets, magnitudes, and durations. Identifying the therapeutic window of individual pathologies is critical for successful pharmacological treatment. Dozens of experimental pharmacotherapies have been successfully tested in rodent models, yet all of them (to date) have failed in clinical trials. ⋯ Limitations toward determining conversion rates for various pathobiological processes include the use of differing outcome measures in experimental and clinical TBI studies and the rarity of longitudinal studies. In order to better translate time and close the translational gap, we suggest 1) using clinically relevant outcome measures, primarily in vivo imaging and blood-based proteomics, in experimental TBI studies and 2) collecting data at multiple post-injury time points with a frequency exceeding the expected information content by two or three times. Combined with a big data approach, we believe these measures will facilitate the translation of promising experimental treatments into clinical use.