Journal of neurotrauma
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Journal of neurotrauma · Jun 2019
Plasticity induced recovery of breathing occurs at chronic stages after cervical contusion.
Severe midcervical contusion injury causes profound deficits throughout the respiratory motor system that last from acute to chronic time points post-injury. We use chondroitinase ABC (ChABC) to digest chondroitin sulphate proteoglycans within the extracellular matrix (ECM) surrounding the respiratory system at both acute and chronic time points post-injury to explore whether augmentation of plasticity can recover normal motor function. We demonstrate that, regardless of time post-injury or treatment application, the lesion cavity remains consistent, showing little regeneration or neuroprotection within our model. ⋯ To further understand this effect, we assessed the anatomical mechanism of this recovery. Increased EMG activity in previously paralyzed muscles was brought about by activation of spared bulbospinal pathways through the site of injury and/or sprouting of spared serotonergic fibers from the contralateral side of the cord. Accordingly, we demonstrate that alterations to the ECM and augmentation of plasticity at chronic time points post-cervical contusion can cause functional recovery of the respiratory motor system and reveal mechanistic evidence of the pathways that govern this effect.
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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
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
Temporal Neurophysiological Dynamics in Traumatic Brain Injury: Role of Pressure Reactivity and Optimal Cerebral Perfusion Pressure for Predicting Outcome.
Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and the pressure reactivity index (PRx) have been shown to correlate with outcome after traumatic brain injury (TBI), but their temporal evolution is less studied. Optimal CPP (CPPopt; i.e., the CPP with the lowest [optimal] PRx value) has been proposed as a dynamic, individualized CPP target. Our aim was to map the temporal course of these parameters and their relation to outcome, in particular the extent and impact of CPP insults based both on fixed CPP thresholds and on divergence from CPPopt. ⋯ PRx was significant when PRx55-15 was excluded. High PRx55-15 and high grade of monitoring time with CPP > CPPopt, but not the traditional fixed CPP thresholds, were strong predictors for worse clinical outcome. The study supports the concept that CPPopt is an important parameter in TBI management.