Journal of neurotrauma
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Journal of neurotrauma · Sep 2018
Sensorimotor Activity Partially Ameliorates Pain and Reduces Nociceptive Fiber Density in the Chronically Injured Spinal Cord.
A large proportion of patients suffering from spinal cord injury (SCI) develop chronic central neuropathic pain. Previously, we and others have shown that sensorimotor training early after SCI can prevent the development of mechanical allodynia. To determine whether training initiated in the subchronic/chronic phase remains effective, correlates of below-level neuropathic pain were analyzed in the hindpaws 5-10 weeks after a moderate T11 contusion SCI (50 kDyn) in adult female C57BL/6 mice. ⋯ This was not due to changes in the number or size distribution of CGRP-labeled lumbar dorsal root ganglion neurons. Treadmill training reduced the CGRP-labeling density in the spinal cord of injured mice, whereas the density of non-peptidergic isolectin-B4 (IB4)+ fibers showed no changes in lamina IIi and a slight reduction of sparse IB4 labeling in laminae III-IV. Thus, sensorimotor activity initiated in the subchronic/chronic phase of SCI remains effective in ameliorating pain behavior and influencing structural changes of the nociceptive system.
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Journal of neurotrauma · Sep 2018
Bcl-2/E1B-19KD-Interacting Protein 3/Light Chain 3 Interaction Induces Mitophagy in Spinal Cord Injury in Rats Both In Vivo and In Vitro.
Autophagy and mitophagy have been shown to occur in spinal cord injury (SCI). Bcl-2/E1B-19KD-interacting protein 3 (BNIP3) and its homologue, NIX, have been implicated in the regulation of mitophagy. The aim of this work was to characterize the mechanisms and role of BNIP3 in SCI-associated mitophagy. ⋯ Downregulation of BNIP3 by RNA interference strengthened the mitochondrial function and decreased cell death in spinal cord neurons under hypoxia. Particularly, BNIP3 knockdown significantly improved neurological recovery and the number of neuronal nuclei-positive cells post-SCI in rats. The present study demonstrated that BNIP3 interacts with LC3 to induce mitophagy, whereas its inhibition provided protective neuronal effects in SCI rat models both in vivo and in vitro.
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Journal of neurotrauma · Sep 2018
Facilitation of Locomotor Spinal Networks Activity by Buspirone after a Complete Spinal Cord Lesion in Mice.
Despite efforts to potentiate spinal cord lesioned (SCL) patients' functional recovery with multi-targeted therapy combining pharmacological treatment and training, consistent improvements in locomotor control by descending transmission or spinal network facilitation are still eluding clinicians and researchers. Lately, United States Food and Drug Administration-approved buspirone has shown promise and promoted locomotor-like movement occurrence in SCL patients, but evidence on how and where it exerts its effects is lacking. The objective of the present study was, first, to verify buspirone effect on locomotor spinal network and to evaluate if it promoted functional recovery when combined with training. ⋯ Buspirone acutely increased the number of steps taken, the coupling strength between hindlimbs, angular excursion of the hip joint during locomotion, and improved paw positioning at contact and paw drag (ps < 0.05). Moreover, it induced long-lasting improvements of paw positioning at contact and paw drag when combined with training in mice after a dual lesion paradigm. Altogether, the results indicate that buspirone exerts considerable acute facilitation of spinally mediated locomotion, and could be used in combination with training to promote functional recovery after SCL.
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Journal of neurotrauma · Sep 2018
Traumatic Injury Leads to Inflammation and Altered Tryptophan Metabolism in the Juvenile Rabbit Brain.
Neuroinflammation after traumatic brain injury (TBI) contributes to widespread cell death and tissue loss. Here, we evaluated sequential inflammatory response in the brain, as well as inflammation-induced changes in brain tryptophan metabolism over time, in a rabbit pediatric TBI model. On post-natal days 5-7 (P5-P7), New Zealand white rabbit littermates were randomized into three groups: naïve (no injury), sham (craniotomy alone), and TBI (controlled cortical impact). ⋯ We found that 1) pro- and anti-inflammatory cytokine levels in the brain injury area were differentially regulated in a time-dependent manner post-injury; 2) indoleamine 2,3 dioxygeenase 1 (IDO1) was upregulated around the injury area in TBI kits that persisted at 21 days post-injury; 3) mean length of serotonin-staining fibers was significantly reduced in the injured brain region in TBI kits for at least 21 days post-injury; and 4) kynurenine level significantly increased at 7 days post-injury. A significant decrease in serotonin/tryptophan ratio and melatonin/tryptophan ratio at 21 days post-injury was noted, suggesting that tryptophan metabolism is altered after TBI. A better understanding of the temporal evolution of immune responses and tryptophan metabolism during injury and repair after TBI is crucial for the development of novel therapeutic strategies targeting these pathways.
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Journal of neurotrauma · Sep 2018
Resting State Electroencephalography and Sports-Related Concussion: A Systematic Review.
Sports-related concussion is associated with a range of short-term functional deficits that are commonly thought to recover within a two-week post-injury period for most, but certainly not all, persons. Resting state electroencephalography (rs-EEG) may prove to be an affordable, accessible, and sensitive method of assessing severity of brain injury and rate of recovery after a concussion. This article presents a systematic review of rs-EEG in sports-related concussion. ⋯ All 16 articles reported some abnormality in rs-EEG activity after a concussion; however, the cortical rhythms that were affected varied. Despite substantial methodological and analytical differences across the 16 studies, the current review suggests that rs-EEG may provide a reliable technique to identify persistent functional changes in athletes after a concussion. Because of the varied approaches, however, considerable work is needed to establish a systematic methodology to assess its efficacy as a marker of return-to-play.