Journal of neurotrauma
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Journal of neurotrauma · Nov 2018
Increased Levels of Circulating Glial Fibrillary Acidic Protein and Collapsin Response Mediator Protein-2 Autoantibodies in the Acute Stage of Spinal Cord Injury Predict the Subsequent Development of Neuropathic Pain.
Neuropathic pain develops in 40-70% of spinal cord injury (SCI) patients and markedly compromises quality of life. We examined plasma from SCI patients for autoantibodies to glial fibrillary acidic protein (GFAP) and collapsin response mediator protein-2 (CRMP2) and evaluated their relationship to the development of neuropathic pain. In study 1, plasma samples and clinical data from 80 chronic SCI patients (1-41 years post-SCI) were collected and screened for GFAP autoantibodies (GFAPab). ⋯ In study 3, we identified CRMP2 as an autoantibody target (CRMP2ab) in 23% of acute SCI patients. The presence of GFAPab and/or CRMP2ab increased the odds of subsequently developing neuropathic pain within 6 months of injury by 9.5 times (p = 0.006). Our results suggest that if a causal link can be established between these autoantibodies and the development of neuropathic pain, strategies aimed at reducing the circulating levels of these autoantibodies may have therapeutic value.
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Journal of neurotrauma · Nov 2018
Dexmedetomidine Mitigates Microglia-Mediated Neuroinflammation through Upregulation of Programmed Cell Death Protein 1 in a Rat Spinal Cord Injury Model.
Excessive neuroinflammation aggravates neurological damage after spinal cord injury (SCI). Controlling neuroinflammation might favor neuroregeneration and tissue repair. Dexmedetomidine is reported to inhibit post-SCI neuroinflammation in previous research. ⋯ AMPK signaling was responsible for the above-mentioned changes of cytokine expression and M2 microglia polarization. Consistently, intraperitoneal injection of dexmedetomidine hydrochloride had a similar effect on microglia in the rat SCI model. Taken together, our study disclosed a novel mechanism underlying the anti-neuroinflammatory effect of dexmedetomidine: dexmedetomidine promotes AMPK signaling in activated microglia via upregulation of microglial PD-1 expression, and subsequently drives microglia polarization toward M2 type.
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Journal of neurotrauma · Nov 2018
Blood Glutamate Scavenger as a Novel Neuroprotective Treatment in Spinal Cord Injury.
Neurotrauma causes immediate elevation of extracellular glutamate (Glu) levels, which creates excitotoxicity and facilitates inflammation, glial scar formation, and consequently neuronal death. Finding factors that reduce the inflammatory response and glial scar formation, and increase neuronal survival and neurite outgrowth, are of major importance for improving the outcome after spinal cord injury (SCI). In the present study, we evaluated a new treatment aiming to remove central nervous system (CNS) Glu into the systemic blood circulation by intravenous (IV) administration of blood Glu scavengers (BGS) such as the enzyme recombinant glutamate-oxaloacetate transaminase 1 (rGOT1) and its co-substrate. ⋯ These effects were correlated with improved functional recovery of the left paretic hindlimb. Thus, early pharmacological intervention with BGS following SCI may be neuroprotective and create a pro-regenerative environment by modulating glia cell response. In light of our results, the availability of the method to remove excess Glu from CNS without the need to deliver drugs across the blood-brain barrier (BBB) and with minimal or no adverse effects may provide a major therapeutic asset.
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Journal of neurotrauma · Nov 2018
High-Speed Fluoroscopy to Measure Dynamic Spinal Cord Deformation in an In Vivo Rat Model.
Although spinal cord deformation is thought to be a predictor of injury severity, few researchers have investigated dynamic cord deformation, in vivo, during impact. This is needed to establish correlations among impact parameters, internal cord deformation, and histological and functional outcomes. Relying on surface deformations alone may not sufficiently represent spinal cord deformation. ⋯ Residual displacement of the internal beads was significantly greater than that of the surface beads in the cranial-caudal direction but not the dorsoventral direction. Finite element simulation confirmed that the additional bead mass likely had little effect on the internal cord deformations. These results support the merit of this technique for measuring in vivo spinal cord deformation.