Journal of neurotrauma
-
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.
-
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.
-
Journal of neurotrauma · Nov 2018
Meta AnalysisEfficacy of Oligodendrocyte Progenitor Cell Transplantation in Rat Models with Traumatic Thoracic Spinal Cord Injury: A Systematic Review and Meta-Analysis.
Spinal cord injury (SCI) is a devastating disease that results in severe motor, sensory, and autonomic dysfunction, for which there are currently no available treatments. Subsequent to the primary mechanical damage, progressive secondary damage further exacerbates the functional deficit. Demyelination may play an important role in the pathogenesis of SCI. ⋯ The percentage of myelinated axons increased significantly in the OPC group compared to that of the control group after OPC transplantation. Area measurements across groups revealed a significant reduction in cavity size in the OPC-treated groups compared to the control group. In conclusion, OPC transplantation provided considerable beneficial effects after traumatic SCI.
-
Journal of neurotrauma · Nov 2018
Clinical TrialTrunk Stability Enabled by Noninvasive Spinal Electrical Stimulation after Spinal Cord Injury.
Electrical neuromodulation of spinal networks improves the control of movement of the paralyzed limbs after spinal cord injury (SCI). However, the potential of noninvasive spinal stimulation to facilitate postural trunk control during sitting in humans with SCI has not been investigated. We hypothesized that transcutaneous electrical stimulation of the lumbosacral enlargement can improve trunk posture. ⋯ During spinal stimulation, the center of pressure (COP) displacements decreased to 1.36 ± 0.98 mm compared with 4.74 ± 5.41 mm without stimulation (p = 0.0156) in quiet sitting, and the limits of stable displacement increased by 46.92 ± 35.66% (p = 0.0156), 36.92 ± 30.48% (p = 0.0156), 54.67 ± 77.99% (p = 0.0234), and 22.70 ± 26.09% (p = 0.0391) in the forward, backward, right, and left directions, respectively. During self-initiated perturbations, the correlation between anteroposterior arm velocity and the COP displacement decreased from r = 0.5821 (p = 0.0007) without to r = 0.5115 (p = 0.0039) with stimulation, indicating improved trunk stability. These data demonstrate that the spinal networks can be modulated transcutaneously with tonic electrical spinal stimulation to physiological states sufficient to generate a more stable, erect sitting posture after chronic paralysis.