Brain research
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Astrogliosis is a defense response of the CNS to minimize primary damage and to repair injured tissues, but it ultimately generates harmful effects by upregulating inhibitory molecules to suppress neuronal elongation and forming potent barriers to axon regeneration. Chondroitin sulfate proteoglycans (CSPGs) are highly expressed by reactive scars and are potent contributors to the non-permissive environment in mature CNS. Surmounting strong inhibition by CSPG-rich scar is an important therapeutic goal for achieving functional recovery after CNS injuries. ⋯ Thus, CSPGs inhibit axon growth through multiple mechanisms, making them especially potent and difficult therapeutic targets. Identification of CSPG receptors is not only important for understanding the scar-mediated growth suppression, but also for developing novel and selective therapies to promote axon sprouting and/or regeneration after CNS injuries. This article is part of a Special Issue entitled SI: Spinal cord injury.
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Leveraging biomedical informatics for assessing plasticity and repair in primate spinal cord injury.
Recent preclinical advances highlight the therapeutic potential of treatments aimed at boosting regeneration and plasticity of spinal circuitry damaged by spinal cord injury (SCI). With several promising candidates being considered for translation into clinical trials, the SCI community has called for a non-human primate model as a crucial validation step to test efficacy and validity of these therapies prior to human testing. The present paper reviews the previous and ongoing efforts of the California Spinal Cord Consortium (CSCC), a multidisciplinary team of experts from 5 University of California medical and research centers, to develop this crucial translational SCI model. ⋯ By pooling our multidimensional data resources and building a unified database infrastructure for this clinically relevant translational model of SCI, we are now in a unique position to test promising therapeutic strategies' efficacy on the entire syndrome of SCI. We review analyses highlighting the intersection between motor, sensory, autonomic and pathological contributions to the overall restoration of function. This article is part of a Special Issue entitled SI: Spinal cord injury.
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The mechanisms underlying cyclin-dependent kinase 5 (Cdk5)-mediated thermal hyperalgesia induced by inflammation remain poorly understood. In the present study, we examined thermal hyperalgesia provoked by peripheral injection of complete Freund׳s adjuvant (CFA) to test for Cdk5 signaling in the spinal dorsal horns of rats through the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway, which is known to function in mediating inflammatory pain. ⋯ Cdk5, an upstream regulator of p38 and TNF-a, mediates CFA-induced thermal hyperalgesia. As such, pharmacological blocking of the generation of p-p38 mediated by Cdk5 may present a novel approach for diminishing inflammatory pain. This article is part of a Special Issue entitled SI: Spinal cord injury.
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We performed here a systematic review of the studies using transcranial magnetic stimulation (TMS) as a research and clinical tool in patients with spinal cord injury (SCI). Motor evoked potentials (MEPs) elicited by TMS represent a highly accurate diagnostic test that can supplement clinical examination and neuroimaging findings in the assessment of SCI functional level. MEPs allows to monitor the changes in motor function and evaluate the effects of the different therapeutic approaches. ⋯ Some researchers have begun to therapeutically use repetitive TMS (rTMS) in patients with SCI. Initial studies revealed that rTMS can induce acute and short duration beneficial effects especially on spasticity and neuropathic pain, but the evidence is to date still very preliminary and well-designed clinical trials are warranted. This article is part of a Special Issue entitled SI: Spinal cord injury.
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The injured spinal cord does not heal properly. In contrast, tissue repair and functional recovery occur after skin or muscle injuries. The reason for this dichotomy in wound repair is unclear but inflammation, and specifically macrophage activation, likely plays a key role. ⋯ The desynchronized macrophage activation after spinal cord injury is reminiscent of the inflammation present in chronic, non-healing wounds. By refining the role macrophages play in spinal cord injury repair we bring to light important areas for future neuroinflammation and neurotrauma research. This article is part of a Special Issue entitled SI: Spinal cord injury.