Gwak, YS, Kang, J, Unabia, GC and Hulsebosch, CE. Spatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats. Exp Neurol 234: 362-372

ArticleinExperimental Neurology 234(2):362-72 · October 2011with33 Reads
DOI: 10.1016/j.expneurol.2011.10.010 · Source: PubMed
In the spinal cord, neuron and glial cells actively interact and contribute to neurofunction. Surprisingly, both cell types have similar receptors, transporters and ion channels and also produce similar neurotransmitters and cytokines. The neuroanatomical and neurochemical similarities work synergistically to maintain physiological homeostasis in the normal spinal cord. However, in trauma or disease states, spinal glia become activated, dorsal horn neurons become hyperexcitable contributing to sensitized neuronal-glial circuits. The maladaptive spinal circuits directly affect synaptic excitability, including activation of intracellular downstream cascades that result in enhanced evoked and spontaneous activity in dorsal horn neurons with the result that abnormal pain syndromes develop.
    • "Although less relevant than motor recovery, the recovery of sensory functions has a potential impact on locomotion. Furthermore, lesioned animals can develop neuropathic pain [114] which may be attenuated or, worse, aggravated by a treatment. Sensory tests performed after SCI include mechanical and nociceptive tests. "
    [Show abstract] [Hide abstract] ABSTRACT: Human traumatic spinal cord injury (SCI) causes disruption of descending motor and ascending sensory tracts, which leads to severe disturbances in motor functions. To date, no standard therapy for the regeneration of severed spinal cord axons in humans exists. Experimental SCI in rodents is essential for the development of new treatment strat‐ egies and for understanding the underlying mechanisms leading to motor recovery. Here, we provide an overview of the main rodent models and techniques available for the investigation of neuronal regeneration and motor recovery after experimental SCI.
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    • "Within hours, neuronal communication in the remote lumbar region is compromised by inflammatory signaling. The inflammatory signature of the lumbar cord has been associated with the development of neuropathic pain, spasticity, and the impairment of locomotor networks during activity-based training (Detloff et al., 2008; Gwak et al., 2012; Hains and Waxman, 2006; Hansen et al., 2013; Popovich et al., 1996). This study provides the first evidence of how neuroinflammation is initiated specifically in the lumbar but not cervical cord after midthoracic contusion. "
    [Show abstract] [Hide abstract] ABSTRACT: Spinal cord injury (SCI) promotes inflammation along the neuroaxis that jeopardizes plasticity, intrinsic repair and recovery. While inflammation at the injury site is well-established, less is known within remote spinal networks. The presence of bone marrow-derived immune (myeloid) cells in these areas may further impede functional recovery. Previously, high levels of the gelatinase, matrix metalloproteinase-9 (MMP-9) occurred within the lumbar enlargement after thoracic SCI and impeded activity-dependent recovery. Since SCI-induced MMP-9 potentially increases vascular permeability, myeloid cell infiltration may drive inflammatory toxicity in locomotor networks. Therefore, we examined neurovascular reactivity and myeloid cell infiltration in the lumbar cord after thoracic SCI. We show evidence of region-specific recruitment of myeloid cells into the lumbar but not cervical region. Myeloid infiltration occurred with concomitant increases in chemoattractants (CCL2) and cell adhesion molecules (ICAM-1) around lumbar vasculature 24 h and 7 days post injury. Bone marrow GFP chimeric mice established robust infiltration of bone marrow-derived myeloid cells into the lumbar gray matter 24 h after SCI. This cell infiltration occurred when the blood-spinal cord barrier was intact, suggesting active recruitment across the endothelium. Myeloid cells persisted as ramified macrophages at 7 days post injury in parallel with increased inhibitory GAD67 labeling. Importantly, macrophage infiltration required MMP-9.
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    • "Along the process, selected nerve factors would also be released in timely manner to facilitate the whole mechanism. A review by Gwak et al. (2012) had revealed that during SCI, it was profound that astrocytes and microglia activation would take place that corresponds to dorsal horn neuronal hyper-excitability and central neuropathic pain in above-level, at-level and below-level segments remote from the lesion in the spinal cord. This opens a new paradigm that factors secreted by microglia and astrocytes which primarily is GDNF play huge role in the repair mechanism (Dougherty et al., 2000). "
    [Show abstract] [Hide abstract] ABSTRACT: Spinal cord injury (SCI) is a serious and debilitating issue being suffered by wide population worldwide. Extensive treatment approaches have been tested and being verified for their efficacy. Owing to the nature of central nervous system (CNS), the resident stem cells would be triggered in response to any sort of trauma with nerve factors as their communication signals. Apart from physical injuries, damages due to oxidative stress also needs to be addressed while CNS repair mechanism takes place. This study looks at the potential of glial derived nerve factor (GDNF) in addressing the SCI in regards to oxidative damages. A total of 60 Wistar rats were clustered into five groups and GDNF at various concentration were tested in each group. Assessments in terms of oxidative stress parameters were noted and analyzed accordingly. It was noted that GDNF had reduced oxidative damages and increased the levels of anti-oxidants in dose-dependent manner (p<0.05). Though treatment with 10mg/mL and 20mg/mL showed significant changes as compared to control group, these treatment modalities remained insignificant among each other. In conclusion, we demonstrated that GDNF exerted a neuro-protective effect on CNS by inducing anti-oxidants and reducing the levels of oxidative stress in SCI induced rat models.
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