Journal of neurotrauma
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Journal of neurotrauma · Nov 2017
Fumaric Acid Esters Attenuate Secondary Degeneration Following Spinal Cord Injury.
Spinal cord injury (SCI) causes permanent changes in motor, sensory, and autonomic functions. Unfortunately, there are no stable cures and current treatments include surgical decompression, methylprednisolone, and hemodynamic control that lead to modest function recovery. Fumaric acid esters (FAEs) were firstly used in the management of an immunological skin disorder, such as psoriasis. ⋯ FAEs significantly reduced the severity of inflammation by a modulation of pro-inflammatory cytokines and apoptosis factors, and increased neutrophic factors such as anti-brain-derived neurotrophic factor (BDNF), anti-glial cell-derived neurotrophic factor (GDNF), and neurotrophin-3 (NT3). Our results showed important protective effects of DMF in an animal model of SCI, considerably improving recovery of motor function, possibly by reducing the secondary inflammation and tissue injury that characterize this model. DMF may constitute a promising target for future SCI therapies.
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Journal of neurotrauma · Nov 2017
Anatomical recruitment of spinal V2a interneurons into phrenic motor circuitry after high cervical spinal cord injury.
More than half of all spinal cord injuries (SCIs) occur at the cervical level, often resulting in impaired respiration. Despite this devastating outcome, there is substantial evidence for endogenous neuroplasticity after cervical SCI. Spinal interneurons are widely recognized as being an essential anatomical component of this plasticity by contributing to novel neuronal pathways that can result in functional improvement. ⋯ Transneuronal tracing with pseudorabies virus (PRV) was used to identify interneurons within the phrenic circuitry. There was a robust increase in the number of PRV-labeled V2a interneurons ipsilateral to the C2 hemisection, demonstrating that significant numbers of these excitatory spinal interneurons were anatomically recruited into the phrenic motor pathway two weeks after injury, a time known to correspond with functional phrenic plasticity. Understanding this anatomical spinal plasticity and the neural substrates associated with functional compensation or recovery post-SCI in a controlled, experimental setting may help shed light onto possible cellular therapeutic candidates that can be targeted to enhance spontaneous recovery.