Experimental neurology
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Experimental neurology · Jul 2014
Randomized Controlled TrialN-acetylcysteine amide preserves mitochondrial bioenergetics and improves functional recovery following spinal trauma.
Mitochondrial dysfunction is becoming a pivotal target for neuroprotective strategies following contusion spinal cord injury (SCI) and the pharmacological compounds that maintain mitochondrial function confer neuroprotection and improve long-term hindlimb function after injury. In the current study we evaluated the efficacy of cell-permeating thiol, N-acetylcysteine amide (NACA), a precursor of endogenous antioxidant glutathione (GSH), on mitochondrial function acutely, and long-term tissue sparing and hindlimb locomotor recovery following upper lumbar contusion SCI. Some designated injured adult female Sprague-Dawley rats (n=120) received either vehicle or NACA (75, 150, 300 or 600mg/kg) at 15min and 6h post-injury. ⋯ Other designated injured rats (n=21) received continuous NACA (150 or 300mg/kg/day) treatment starting at 15min post-injury for one week to assess long-term functional recovery over 6weeks post-injury. Locomotor testing and novel gait analyses showed significantly improved hindlimb function with NACA that were associated with increased tissue sparing at the injury site. Overall, NACA treatment significantly maintained acute mitochondrial bioenergetics and normalized GSH levels following SCI, and prolonged delivery resulted in significant tissue sparing and improved recovery of hindlimb function.
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Experimental neurology · Jul 2014
Behavioral and anatomical consequences of repetitive mild thoracic spinal cord contusion injury in the rat.
Moderate and severe spinal cord contusion injuries have been extensively studied, yet much less is known about mild injuries. Mild contusions result in transient functional deficits, proceeding to near-complete recovery, but they may render the spinal cord vulnerable to future injuries. However, to date there have been no appropriate models to study the behavioral consequences, anatomical changes, and susceptibility of a mild contusion to repeated injuries, which may occur in children as well as adults during competitive sport activities. ⋯ Repeated injury after 3weeks, when functional recovery has been completed, resulted in worsening of both motor and sensory function, which did not recover to prior levels. Anatomical analyses showed no differences in the volumes of spared white matter, lesion, or cyst, but revealed modest extension of lesion area rostral to the injury epicenter as well as an increase in inflammation and apoptosis. These studies demonstrate that a mild injury model can be used to test efficacy of treatments for repeated injuries and may serve to assist in the formulation of policies and clinical practice regarding mild SCI injury and spinal concussion.
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Experimental neurology · Jul 2014
Functional reorganization of the forepaw cortical representation immediately after thoracic spinal cord hemisection in rats.
Spinal cord injury may produce long-term reorganization of cortical circuits. Little is known, however, about the early neurophysiological changes occurring immediately after injury. On the one hand, complete thoracic spinal cord transection of the spinal cord immediately decreases the level of cortical spontaneous activity and increases the cortical responses to stimuli delivered to the forepaw, above the level of the lesion. ⋯ Importantly, the increased cortical forepaw responses are immediate in the cortex contralateral to the hemisection (significant within 30min after injury), but they are progressive in the cortex ipsilateral to the hemisection (reaching significance only 2.5h after injury). Conversely, the decreased cortical spontaneous activity is progressive both ipsilaterally and contralaterally to the hemisection (again reaching significance only 2.5h after injury). In synthesis, the present work reports a functional reorganization of the forepaw cortical representation immediately after thoracic spinal cord hemisection, which is likely important to fully understand the mechanisms underlying long-term cortical reorganization after incomplete spinal cord injuries.
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Experimental neurology · Jun 2014
Decreased spinal synaptic inputs to phrenic motor neurons elicit localized inactivity-induced phrenic motor facilitation.
Phrenic motor neurons receive rhythmic synaptic inputs throughout life. Since even brief disruption in phrenic neural activity is detrimental to life, on-going neural activity may play a key role in shaping phrenic motor output. To test the hypothesis that spinal mechanisms sense and respond to reduced phrenic activity, anesthetized, ventilated rats received micro-injections of procaine in the C2 ventrolateral funiculus (VLF) to transiently (~30min) block axon conduction in bulbospinal axons from medullary respiratory neurons that innervate one phrenic motor pool; during procaine injections, contralateral phrenic neural activity was maintained. ⋯ Ipsilateral iPMF and csPMF following unilateral withdrawal of phrenic synaptic inputs were associated with proportional increases in phrenic responses to chemoreceptor stimulation (hypercapnia), suggesting iPMF and csPMF increase phrenic dynamic range. These data suggest that local, spinal mechanisms sense and respond to reduced synaptic inputs to phrenic motor neurons. We hypothesize that iPMF and csPMF may represent compensatory mechanisms that assure adequate motor output is maintained in a physiological system in which prolonged inactivity ends life.
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Experimental neurology · Jun 2014
The nucleus raphe magnus OFF-cells are involved in diffuse noxious inhibitory controls.
Diffuse noxious inhibitory controls (DNIC) are very powerful long-lasting descending inhibitory controls which are pivotal in modulating the activity of spinal and trigeminal nociceptive neurons. DNIC are subserved by a loop involving supraspinal structures such as the lateral parabrachial nucleus and the subnucleus reticularis dorsalis. Surprisingly, though, whether the nucleus raphe magnus (NRM), another supraspinal area which is long known to be important in pain modulation, is involved in DNIC is still a matter of discussion. ⋯ Interestingly, selective blockade of ON-cells by microinjecting the broad-spectrum excitatory amino acid antagonist, kynurenate, into the NRM neither affects C-fiber-evoked responses nor attenuates DNIC of trigeminal WDR neurons. These results indicate that the NRM tonically inhibits trigeminal nociceptive inputs and is involved in the neuronal network underlying DNIC. Moreover, within NRM, OFF-cells might be more specifically involved in both the tonic and phasic descending inhibitory controls of trigeminal nociception.