Experimental neurology
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Experimental neurology · Sep 2013
Functional consequences of ethidium bromide demyelination of the mouse ventral spinal cord.
Ethidium bromide (EB) has been extensively used in the rat as a model of spinal cord demyelination. However, this lesion has not been addressed in the adult mouse, a model with unlimited genetic potential. Here we characterize behavioral function, inflammation, myelin status and axonal viability following bilateral injection of 0.20 mg/mL ethidium bromide or saline into the ventral white matter (VWM) of female C57Bl/6 mice. ⋯ As these data suggest that EB-injection in the mouse spinal cord is a non-remyelinating lesion, we sought to ask whether wheel running could promote recovery by enhancing plasticity of local lumbar circuitry independent of remyelination. This did not occur as BMS and Treadscan assessment revealed no significant effect of wheel running on recovery. However, this study defines the importance of descending ventral motor pathways to locomotor function in the mouse as VWM loss results in a chronic hindlimb deficit.
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Experimental neurology · Sep 2013
Sigma-1 receptor-mediated increase in spinal p38 MAPK phosphorylation leads to the induction of mechanical allodynia in mice and neuropathic rats.
The direct activation of the spinal sigma-1 receptor (Sig-1R) produces mechanical allodynia (MA) and thermal hyperalgesia (TH) in mice. In addition, the blockade of the spinal Sig-1R prevents the induction of MA, but not TH in chronic constriction injury (CCI)-induced neuropathic rats. The present study was designed to investigate whether the increase in spinal p38 MAPK phosphorylation (p-p38 MAPK) mediates Sig-1R-induced MA or TH in mice and the induction of MA in neuropathic rats. ⋯ SB203580 treatment during the maintenance phase (postoperative days 15 to 20) had no effect on CCI-induced MA or TH. These results demonstrate that the increase in spinal p-p38 MAPK is closely associated with the induction of Sig-1R mediated MA, but not TH. Sigma-1 receptor modulation of p-p38 MAPK also plays an important role in the induction, but not the maintenance, of MA in neuropathic pain.
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Experimental neurology · Sep 2013
Diaphragm activation via high frequency spinal cord stimulation in a rodent model of spinal cord injury.
As demonstrated in a canine model, high frequency spinal cord stimulation (HF-SCS) is a novel and more physiologic method of electrical activation of the inspiratory muscles compared to current techniques. The dog model, however, has significant limitations due to cost and societal concerns. Since the rodent respiratory system is also a relevant model for the study of neuronal circuitry function, the aims of the present study were to a) assess the effects of HF-SCS and b) determine the methodology of application of this technique in rats. ⋯ Moreover, HF-SCS was successful in pacing these animals over a 60-min period without evidence of system fatigue. Our results suggest that, similar to the dog model, HF-SCS in the rat results in the activation of spinal cord tracts which synapse with the phrenic motoneuron pool, allowing the processing of the stimulus and consequent physiologic activation of the inspiratory muscles. The rat may be a useful model for further studies evaluating phrenic motoneuron physiology.
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Experimental neurology · Sep 2013
Lesion of the pedunculopontine tegmental nucleus in rat augments cortical activation and disturbs sleep/wake state transitions structure.
The pedunculopontine tegmental nucleus (PPT) represents a major aggregation of cholinergic neurons in the mammalian brainstem, which is important in the generation and maintenance of REM sleep. We investigated the effects of unilateral and bilateral PPT lesions on sleep and all the conventional sleep-state related EEG frequency bands amplitudes, in an attempt to find the EEG markers for the onset and progression of PPT cholinergic neuronal degeneration. The experiments were performed on 35 adult male Wistar rats, chronically implanted for sleep recording. ⋯ The unilateral PPT lesion augmented both Wake theta and REM beta while it also attenuated the relative amplitude of the Wake delta frequency, with a delay of one week. Following a bilateral PPT lesion there was augmentation of the relative amplitude of the Wake, NREM, and REM beta and REM gamma frequency which occurred simultaneously to NREM and Wake delta attenuation. We have shown that the PPT cholinergic neuronal loss sustainably increased the number of the Wake/REM and REM/Wake transitions and augmented sleep-states related cortical activation that was simultaneously expressed by the high frequency amplitude augmentation, as well as Wake and NREM delta frequency attenuation.
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Experimental neurology · Sep 2013
ReviewOpioid administration following spinal cord injury: implications for pain and locomotor recovery.
Approximately one-third of people with a spinal cord injury (SCI) will experience persistent neuropathic pain following injury. This pain negatively affects quality of life and is difficult to treat. Opioids are among the most effective drug treatments, and are commonly prescribed, but experimental evidence suggests that opioid treatment in the acute phase of injury can attenuate recovery of locomotor function. ⋯ A review of the literature, described here, suggests that caution is warranted when administering opioids after SCI. Opioid administration may synergistically contribute to the pathology of SCI to increase the development of pain, decrease locomotor recovery, and leave individuals at risk for infection. Considering these negative implications, it is important that guidelines are established for the use of opioids following spinal cord and other central nervous system injuries.