Experimental neurology
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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.
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Experimental neurology · Sep 2013
Environmental enrichment promotes robust functional and histological benefits in female rats after controlled cortical impact injury.
Environmental enrichment (EE) consistently induces marked benefits in male rats after traumatic brain injury (TBI), but whether similar efficacy extends to females is not well established. Hence, the aim of this study was to reassess the effect of EE on functional and histological outcome in female rats after brain trauma. Twenty-four normal cycling adult female rats underwent verification of estrous stage prior to controlled cortical impact (CCI) or sham injury and then were assigned to EE or standard (STD) housing. ⋯ EE also provided significant histological protection as confirmed by increased CA(1/3) cell survival and decreased cortical lesion size vs. STD. These data demonstrate that EE confers robust benefits in female rats after CCI injury, which parallels numerous studies in males and lends further credence for EE as a preclinical model of neurorehabilitation.
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Electrolytic lesion of the medial septum, a basal forebrain nucleus that projects to the hippocampus, prolonged the emergence from general anesthesia in rats. Septal lesioned rats required a longer time to recover from a loss of righting reflex (LORR) and a loss of tail-pinch response after injectable (20 mg/kg i.p. pentobarbital, 5mg/kg i.v. propofol) or volatile (1.5% halothane, 2% isoflurane) anesthetic. When incremental doses of propofol were given i.p., septal lesioned rats as compared to control rats showed LORR at a lower dose of propofol. ⋯ Medial septal lesion resulted in a near complete loss of hippocampal theta rhythm during walking and a general decrease in power of the hippocampal EEG at all frequencies (0-100 Hz), during walking or immobility. It is concluded that lesion of medial septum, in part through a loss of septohippocampal cholinergic afferents, increased the anesthesia response to volatile and injectable general anesthetics, during both induction and emergence. It is suggested that the septohippocampal system participates in many components of general anesthesia including hypnosis, immobility, and analgesia.
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Experimental neurology · Sep 2013
A novel reproducible model of neonatal stroke in mice: comparison with a hypoxia-ischemia model.
Neonatal stroke occurs in 1/4000 live births and leaves life-long neurological impairments, such as cerebral palsy and epilepsy. Currently, the rodent models of neonatal stroke that are available exhibit significant inter-animal variability, which makes it difficult to accurately assess the mechanisms of brain injury and the efficacy of candidate treatments. We aimed to introduce a novel, highly reproducible model of stroke, middle cerebral artery occlusion (MCAO), in immature mice, and to evaluate the reproducibility of this model compared with a conventional hypoxia-ischemia (HI) model. ⋯ Mice with MCAO exhibited significant neurofunctional deficits in the rotarod and open-field tests. Preclinical studies for neonatal stroke could become more reliable using this model, with even a potential reduction in the number of pups required for statistical significance. The contrasting variability between the two models may provide insights into the factors that contribute to inter-animal variability in brain injury.
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Experimental neurology · Sep 2013
Interleukin-10 down-regulates voltage gated sodium channels in rat dorsal root ganglion neurons.
The over-expression of voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons following peripheral nerve injury contributes to neuropathic pain by generation of the ectopic discharges of action potentials. However, mechanisms underlying the change in VGSCs' expression are poorly understood. Our previous work has demonstrated that the pro-inflammatory cytokine TNF-α up-regulates VGSCs. ⋯ Consistent with the electrophysiological results, real-time PCR and western blot revealed that IL-10 (200 pg/ml) down-regulated VGSCs in both mRNA and protein levels and reversed the up-regulation of VGSCs by TNF-α. Moreover, repetitive intrathecal administration of rrIL-10 for 3 days (4 times per day) attenuated mechanical allodynia in L5 spinal nerve ligation model and profoundly inhibited the excitability of DRG neurons. These results suggested that the down-regulation of the sodium channels in DRG neurons might contribute to the therapeutic effect of IL-10 on neuropathic pain.