Experimental neurology
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Experimental neurology · Jun 2001
Pro- and anti-inflammatory cytokine gene expression in rat sciatic nerve chronic constriction injury model of neuropathic pain.
Cytokines may be pathophysiologically involved in hyperalgesia. Uncertainty exists about the types of cytokines and their site of action. To study the role of key pro- and anti-inflammatory cytokines in a chronic constriction model of neuropathic pain, mRNA expression of TNF, IL-1beta, IL-6, and IL-10 was quantified using competitive RT-PCR. ⋯ Thermal warming and touch thresholds were significantly reduced at days 3, 7, and 14 in the CCI group, compared with the sham-operated group. Cytokine gene expression in sciatic nerve was significantly increased at day 7 for IL-1beta and IL-6 and at day 14 for TNF. Expression of IL-10 underwent a gradual and progressive increase, reaching statistical significance at day 45.
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Experimental neurology · May 2001
Group I metabotropic glutamate antagonist reduces acute neuronal degeneration and behavioral deficits after traumatic brain injury in rats.
Recent studies indicate that acute activation of Group I mGluRs following traumatic brain injury (TBI) contributes to the ensuing pathophysiology. The present study examined the effects of post-TBI administration of the selective mGluR1 antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) on acute neuronal degeneration in the hippocampus and long-term sensorimotor and learning/memory outcome. In Experiment 1, 26 rats received 0.4, 2.0, or 10.0 nmol AIDA or artificial CSF vehicle infusion into the hippocampus starting 5 min postinjury. ⋯ Acquisition of a Morris water maze (MWM) task was assessed on days 11-15 after TBI. The AIDA-treated group had significantly reduced deficits in beam walk, MWM, and RAM performance compared to the vehicle-treated group. These data indicate that injury-induced acute activation of mGluR1 receptors contributes to both the cellular pathology and the behavioral morbidity associated with TBI.
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Experimental neurology · Apr 2001
Therapeutic effects of environmental enrichment on cognitive function and tissue integrity following severe traumatic brain injury in rats.
Postinjury environmental enrichment (EE) has been shown to alter functional and anatomical outcomes in a number of injury paradigms, including traumatic brain injury (TBI). The question of whether EE alters functional outcome following TBI in a model which produces overt histopathological consequences has not been addressed. We investigated this question using the severe, parasagittal fluid percussion injury (FPI) model. ⋯ At 14 days post-TBI, enriched animals had approximately twofold smaller lesion areas in regions of the cerebral cortex posterior to the injury epicenter (-4.5, -5.8, -6.8 mm relative to bregma; P < 0.05) compared to injured/standard animals. In addition, overall lesion volume for the entire injured cortical hemisphere was significantly smaller in animals recovering in the enriched environment. These results indicate that noninvasive environmental stimulation is beneficial in attenuating cognitive deficits and preserving tissue integrity in a TBI model which causes cerebral contusion and cell death.
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Experimental neurology · Mar 2001
Effects of interleukin-10 (IL-10) on pain behavior and gene expression following excitotoxic spinal cord injury in the rat.
Intraspinal injection of quisqualic acid (QUIS) produces excitotoxic injury with pathophysiological characteristics similar to those associated with ischemic and traumatic spinal cord injury (SCI). Responses to QUIS-induced injury include an inflammatory component, as well as the development of spontaneous and evoked pain behaviors. We hypothesized that QUIS-induced inflammation and subsequent gene expression contribute to the development and progression of pain-related behaviors and that blockade of inflammation-related gene expression leads to the amelioration of these behaviors. ⋯ The results demonstrate that animals receiving systemic injection of IL-10, 30 minutes following QUIS-induced SCI, showed a significant delay in the onset of excessive grooming behavior, a significant reduction in grooming severity, and a significant reduction in the longitudinal extent of a pattern of neuronal loss within the spinal cord characterized as "grooming-type damage." QUIS injections also resulted in an increase in mRNA levels of interleukin-1 beta (IL-1 beta), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), CD95 ligand (CD95-L, also called FAS-L/APO-1L), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Results of QUIS injury plus IL-10 treatment resulted in a significant downregulation of IL1-beta and iNOS mRNA and these results were supported by Western blot analysis of protein levels following IL-10 treatment. These data suggest that IL-10 reduces inflammation and that targeting injury-induced inflammation is an effective strategy for limiting the extent of neuronal damage following excitotoxic SCI and thus the onset and progression of injury-induced pain behaviors.
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Experimental neurology · Feb 2001
Pain behavior and response properties of spinal dorsal horn neurons following experimental diabetic neuropathy in the rat: modulation by nitecapone, a COMT inhibitor with antioxidant properties.
We attempted to characterize a spinal neuronal correlate of painful neuropathy induced by diabetes mellitus (DM). Pain behavior and response properties of spinal dorsal horn neurons were determined in rats with a streptozocin-induced DM. A catechol-O-methyltransferase inhibitor with potent antioxidant properties, nitecapone, was used in an attempt to attenuate neuropathic symptoms. ⋯ The results indicate that increased spontaneous activity in spinal dorsal horn WDR neurons may be causally related to behaviorally observed mechanical hypersensitivity in DM. Attenuation of the increased spontaneous activity in WDR neurons may explain the antihyperalgesic effect by nitecapone, due to naloxone- and alpha-2-adrenoceptor-insensitive mechanisms. DM or nitecapone treatment did not produce significant changes in phasic or tonic descending pain regulation originating in the RVM.