Experimental neurology
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Experimental neurology · Dec 2007
Long-term synaptic plasticity in the spinal dorsal horn and its modulation by electroacupuncture in rats with neuropathic pain.
Our previous study has reported that electroacupuncture (EA) at low frequency of 2 Hz had greater and more prolonged analgesic effects on mechanical allodynia and thermal hyperalgesia than that EA at high frequency of 100 Hz in rats with neuropathic pain. However, how EA at different frequencies produces distinct analgesic effects on neuropathic pain is unclear. Neuronal plastic changes in spinal cord might contribute to the development and maintenance of neuropathic pain. ⋯ Results from our present study suggest that (1) hyperexcitability in the spinal nociceptive synaptic transmission may occur after nerve injury, which may contribute to the development of neuropathic pain; (2) EA at low or high frequency has a different effect on modulating spinal synaptic plasticities in rats with neuropathic pain. The different modulation on spinal LTD or LTP by low- or high-frequency EA may be a potential mechanism of different analgesic effects of EA on neuropathic pain. LTD of synaptic strength in the spinal dorsal horn in SNL rats may contribute to the long-lasting analgesic effects of EA at 2 Hz.
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Experimental neurology · Nov 2007
Modulation of the cAMP signaling pathway after traumatic brain injury.
Traumatic brain injury (TBI) results in both focal and diffuse brain pathologies that are exacerbated by the inflammatory response and progress from hours to days after the initial injury. Using a clinically relevant model of TBI, the parasagittal fluid-percussion brain injury (FPI) model, we found injury-induced impairments in the cyclic AMP (cAMP) signaling pathway. Levels of cAMP were depressed in the ipsilateral parietal cortex and hippocampus, as well as activation of its downstream target, protein kinase A, from 15 min to 48 h after moderate FPI. ⋯ Traumatic axonal injury, characterized by beta-amyloid precursor protein deposits in the external capsule, was also significantly reduced in rolipram-treated animals. Furthermore, levels of the pro-inflammatory cytokines, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), were significantly decreased with rolipram treatment. These results demonstrate that the cAMP-PKA signaling cascade is downregulated after TBI, and that treatment with a PDE IV inhibitor improves histopathological outcome and decreases inflammation after TBI.
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Experimental neurology · Nov 2007
Chronic inhalation of rotenone or paraquat does not induce Parkinson's disease symptoms in mice or rats.
Epidemiological studies suggest that some pesticides might constitute a risk factor for Parkinson's disease (PD). However, risk assessment cannot be performed in the current experimental animal models because they use non-natural pathways of pesticide exposure, such as intraperitoneal or intravenous injection, that might bypass body defences. A new model based on daily inoculation of neurotoxins in the nasal cavity of C57BL/6 mice for 30 days was used to evaluate risk of three complex I inhibitors, 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP), rotenone and paraquat. ⋯ By contrast, rotenone-treated mice or rats were asymptomatic. Paraquat induced severe hypokinesia and vestibular damage but did not alter the nigrostriatal system. The new animal model described here, based on chronic intranasal inoculation of neurotoxicants, provides a new tool to assess the potential danger of environmental toxins as risk factors for development of PD.
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Experimental neurology · Oct 2007
rAAV-mediated nigral human parkin over-expression partially ameliorates motor deficits via enhanced dopamine neurotransmission in a rat model of Parkinson's disease.
We hypothesized that over-expressing the E3 ligase, parkin, whose functional loss leads to Parkinson's disease, in the nigrostriatal tract might be protective in the unilateral 6-hydroxydopamine (6-OHDA) rat lesion model. Recombinant adeno-associated virus (rAAV) encoding human parkin or green fluorescent protein (GFP) was injected into the rat substantia nigra 6 weeks prior to a four-site striatal 6-OHDA lesion. Vector-mediated parkin over-expression significantly ameliorated motor deficits as measured by amphetamine-induced rotational behavior and spontaneous behavior in the cylinder test but forelimb akinesia as assessed by the stepping test was unaffected. rAAV-mediated human parkin was expressed in the nigrostriatal tract, the substantia pars reticulata, and the subthalamic nucleus. ⋯ When challenged with amphetamine, parkin treated rats tended to display asymmetries biased away from the treated hemisphere. Nigral parkin over-expression induced increases in both striatal TH and DA levels. Therefore, while parkin over-expression exerted no protective effect on the nigrostriatal DA system, parkin appeared to enhance the efficiency of nigrostriatal DA transmission in intact nigral DA neurons likely due to the observed increases in TH.
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Experimental neurology · Sep 2007
Impaired antibody synthesis after spinal cord injury is level dependent and is due to sympathetic nervous system dysregulation.
Individuals with spinal cord injury (SCI) are highly susceptible to infection. This post-traumatic immune suppression is thought to occur via alterations in sympathetic nervous system (SNS) or hypothalamic-pituitary-adrenal (HPA) axis function. Normally, the HPA axis and SNS help coordinate proper immune function. ⋯ The immunosuppressive effects of T3 SCI were caused by NE acting at beta2-adrenergic receptors (beta2AR) and could be reversed using beta2AR blockers. Interestingly, impaired antibody after T3 SCI could be mimicked after T9 SCI with a beta2AR agonist. These data illustrate the immunosuppressive effects of the SNS after high-level SCI and indicate that immune deficits may be overcome using beta-blockers.