Brain research
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The retrograde tracer cholera toxin beta-subunit (CTB) was used to trace long ascending propriospinal projections from neurons in the lumbosacral spinal cord to the upper cervical (C3) gray matter in adult male Sprague-Dawley rats. Following large 0.5 microl CTB injections restricted mainly to the upper cervical ventral horn (n=5), there were many lumbosacral CTB-positive neurons (14-17/section) in the intermediate gray and ventral horn (dorsal lamina VIII, medial VII extending into X) contralaterally, with fewer at corresponding ipsilateral locations. Labeled cells (4-8/section) were also observed in contralateral laminae IV-VI and the lateral spinal nucleus, with fewer ipsilaterally. ⋯ These results suggest direct projections from ventromedially located neurons of lumbar and sacral segments to the contralateral ventral gray matter of upper cervical segments, as well as from neurons in the intermediate but not superficial dorsal horn. They further suggest that some lumbosacral superficial dorsal horn neurons project to the upper cervical dorsal horn. These propriospinal projections may be involved in coordinating head and neck movements during locomotion or stimulus-evoked motor responses.
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LPA (lysophosphatidic acid) specific endothelial differentiation gene (EDG) receptors have been implicated in various anti-apoptotic pathways. Ischemia of the brain and retina causes neuronal apoptosis, which raises the possibility that EDG receptors participate in anti-apoptotic signaling in ischemic injury. We examined the expression of EDG receptors in a model of retinal ischemia-reperfusion injury and also tested LXR-1035, a novel analogue of LPA, in the rat following global retinal ischemic injury. ⋯ We found that the normal retina has a baseline expression of the LPA receptors, EDG-2 and EDG-4, which are significantly upregulated in the inner layers in response to ischemia. Animals pretreated with LXR-1035 had dose-dependent, significant reductions in histopathologic damage and significant improvement in functional deficits compared with corresponding vehicle-controls, after 45 and 60 min of ischemia. These results suggest that LPA receptor signaling may play an important role in neuroprotection in retinal ischemia-reperfusion injury.
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Hypoxic-ischemic injury in term neonates remains a significant cause of long-term neurological morbidity. The post-natal day 10 (P10) mouse is accepted as a model for the term human. This study was designed to assess the relationships between the duration of hypoxia-ischemia (HI) on P10 and the structural and functional neurological deficits that appear in the adult mouse as a consequence. ⋯ After correcting for motor deficits, there is evidence for persistence of "cued" learning but not spatial learning with increasing hypoxia-ischemia time on P10 in this model system.
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Clonidine, a specific alpha2-adrenergic receptor agonist, has been found to be effective for the treatment of neuropathic pain, the mechanism underlying the effect is, however, not well understood. Here, the effect of clonidine on long-term potentiation (LTP) of C-fiber evoked field potentials in spinal dorsal horn, which is a synaptic model of injury-induced hyperalgesia, was investigated. ⋯ We found that (1) Clonidine completely blocked LTP induction, when applied 30 min before tetanic stimulation and depressed spinal LTP, when applied 30 min and 3 h after LTP induction. (2) The inhibitory effect of clonidine on spinal LTP had two phases: a fast phase lasting for about 3.5 h and a slow phase persisting for the rest time of experiments (up to 8 h after drug). (3) Spinal clonidine at low dose (10.7 micro g/100 micro l) depressed spinal LTP but not C-fiber baseline response and at higher dose (107 micro g/100 micro l) depressed both of them. (4) Pretreatment with alpha2-adrenergic receptor antagonist yohimbine completely blocked the inhibitory effect of clonidine. (5) Pretreatment with muscarinic receptor antagonist atropine, nitric oxide synthesis inhibitor l-NNA or cGMP inhibitor ODQ depressed the fast phase inhibition significantly and abolished the slow phase inhibition completely. These results suggest that clonidine may exert analgesic effect by depressing the synaptic plasticity in spinal dorsal horn, via activation of muscarinic receptor-NO-cGMP pathway.
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This study investigates the antinociceptive effect of intracerebroventricular (i.c.v.) injection of cytidine-5'-diphosphate choline (CDP-choline; citicoline) and the involvement of cholinergic mechanisms in rats. Three different pain models were utilized: thermal paw withdrawal test, mechanical paw pressure test and acetic acid writhing test. The i.c.v. administration of CDP-choline (0.5, 1.0 and 2.0 micromol) produced dose and time-dependent antinociception. ⋯ CDP-choline did not impair the motor performance of rats as evaluated by a rota-rod test. Therefore, it can be postulated that CDP-choline exerts an antinociceptive effect mediated by a central cholinergic mechanism. Activation of specific alpha(7)-nicotinic cholinergic receptors through the activation of presynaptic cholinergic mechanisms appears to be involved in the antinociceptive effect of this drug.