Brain research
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We assessed whether pain-related behavior in neuropathic or control rats is changed following rapid eye movement sleep deprivation (REMSD). Furthermore, we determined the contribution of spinal glutamatergic receptors and nitric oxide to sensitivity changes following REMSD versus peripheral nerve injury. Pain behavior was assessed in Sprague-Dawley (SD) and Hannover-Wistar (HW) rats with a spinal nerve ligation or a sham operation. ⋯ The results indicate that the strain of the animals markedly influences baseline withdrawal threshold to mechanical stimulation. Mechanical hypersensitivity following REMSD, however, is similarly increased in HW and SD strains, and the REMSD-associated increase in mechanical sensitivity is independent of nerve injury. Furthermore, mechanical hypersensitivities following REMSD and peripheral nerve injury share common spinal mechanisms involving, at least, the mGluR(5) and nitric oxide.
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Lateral hemisection of the cervical (C2) spinal cord in the rat interrupts ipsilateral bulbospinal respiratory pathways arising mainly from the rostral ventral respiratory group (rVRG) and Bötzinger complex and projecting to phrenic motoneurons in C3-C5. Deafferented phrenic motoneurons can be reactivated via previously silent contralateral pathways, a process called the crossed phrenic phenomenon (CPP). In order to further characterise the neuronal bases of the CPP and quantify the neurons involved, respiratory neurons projecting to the ipsilateral phrenic nucleus in hemisected rats were labelled by injection of the monosynaptic retrograde tracer fluorogold (FG) in ipsilateral C3-C4 metamers. ⋯ This shows that phrenic motoneurons located under the C2 hemisection may still be activated by axons or collaterals of contralateral respiratory premotoneurons located in the rVRG and Bötzinger complex which cross the spinal cord midline at the level of the phrenic nuclei, and also by axon collaterals of ipsilateral rVRG premotoneurons which cross the midline both in the brainstem and in the spinal cord. Neurons with double crossing axons were twice as many in the caudal part of the rVRG (38%) compared to the part located rostrally to the area postrema (20%), which further argues in favour of a subdivision of this nucleus. These pathways may be involved in the CPP and could be differentially activated in acute or chronic lesioned rats.
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Many potential uses of direct gene transfer into neurons require restricting expression to one of the two major types of forebrain neurons, glutamatergic or GABAergic neurons. Thus, it is desirable to develop virus vectors that contain either a glutamatergic or GABAergic neuron-specific promoter. The brain/kidney phosphate-activated glutaminase (PAG), the product of the GLS1 gene, produces the majority of the glutamate for release as neurotransmitter, and is a marker for glutamatergic neurons. ⋯ Principles for obtaining long-term expression from HSV-1 vectors, based on these and other results, are discussed. Long-term glutamatergic or GABAergic neuron-specific expression may benefit specific experiments on learning or specific gene therapy approaches. Of note, promoter analyses might identify regulatory elements that determine a glutamatergic or GABAergic neuron.
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FK-506 confers a neuroprotective effect and is thought to extend the time window for thrombolytic treatment of cerebral ischemia. These effects have not been assessed in an embolic stroke model. In addition, clinical studies have raised concern that FK-506 may increase the risk of hemorrhagic transformation by damaging vascular endothelial cells. ⋯ FK-506 extended the therapeutic time window for systemic thrombolysis compared to rt-PA alone without increasing the risk for hemorrhage. Combined therapy with FK-506 salvaged some of the MRI, revealing ischemic lesions destined to infarction in the animals treated by rt-PA alone. Single low dose of FK-506 alone did not ameliorate the embolic infarction, but it did prove effective in extending the therapeutic time windows for thrombolysis without increasing the risk of hemorrhagic transformation.
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We have previously noted that the antinociceptive efficacy of morphine was significantly decreased in rat pups chronically infused with morphine from implanted osmotic minipumps. In this study, morphine was fully efficacious (i.e., 100% maximum possible effect, %MPE) in the 52 degrees C tail-immersion test after a 72-h infusion from implanted saline-filled osmotic minipumps. However, administration of up to 1000 mg/kg, s.c. morphine failed to elicit greater than a 27% MPE in rats infused with morphine at 2 mg/kg/h. ⋯ In adult rats, the mu-opioid receptor is desensitized during morphine tolerance. However, desensitization was not evident in P17 rats based on the lack of significant decreases in [(35)S]GTPgammaS binding. Furthermore, [(3)H]naloxone binding indicated a lack of mu receptor downregulation in morphine-tolerant rat pups.