Neuroscience
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Increasing age is associated with a poor prognosis following traumatic brain injury (TBI). CNS axons may recover poorly following TBI due to expression of myelin-derived inhibitors to axonal outgrowth such as Nogo-A. To study the role of Nogo-A/B in the pathophysiological response of the elderly to TBI, 1-year-old mice deficient in Nogo-A/B (Nogo-A/B homozygous(-/-) mice), Nogo-A/B heterozygous(-/+) mice, and age-matched wild-type (WT) littermate controls were subjected to a controlled cortical impact (CCI) TBI. ⋯ Neither TBI nor the absence of NogoA/B caused an increased A beta expression. Myelin staining showed a reduced area and density in the corpus callosum in brain-injured Nogo-A/B(-/-) animals compared to their littermate controls. These novel and unexpected behavioral results demonstrate that the absence of Nogo-A/B may negatively influence outcome, possibly related to hypomyelination, following TBI in mice and suggest a complex role for this myelin-associated axonal growth inhibitor following TBI.
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Symptomatic ischemia following aneurysmal subarachnoid hemorrhage (SAH) is common but poorly understood and inadequately treated. Severe constriction of the major arteries at the base of the brain, termed vasospasm, traditionally has been thought to be a proximal event underlying these ischemias, although microvascular changes also have been described. The vast majority of studies aimed at understanding the pathogenesis of ischemic deficits, and vasospasm have focused on the interaction of the "spasmogen" of the extravasated blood with the smooth muscle and endothelium of the arteries. ⋯ Focal application of a GABA(A) receptor agonist and antagonist was used to respectively inactivate and activate the RVM. We show here that the RVM modulates cerebral blood flow under resting conditions, and further, contributes to restoration of cerebral perfusion following a high-grade SAH. Failure of this brainstem compensatory mechanism could be significant for acute perfusion deficits seen in patients following subarachnoid hemorrhage.
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Morphine sensitization is a model of latent, functionally inducible increase in dopamine D(1) receptor-mediated transmission, which may be unmasked by an external stimulus. Morphine-sensitized rats present dopamine D(1) receptor-dependent stereotypies upon morphine challenge and resilience to unavoidable stress-induced behavioral deficits. This tonic increase in dopamine D(1) dopaminergic transmission is counter-adaptive to an enhanced mu-opioid receptor-dependent signaling in striatal areas. ⋯ The stress-induced neurochemical modifications and their sensitivity to receptor antagonists were similar to those observed after acute morphine administration. In conclusion, these results suggest that in the experimental conditions used an increase in dopamine output in striatal areas is followed by a complex neurochemical pattern, in which the initial stimulation of dopamine D(1) receptors triggers a sequence of signaling events that lead to an mGluR(5)-mediated increase in phospho-Thr75 DARPP-32 levels. Since DARPP-32 phosphorylated in Thr75 inhibits cAMP-dependent protein kinase (PKA) activity, the final result is a decrease in the dopamine D(1) receptor-dependent phosphorylation events.