Brain research
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Translocator protein 18 kDa (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is predominantly located in the mitochondrial outer membrane and plays an important role in steroidogenesis, immunomodulation, cell survival and proliferation. Previous studies have shown an increased expression of TSPO centrally in neuropathology, as well as in injured nerves. TSPO has also been implicated in modulation of nociception. ⋯ The TSPO agonist Ro5-4864, given intrathecally, dose-dependently retarded or prevented the development of mechanical allodynia and thermal hyperalgesia in rats with CFA-induced monoarthritis. These findings provide evidence that spinal TSPO is involved in the development and maintenance of inflammatory pain behaviors in rats. Thus, spinal TSPO may present a central target as a complementary therapy to reduce inflammatory pain.
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Angiotensin II (Ang II) receptor blockade is beneficial in stroke, possibly due to attenuation of vascular oxidative stress. Mice genetically targeted for the superoxide-forming vascular NADPH oxidase subunit, NOX1, have a blunted hypertensive response to Ang II. We therefore hypothesised that NOX1 is mechanistically involved in Ang II-induced superoxide production by cerebral arteries, and potentially in stroke outcome. ⋯ However, cortical infarct volume (which was very modest in WT) was approximately 4-fold greater in brains of NOX1-KO versus WT. Thus, NOX1 is essential for superoxide production in large cerebral arteries in response to Ang II but not under basal conditions. Furthermore, NOX1 does not appear to contribute to stroke size, and it may limit cortical infarct development following cerebral ischemia.
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The left parietal cortex contributes to goal-directed hand movement. In this study, we targeted this region with transcranial magnetic stimulation (TMS) to assess the effects on a wider distributed circuitry related to motor control. Ten healthy subjects underwent 3 Tesla functional magnetic resonance imaging (fMRI) with interleaved TMS. ⋯ Movement imagery after TMS showed significantly increased activation in the left medial prefrontal cortex, right lateral prefrontal cortex, left supramarginal gyrus and right occipital cortex, while a decrease was present in bilateral anterior parietal cortex (P<0.01 voxel-level; P<0.05 volume corrected). Activation changes after TMS of left superior parietal cortex thus appears to increase prefrontal and posterior parietal cortex activation, associated with a reduced function of the anterior parietal cortex, including S2. These changes are thought to reflect an impaired ability to estimate the proprioceptive consequences of movement during its preparation, which is compensated by the increased contribution of more remote parietal and prefrontal cortical regions.
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An important factor in determining the adverse consequences of a stress experience is the degree to which an individual can exert control over the stressor. Stressor controllability is known to influence brain norepinephrine levels, but its impact on activity in noradrenergic cell bodies is unknown. In the present study we investigated whether noradrenergic neurons within the locus coeruleus (LC), the major source of forebrain norepinephrine, are sensitive to stressor controllability. ⋯ Again we detected an overall effect of stress, which did not differ between controllable and uncontrollable stress. We conclude that exposure to stress robustly increases expression of TH and c-fos in the LC, but this effect is not influenced by stressor controllability. To the extent that the expression of these genes reflects degree of neuronal activation, our results suggest that stress-induced activity of noradrenergic cell bodies in the LC is not sensitive to stressor controllability.
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Patients who have suffered nerve injury show profound inter-individual variability in neuropathic pain even when the precipitating injury is nearly identical. Variability in pain behavior is also observed across inbred strains of mice where it has been attributed to genetic polymorphisms. Identification of cellular correlates of pain variability across strains can advance the understanding of underlying pain mechanisms. ⋯ Following nerve injury, the residual mRNA levels of Na(v)1.6 (downregulated in two of the strains) correlated tightly to the extent of autotomy behavior. A suggestive correlation was also seen for the post-injury mRNA levels of Contactin (downregulated in all strains) with autotomy. Thus, our results suggest a contribution by DRG Na(v)1.6, and possibly Contactin to neuropathic pain in the neuroma model in mice.