Brain research
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Tight junctions between endothelial cells of brain capillaries form the structural basis of the blood-brain barrier (BBB), which controls the exchange of molecules between blood and CNS. Regulation of cellular barrier permeability is a vital and complex process involving intracellular signalling and rearrangement of tight junction proteins. We have analysed the impact of tyrosine phosphatase inhibition on tight junction proteins and endothelial barrier integrity in a primary cell culture model based on porcine brain capillary endothelial cells (PBCEC) that closely mimics the BBB in vitro. ⋯ Cell-cell contacts of PV-treated cells appeared unaffected, and occludin proteolysis did not occur. Our results suggest that tyrosine phosphatase inhibition can influence barrier properties independent of, but also correlated to MMPs. Evidence is given for a role of MMPs in endothelial tight junction regulation at the BBB in particular and probably at tight junctions (TJs) in general.
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Corticotropin-releasing factor (CRF) plays important physiological functions in the central nervous system. The present study was performed to investigate the role of CRF and CRF receptor in nociceptive modulation in the central nucleus of amygdala (CeA) of rats. ⋯ Furthermore, the HWL to both thermal and mechanical stimulation decreased significantly after intra-CeA administration of alpha-hCRF9-41 alone, suggesting an involvement of endogenous CRF in the CeA in nociceptive modulation. The present study demonstrated that both exogenous and endogenous CRF plays an antinociceptive effect in the CeA, the effect is mediated by CRF receptor.
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After ipsilateral injections of biotinylated dextran amine (BDA) into the Kölliker-Fuse (KF) nucleus and cholera toxin B subunit (CTb) into the ventral horn in C4 to C5 segments of the spinal cord, an overlapping distribution of BDA-labeled axon terminals and CTb-labeled neurons was found in the rostral ventral respiratory group (rVRG) region ipsilateral to the injection sites. After ipsilateral injections of BDA into the KF and Fluoro-Gold (FG) into the ventral horn in C4 to C5 segments of the spinal cord, BDA-labeled axons were found to make asymmetrical synapses with the somata and dendrites of FG-labeled neurons within the neuropil of the rVRG region. ⋯ Using anterograde tracing combined with immunohistochemistry for vesicular glutamate transporter 2 (VGluT2), we further demonstrated that the KF axon terminals in the rVRG and PhN regions as well as the rVRG axon terminals in the PhN region contain VGluT2 immunoreactivity. The present results suggest that the glutamatergic pathways from the KF to the PhN directly and indirectly via the rVRG region may exist and underlie the inspiratory responses that are elicited by activation of the KF neurons.
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Hypothermia provides neuroprotection in virtually all animal models of ischemia, including adult stroke models and the neonatal hypoxic-ischemic (HI) model. In these studies, brief periods of hypothermia are examined in a neonatal model employing transient focal ischemia in a 7-day-old rat pup. Pups underwent permanent middle cerebral artery (MCA) occlusion coupled with a temporary (1 h) occlusion of the ipsilateral common carotid artery (CCA). ⋯ Therefore, both intraischemic and postischemic hypothermia provided neuroprotection in the neonatal rat, but with different effects on the degenerative time course. While there were no observable differences in simple behaviors or growth, all hypothermic conditions significantly reduced mortality rates. While the protection resulting from intraischemic hypothermia is similar to what is observed in other models, the degree of long-term ischemic protection observed after 1 h of postischemic hypothermia was remarkable and distinct from what has been observed in other adult or neonatal models.