Brain research
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The endogenous opioid enkephalin is known to inhibit spinal nociceptive transmission. Here we investigated activation of spinal enkephalinergic neurons by determining the proportions of c-Fos expressing (activated) spinal neurons that were enkephalinergic after different acute and chronic peripheral nociceptive stimuli. The number of c-Fos-activated neurons in the dorsal horn was increased after hind paw injection of capsaicin, formalin or complete Freund's adjuvant (CFA, 1.5 hrs - 4 days). ⋯ Combining all acute (=2 hrs) versus chronic (≥20 hrs) treatment groups, there was a significant decrease in the percentage of activated neurons that were enkephalinergic in superficial layers, but a significant increase in the deeper layers of the dorsal horn in the chronic treatment group. It is concluded that the overall percentage of c-Fos activated neurons that contained enkephalin was not significantly different between acute and chronic pain phases. However, the shift in localization of these neurons within the spinal dorsal horn indicates a noxious stimulus directed activation pattern.
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Focal cerebral infarction causes secondary damage in the ipsilateral ventroposterior thalamic nucleus (VPN). Chondroitin sulfate proteoglycans (CSPGs) are a family of putative inhibitory components, and its degradation by chondroitinase ABC (ChABC) promotes post-injury neurogenesis. This study investigated the role of ChABC in the primary and secondary injury post stroke in hypertension. ⋯ The expressions of CSPGs, growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were detected with immunofluorescence or Western blotting. The intra-infarct infusion of ChABC, by degrading accumulated CSPGs, rescued neuronal loss and increased the levels of GAP-43 and SYN in both the ipsilateral cortex and VPN, indicating enhancd neuron survival as well as augmented axonal growth and synaptic plasticity, eventually improving overall neurological function. The study demonstrated that intra-infarct ChABC infusion could salvage the brain from both primary and secondary injury by the intervention on the neuroinhibitory environment post focal cerebral infarction.
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Early recovery from incomplete spinal cord contusion is improved by prolonged stimulation of the hindbrain's serotonergic nucleus raphe magnus (NRM). Here we examine whether increases in cyclic adenosine monophosphate (cAMP), an intracellular signaling molecule with several known restorative actions on damaged neural tissue, could play a role. Subsequent changes in cAMP-dependent phosphorylation of protein kinase A (PKA) and PKA-dependent phosphorylation of the transcription factor "cAMP response element-binding protein" (CREB) are also analyzed. ⋯ The phosphorylated fraction of PKA (pPKA) and CREB (pCREB) was reduced significantly in all three regions after SCI and restored by NRM stimulation, except for pCREB in lumbar segments. In conclusion, SCI produces spreading deficits in cAMP, pPKA and pCREB that are reversible by Gs protein-coupled 5-HT receptors responding to raphe-spinal activity, although these signaling molecules are not reactive to NRM stimulation in normal tissue. These findings can partly explain the benefits of NRM stimulation after SCI.
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Convincing evidence indicates that inflammation contributes to the adverse prognosis of subarachnoid hemorrhage (SAH). Some pro-inflammatory molecules such as high mobility group protein 1, S100 family of proteins, β-amyloid peptide, and macrophage antigen complex 1 have been involved in the damaging inflammation process following SAH. The receptor for advanced glycation end-products (RAGE) is a transmembrane receptor that senses these molecules and plays central role in inflammatory processes. ⋯ Moreover, there was a significant positive correlation between the expression of RAGE and that of p65 protein. Double immunofluorescence staining showed that RAGE was expressed by neuron and microglia rather than astrocyte after SAH. These results suggest that RAGE may be directly involved in the inflammatory response after SAH, and there might be important implications for further studies using specific RAGE antagonists to decrease inflammation-mediated brain injury following SAH.
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The brain is treated as a nested hierarchical complex system with substantial interactions across spatial scales. Local networks are pictured as embedded within global fields of synaptic action and action potentials. Global fields may act top-down on multiple networks, acting to bind remote networks. ⋯ The resulting models are transparently related to several EEG and steady state visually evoked potentials correlated with cognitive states, including estimates of neocortical coherence structure, traveling waves, and standing waves. The global models suggest that global oscillatory behavior of self-sustained (limit-cycle) modes lower than about 20 Hz may easily occur in neocortical/white matter systems provided: Background cortical excitability is sufficiently high; the strength of long cortico-cortical axon systems is sufficiently high; and the bottom-up influence of local networks on the global dynamic field is sufficiently weak. The global models provide “entry points” to more detailed studies of global top-down influences, including binding of weakly connected networks, modulation of gamma oscillations by theta or alpha rhythms, and the effects of white matter deficits.