Neuroscience
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The inflammatory response of central nervous system (CNS) and microglial activation is important in the development of pain behaviors induced by sleep deprivation. We found that chronic sleep deprivation (CSD) aggravated pain behaviors in rats with chronic pain by upregulating expression of Toll-like receptor 4 (TLR4), NOD-like receptor pyrin domain containing 3 (NLRP3), and interleukin 1β (IL-1β), which promoted microglial activation in the brain. ⋯ Inhibitors of TLR4 and NLRP3 (TAK-242 and MCC950, respectively) reduced expression levels of inflammatory factor proteins and M1-related factor mRNA, decreased microglial activation, and relieved the hyperalgesia caused by CSD. These results suggest that CSD aggravated pain behavior in rats with chronic pain through the TLR4/NLRP3/IL-1β signaling pathway, which mediates microglial activation and promotes CNS inflammation and neuronal apoptosis.
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Traumatic brain injury (TBI) is the leading cause of death in young adults and the main cause of mortality and disability across all ages worldwide. We previously analyzed the expression profile data of TBI models obtained from the Gene Expression Omnibus (GEO) database and found that the seripina3n mRNA was markedly upregulated in the acute phase of TBI in four mRNA expression profile data sets, indicating that serpina3n may be involved in the pathophysiological process of TBI. Therefore, we further investigated the biological role and molecular mechanism of serpina3n in traumatic brain injury in this study. ⋯ With the inactivation of NE, even if serpina3n was silenced, the disruption of the BBB was not further aggravated. In vitro experiments further proved that recombinant serpina3n dose-dependently inhibited the activity of recombinant NE. Based on the above, this study demonstrated that the endogenous level of sepina3n was significantly elevated in the cortex around the contusion sit after TBI in mice, which reduced the secondary blood-brain barrier disruption by inhibiting the activity of neutrophil elastase.
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MicroRNAs (miRNAs) are widely acknowledged to play a unique role in cerebrovascular disease. This research investigates the function of microRNAs in ischemic stroke via a middle cerebral artery occlusion (MCAO) model. Four differentially expressed microRNAs in rat brains were identified by bioinformatics analysis, and qRT-PCR showed that miR-423-5p exhibited the highest expression in cerebral ischemia/reperfusion injury in rats, with peak levels observed at 24 hours. ⋯ The results showed that miR-423-5p knockdown could effectively improve neurological indicators, such as cerebral infarct volume, brain water content, neurological scores, and nerve tissue damage, and inhibit the NLRP3 inflammasome, apoptosis, and oxidative stress. In contrast, the miR-423-5p mimic yielded opposite results. In conclusion, inhibition of miR-423-5p expression could effectively attenuate ischemic stroke and might be considered a promising target for stroke.
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Evidence from animal research, postmortem analyses, and magnetic resonance imaging (MRI) investigations indicate substantial morphological alteration in brain structure as a function of human immunodeficiency virus (HIV) or cocaine dependence (CD). Although previous research on HIV+ active cocaine users suggests the presence of deleterious morphological effects in excess of either condition alone, a yet unexplored question is whether there is a similar deleterious interaction in HIV+ individuals with CD who are currently abstinent. To this end, the combinatorial effects of HIV and CD history on regional brain volume, cortical thickness, and neurocognitive performance was examined across four groups of participants in an exploratory study: healthy controls (n = 34), HIV-negative individuals with a history of CD (n = 21), HIV+ individuals with no history of CD (n = 20), HIV+ individuals with a history of CD (n = 15). ⋯ While descriptively, individuals with comorbid HIV and a history of CD exhibited the lowest neurocognitive performance scores, using Principle Component Analysis of neurocognitive testing data, HIV was identified as the primary driver of neurocognitive impairment. Higher caudate volume was evident in CD+ participants relative to CD- participants. Findings indicate no evidence of compounded differences in neurocognitive function or structural measures of brain integrity in HIV+ individuals in recovery from CD relative to individuals with only one condition.
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Some studies have suggested that mitochondrial dysfunction and a superoxide imbalance could increase susceptibility to chronic stressful events, contributing to the establishment of chronic inflammation and the development of mood disorders. The mitochondrial superoxide imbalance induced by some molecules, such as rotenone, could be evolutionarily conserved, causing behavioral, immune, and neurological alterations in animals with a primitive central nervous system. ⋯ These data suggest that mitochondrial dysfunction could be an evolutionarily conserved element that induces inflammatory and behavioral changes related to chronic stress.