Journal of neuroscience research
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The financial and emotional cost of caring for children affected by hypoxic-ischemic encephalopathy (HIE) is enormous, and developing therapeutic strategies to prevent or ameliorate the severity of HI-related brain injury remains a major priority. In the past, supportive management was the mainstay of treatment, but considerable progress has been made in identifying and developing neuroprotective strategies for neonates with HIE. The neuroprotective effects of several therapeutic modalities, including anticonvulsants, hyperbaric oxygen, and erythropoietin, have been investigated. ⋯ The pathogenesis of HIE involves more than one pathway, and intervening in multiple pathways may yield better results than interventions targeted at a single cellular level. The therapeutic benefits of xenon and hypothermia have been confirmed in several in vitro and in vivo studies, both individually and in combination. With promising results being reported, it is, perhaps, only a matter of time before xenon and hypothermia become established as a standard care for neonates with HIE.
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Blast-induced neurotrauma (BINT) leads to deterioration at the cellular level, with adverse cognitive and behavioral outcomes. The nucleus accumbens (NAC) plays an important role in reward, addiction, aggression, and fear pathways. To identify the molecular changes and pathways affected at an acute stage in the NAC, this study focused on a time course analysis to determine the effects of blast on neurochemical and apoptotic pathways. ⋯ In addition, increased levels of caspase-3, an apoptotic marker, confirm active cell death in NAC. It is hypothesized that blast overpressure causes inflammation and neurochemical changes that trigger apoptosis in NAC. This cascade of events may lead to stress-related behavioral outcomes and psychiatric sequelae.
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Peripheral nerve injury induces the cleavage of CX3CL1 from the membrane of neurons, where the soluble CX3CL1 subsequently plays an important role in the transmission of nociceptive signals between neurons and microglia. Here we investigated whether CX3CL1 regulates microglia activation through the phosphorylation of extracellular signal-regulated protein kinase 5 (ERK5) in the spinal cord of rats with spinal nerve ligation (SNL). ERK5 and microglia were activated in the spinal cord after SNL. ⋯ The blockage of CX3CR1, the receptor of CX3CL1, significantly reduced the level of ERK5 activation following SNL. In addition, the antisense knockdown of ERK5 reversed the CX3CL1-induced hyperalgesia and spinal microglia activation. Our study suggests that CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through the ERK5 signaling pathway.