CNS neuroscience & therapeutics
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The human fetal cerebral cortex develops through a series of partially overlapping histogenetic events which occur in transient cellular compartments, such as the subplate zone. The subplate serves as waiting compartment for cortical afferent fibers, the major site of early synaptogenesis and neuronal differentiation and the hub of the transient fetal cortical circuitry. Thus, the subplate has an important but hitherto neglected role in the human fetal cortical connectome. ⋯ We review the diversity of subplate neuronal phenotypes and their involvement in cortical circuitry and discuss the complexity of late neuronal migration through the subplate as well as its potential relevance for pathogenesis of migration disorders and cortical dysplasia. While migratory neurons may become misplaced within the subplate, they can easily survive by being involved in early subplate circuitry; this can enhance their subsequent survival even if they have immature or abnormal physiological activity and misrouted connections and thus survive into adulthood. Thus, better understanding of subplate developmental history and various subsets of its neurons may help to elucidate certain types of neuronal disorders, including those accompanied by epilepsy.
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Following a traumatic brain injury (TBI), 5-50% of patients will develop posttraumatic epilepsy (PTE) with children being particularly susceptible. Currently, PTE cannot be prevented and there is limited understanding of the underlying epileptogenic mechanisms. We hypothesize that early after TBI the brain undergoes distinct cellular and synaptic reorganization that facilitates cortical excitability and promotes the development of epilepsy. ⋯ Our results demonstrate that CCI in juvenile rats rapidly induces epileptiform activity and enhanced cortical synaptic bursting. Detection of epileptiform activity early after injury suggests it may be an important pathophysiological component and potential indicator of developing PTE.
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Nerve growth factor (NGF) regulates neuronal survival and differentiation by activating extracellular signal-regulated-kinases (ERK) 1/2 and phosphoinositide-3-kinase (PI3K)/Akt pathways in two distinct processes: latency process and neurite extension process. This study was designed to investigate whether botanical drug C-glucosylated isoflavone puerarin coordinates with NGF to regulate neuritogenesis via activating ERK1/2 and PI3K/Akt in neurite extension process. ⋯ Puerarin effectively coordinated with NGF to stimulate neuritogenesis via activating ERK1/2 and PI3K/Akt pathways in neurite extension process. These results demonstrated a general mechanism supporting the therapeutic application of puerarin-related compounds in neurodegenerative diseases.
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This review highlights the recent clinical research that supports the therapeutic utility of ketamine as a multifaceted drug. After long-term use as a dissociative anesthetic, it has re-emerged as a useful agent for ameliorating pain, asthmaticus, and depression. ⋯ Chronic ketamine abuse over prolonged periods (weeks, months, and years) can produce toxicity to the gastrointestinal and urinary tract. In this review, we described the recent progress on its clinical uses and abuses.