Neuroscience
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Cell swelling usually initiates the regulatory volume decrease (RVD) process mediated mainly by volume-regulated anion channels (VRACs), which are formed by multiple different leucine-rich repeat-containing protein 8 (LRRC8) family members. VRAC currents have been widely recorded in astrocytes, neurons and microglia in the brain, and VRACs have been suggested to be involved in the important pathogenesis of cell swelling-related central nervous system (CNS) diseases, such as ischemic stroke, epilepsy and epileptogenesis, glioblastoma (GBM), and so on. ⋯ After cerebral ischemia, the swollen astrocytes, neurons and microglia can activate LRRC8A-dependent VRACs, which may respectively promote the release of excitatory amino acids (EAA), interaction with ionotropic glutamate receptors, and regulating inflammation, suggesting the pleiotropic roles of LRRC8A in swollen brain cells. For the treatment of cell swelling-related CNS diseases, specific targeting LRRC8A may be a superior strategy to inhibit swollen-induced VRAC hyperactivity without blocking the normal VRAC function.
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There has been increasing interest in the measurement and comparison of activity across compartments of the pyramidal neuron. Dendritic activity can occur both locally, on a single dendritic segment, or globally, involving multiple compartments of the single neuron. ⋯ However, the distinction between local and global activity made by calcium imaging requires careful consideration. In this review we describe local and global activity, discuss the difficulties and caveats of this distinction, and present the evidence of local and global activity in information processing and behavior.
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Epilepsy is a neurological disorder with a high prevalence worldwide. Several studies carried out during the last decades indicate that the administration of cannabinoids as well as the activation of the endocannabinoid system (ECS) represent a therapeutic strategy to control epilepsy. ⋯ The present review is focused to present findings supporting this issue. According to the current discrepancies, it is relevant to elucidate the different effects induced by the activation of ECS and determine the conditions under which it facilitates the seizure activity.
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Spinal cord injury (SCI) is a central nervous system trauma that can cause severe neurological impairment. A series of pathological and physiological changes after SCI (e.g., inflammation, oxidative stress, apoptosis, and mitochondrial dysfunction) promotes further deterioration of the microenvironment at the site of injury, leading to aggravation of neurological function. ⋯ A comprehensive understanding of the function and regulatory mechanism of Nrf2 in the pathophysiology of SCI will aid in the development of targeted therapeutic strategies for SCI. This review discusses the roles of Nrf2 in SCI, with the aim of aiding in further elucidation of SCI pathophysiology and in efforts to provide Nrf2-targeted strategies for the treatment of SCI.
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We previously showed that both open-loop (beat of a metronome) and closed-loop (phase-dependent tactile feedback) cueing may be similarly effective in reducing Freezing of Gait (FoG), assessed with a quantitative FoG Index, while turning in place in the laboratory in a group of people with Parkinson's disease (PD). Despite the similar changes on the FoG Index, it is not known whether both cueing responses require attentional control, which would explain FoG Index improvement. The mechanisms underlying cueing responses are poorly understood. ⋯ The interaction of the salience network and retrosplenial-temporal networks was the best predictor of responsiveness to open-loop cueing, presenting the largest effect size (d = 1.16). The interaction between the salience network and subcortical as well as cingulo-parietal and subcortical networks were the strongest predictors of responsiveness to closed-loop cueing, presenting the largest effect sizes (d = 1.06 and d = 0.84, respectively). Salience network activity was a common predictor of responsiveness to both cueing, which suggests that auditory and proprioceptive stimuli during turning may require some level of cognitive and insular activity, anchored within the salience network, which explain FoG Index improvements in people with PD.