Neuroscience
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To investigate intermittent theta-burst stimulation (iTBS) effect on ischemic stroke and the underlying mechanism of neurorehabilitation, we developed an ischemia/reperfusion (I/R) injury model in Sprague-Dawley (SD) rats using the middle cerebral artery occlusion/reperfusion (MCAO/r) method. Next, using different behavioral studies, we compared the improvement of the whole organism with and without iTBS administration for 28 days. We further explored the morphological and molecular biological alterations associated with neuronal apoptosis and neuroinflammation by TTC staining, HE staining, Nissl staining, immunofluorescence staining, ELISA, small RNA sequencing, RT-PCR, and western blot assays. ⋯ The target genes prediction and detection of dual-luciferase reporter genes confirmed that miR-34c-5p could inhibit neuronal apoptosis in cerebral I/R injured rats by regulating the p53/Bax signaling pathway. We also confirmed by RT-PCR and western blotting that miR-34c-5p inhibited Bax expression. In conclusion, our study supports that iTBS is vital in inhibiting neuronal apoptosis in cerebral I/R injured rats by mediating the miR-34c-5p involvement in regulating the p53/Bax signaling pathway.
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Due to the increasing needs to enhance our cognitive performance, and decrease fatigue with increasing number of tasks in our everyday life, it's interesting to study whether a small amount of active substance present in dietary supplements, is enough to impact cognition. We investigated an acute effect of an energy dietary supplement containing low amount of caffeine (55 mg) and other stimulatory ingredients by means of a resting state EEG in a double blind, placebo controlled study (N = 47, 27 women). The use of a nonparametric cluster-based permutation analysis allowed us to observed a significant group × block interaction effect after 90 minutes post-ingestion (P = 0.022 cluster corrected) in the 'eyes closed' condition, i.e. an increase in normalized rsEEG power in the placebo group, which was abolished in the study group. ⋯ Similar trend but without significant effect was found in the 'eyes open' condition. Our results suggest that low caffeine content dietary supplementation acts as a reversal of the fatigue-related brain activity in the neural networks active in the resting state. These findings not only may help to clarify previous nonconclusive findings, but more importantly, show that an ingestion of caffeinated stimulants before neurocognitive examinations, both in research and diagnostics, should be taken into account, as they may influence cognition, even in small doses and when the effects are absent in the behavioral measures.
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Pain after spinal cord injury (SCI) can be difficult to treat. Drugs that target the opioid receptor (OR) outside the central nervous system (CNS) have gained increasing interest in pain control owing to their low risk of central side effects. Asimadoline and ICI-204448 are believed to be peripherally restricted KOR agonists withlimited access to the CNS. ⋯ High-dose ICI-204448 (10 mg/kg, s.c.) attenuated the increased fluorescence intensity of lumbar DRG neurons activated by a noxious pinch (400 g) stimulation in SCI mice. In conclusion, systemic administration of ICI-204448 achieved SCI pain inhibition at doses that did not induce notable side effects and attenuated DRG neuronal excitability which may partly contribute to its pain inhibition. These findings suggest that peripherally restricted KOR agonists may be useful for treating SCI pain, but the therapeutic window must be carefully examined.
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Sonogenetics is preferred for neuroregulation and the treatment of brain diseases due to its noninvasive properties. Ultrasonic stimulation produces thermal and mechanical effects, among others. Since transient receptor potential vanilloid 1 (TRPV1) could be activated at 42 °C, it is overexpressed in the M1 region of the mouse motor cortex to sense the change of temperature upon being stimulated by focused ultrasound. ⋯ Furthermore, when the temperature is >42 °C, the peak-to-peak value of the EMG signal for mice with TRPV1 overexpression in the M1 region was higher than that for mice without TRPV1 overexpression. The immunohistochemical results showed that ultrasound was not harmful to the stimulation site. The noninvasive ultrasound stimulation combined with thermosensitive protein TRPV1 overexpressed in neurocytes as sonothermogenetics technology has great potential to be used for the treatment of neurological diseases.