Neuroscience
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The glymphatic system is important for waste removal in the central nervous system. It removes soluble proteins and metabolic waste under the action of aquaporin-4 (AQP4) at the end of astrocytes. The glymphatic system plays a role in numerous neurological diseases; however, the relationship between migraine and the glymphatic system remains unclear. ⋯ Then, further suppression of glymphatic function by TGN-020 (an AQP4 blocker) aggravated the migraine pathological changes in mice. The results indicated that glymphatic dysfunction may aggravate migraine pathology. Therefore, our findings revealed the potential role of the glymphatic system in migraine, providing possible targets for migraine prevention and treatment.
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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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Morphine has a strong analgesic effect and is suitable for various types of pain, so it is widely used. But long-term usage of morphine can lead to drug tolerance, which limits its clinical application. The complex mechanisms underlying the development of morphine analgesia into tolerance involve multiple nuclei in the brain. ⋯ Existing studies show that dopamine receptors and μ-opioid receptors participate in morphine tolerance through the altered activities of dopaminergic and/or non-dopaminergic neurons in the VTA. Several neural circuits related to the VTA are also involved in the regulation of morphine analgesia and the development of drug tolerance. Reviewing specific cellular and molecular targets and related neural circuits may provide novel precautionary strategies for morphine tolerance.
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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.