Brain research
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Consistent associations between the severity of neuropathic pain and cutaneous innervation have not been described. We collected demographic and clinical data, McGill Pain Questionnaires (MPQ) and skin biopsies processed for PGP9.5 and CGRP immunohistochemistry from patients with bortezomib-induced peripheral neuropathy (BiPN; n = 22), painful diabetic neuropathy (PDN; n = 16), chronic idiopathic axonal polyneuropathy (CIAP; n = 16) and 17 age-matched healthy volunteers. Duration of neuropathic symptoms was significantly shorter in patients with BiPN in comparison with PDN and CIAP patients. ⋯ Cutaneous innervation changes in BiPN confirm characteristic features of early, whereas those in CIAP and PDN are in line with late forms of neuropathic pathology. Our results allude to a distinct role for non-peptidergic nociceptors in BiPN and CIAP patients. The lack of significant associations in PDN may be caused by mixed ischemic and purely neuropathic pain pathology.
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Remote ischemic post-conditioning (RIPostC) is a technique that can protect vital organs in an indirect manner, the effects of which are exerted by the long-distance exosome-mediated transfer of functional factors. In the current study, the possible mechanism driving the function of RIPostC was explored using an in vitro system by focusing on miR-199a-5p and its downstream effectors involved in endoplasmic reticulum (ER) stress. Human umbilical vein endothelial cells (HUVECs) were administrated with hypoxia/re-oxygenation (H/R) process and exosomes were collected from the H/R-treated HUVECs. ⋯ The incubation of neural cells with exosomes suppressed cell apoptosis and inflammation, and induced the level of miR-199a-5p, which led to suppressed ER stress. Moreover, the transfection of miR-199a-5p inhibitor blocked the anti-H/R function of exosomes. Taken together, the findings outlined in the current study showed that the protection effect of HUVEC derived miR-199a-5p on neural cells was exerted via exosome transfer, which then suppressed the ER stress-induced apoptosis and inflammation by targeting BIP.
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Microglial activation plays a crucial role in the pathology of ischemic stroke. Recently, we demonstrated that fingolimod (FTY720) exerted neuroprotective effects via immunomodulation in ischemic white matter damage induced by chronic cerebral hypoperfusion, which was accompanied by robust microglial activation. In this study, we assessed the pro-angiogenic potential of FTY720 in a murine model of acute cortical ischemic stroke. ⋯ Our research indicated that FTY720 treatment promoted angiogenesis via microglial M2 polarization and exerted neuroprotection in PT ischemic stroke.
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Perioperative neurocognitive disorder (PND) is a common complication that lacks effective prevention and treatment measures. Neuroinflammation is considered to be one of the important mechanisms of PND. In this study, we investigated the effect and mechanism of anthocyanins (ANT), a natural plant ingredient, on postoperative cognition and neuroinflammation. ⋯ In addition, treatment with ANT significantly reduced neuroinflammation and microglia activation. In conclusion, MLK3 represents a novel target in surgery-induced neuroinflammation and cognitive dysfunction. ANT could inhibit the activation of MLK3 and be a promising agent for the prevention and treatment of PND.
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Innate immunity activation in the central nervous system (CNS) is known to contribute to the development of depression through NOD-like receptors containing pyrin domain 3 (NLRP3) inflammasome assembly. Furthermore, administration of agmatine (AGM), a nitric oxide synthase (NOS) inhibitor, reverses stress-induced NLRP3 inflammasome activation in rats. We examined the effects of chronically-administered nitric oxide (NO) pathway modulating drugs on NLRP1/3-mediated neuroinflammatory responses and depressive-like behaviors in chronic unpredictable mild stress (CUMS) depression model of rats. ⋯ These results suggest that both neuronal NLRP1 and microglial NLRP3 inflammasomes are involved in chronic stress-induced depressive-like behaviors. The antidepressant effects of AGM, iNOS and nNOS inhibitors are associated with the downregulation of CNS inflammasome expression levels. NO-pathway modulating drugs might provide novel therapeutic strategies for depression.