Journal of molecular neuroscience : MN
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Human umbilical cord blood (HUCB) transplantation has become an alternative cell therapy for hematological and oncological malignancies in the clinic and is considered for neurological disorders. The heterogeneity in the content of the different stem and progenitor cells composing HUCB mononuclear cells (MNC) may influence their engraftment and neurotherapeutic effect. We hypothesized that CD45 pan-hematopoietic marker expression is heterogeneous in MNC, and therefore, CD45+ subpopulation enrichment for neurotherapy may provide a tool to overcome cellular variance in different HUCB units. ⋯ Neurotherapeutic effects, evaluated with an established neurological severity score and novel object recognition test, indicated improved functional motor and memory recovery and found independent of delivery type. Cytokine analysis in extracts of TBI brain cortices indicated an acute immunomodulatory effect by HUCB CD45+ subpopulation upon xenotransplantation. These results may provide insights to CD45 marker as a predictor of HUCB units' quality for neurotherapy in TBI.
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Recent clinical studies have revealed sex differences in response to transient receptor potential vanilloid 1 (TRPV1) agonist-induced pain. However, the mechanism of these differences in TRPV1-related chronic pain remains unclear. In the present study, we investigate the effects of inflammation and gonadal hormones on TRPV1 expression in trigeminal ganglia. ⋯ Furthermore, tamoxifen was unable to inhibit the upregulation of TRPV1 expression in OVX female and ODX male rats after CFA injection. In summary, these data indicate that gender differences in TRPV1 function may be, in part, mediated by sex-dependent TRPV1 expression in sensory ganglia. Testosterone plays a key role in the inhibition of TRPV1 expression in this rat chronic inflammatory pain model.
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Carbon monoxide-releasing molecule (CORM-2) acts as a carbon monoxide (CO) deliverer in a more controlled manner without altering carboxyhemoglobin level and exerts potential function in inhibiting inflammation and/or acute nociception. However, the regulatory mechanism of CORM-2 on spinal nerve ligation (SNL)-induced neuropathic pain is not currently clear. Our study aims to investigate the role of CORM-2 in neuropathic pain and the underlying mechanism. ⋯ Moreover, exogenous CORM-2 could attenuate HO-1 expression, while overexpressed heme oxygenase-1 (HO-1) increased intracellular CO production, attenuated Cx43 expression, hemichannel function, and gap junction function on spinal astrocyte membranes. Additionally, Cx43 over-expression markedly reduced CORM-2-induced mechanical threshold and thermal hyperalgesia and elevated CORM-2-induced spontaneous EPSC frequency. In conclusion, CORM-2 attenuated SNL-induced neuropathic pain via suppressing Cx43-hemichannel function, which may contribute to understanding of the pathology of neuropathic pain.
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The role of microRNAs (miRNAs) in the regulation of nerve injury-induced neuropathic pain is unclear. The aims of this study were to assess and compare miRNA expression profiles in dorsal root ganglia (DRG) following three different kinds of peripheral nerve injury, including spinal nerve ligation (SNL), dorsal root transection (DRT), and ventral root transection (VRT), in Sprague-Dawley rats. Responses to thermal and mechanical stimuli were measured preoperatively and on postoperative days (PODs) 1, 4, and 7. ⋯ Of the four miRNAs that were mutually aberrant in all three models, two were significantly upregulated (twofold), miR-21 and miR-31, and two were significantly downregulated, miR-668 and miR-672. Using in situ hybridization, miRNA-21, miRNA-31, miRNA-668, and miRNA-672 were found to localize to neurons in the DRG. Collectively, the mutual abnormal miRNA expression of miR-21, miR-31, miR-668, and miR-677 implied that these miRNAs may be therapeutic targets for alleviating multiple forms of neuropathic pain.
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Cerebral cavernous malformations (CCMs) are vascular malformations mostly located within the central nervous system. Heterozygous loss of function mutations in CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10 genes are identified in about 90 % of familial cases of CCMs and two thirds of sporadic cases with multiple lesions. In this study, we performed genetic screening of a cohort of 31 patients, mainly pediatric. ⋯ In conclusion, the penetrance of CCM mutations in familial pediatric cases is high (85 %). The genetic workup could improve clinical and genetic counseling in CCM patients. Moreover, we confirmed the high risk of hemorrhage in children with CCMs.