Manganese (Mn) is a potent neurotoxin known to cause long-lasting structural damage and progressive cognitive deficits in the brain. However, new therapeutic approaches are urgently needed since current treatments only target symptoms of Mn exposure. Recent studies have suggested a potential role for multipotent neural stem cells (NSCs) in the etiology of Mn-induced cognitive deficits. In this study, we evaluated the effect of direct intracerebral transplantation of NSCs on cognitive function of mice chronically exposed to MnCl2, and further explored the distribution of transplanted NSCs in brain tissues. NSCs were isolated and bilaterally injected into the hippocampal regions or lateral ventricles of Mn-exposed mice. The results showed that many transplanted cells migrated far away from the injection sites and survived in vivo in the Mn-exposed mouse brain, implying enhanced neurogenesis in the host brain. We found that NSCs transplanted into either the hippocampal regions or the lateral ventricles significantly improved spatial learning and memory function of the Mn-exposed mice in the Morris water maze. Immunofluorescence analyses indicated that some surviving NSCs differentiated into neurons or glial cells, which may have become functionally integrated into the impaired local circuits, providing a possible cellular basis for the improvement of cognitive function in NSC-transplanted mice. Taken together, our findings confirm the Mn-induced impairment of neurogenesis in the brain and underscore the potential of treating Mn exposure by NSC transplantation, providing a practical therapeutic strategy against this type of neurotoxicity.

BackgroundThis retrospective clinical investigation aimed to evaluate the short-term effectiveness and safety of SBCAS for symptomatic bilateral high-grade CS.Material/MethodsFrom 2009 to 2014, 145 patients were recruited. Among them, 70 underwent SBCAS, and other 75 patients underwent SAMM and served as controls. The immediate postprocedural complications and postprocedural neurological evaluation, as well as restenosis at 6-month and 1-year follow-ups in the SBCAS group are reported. Additionally, baseline risk factors for ischemic stroke, adverse effects of drugs, and outcomes at 30-day, 6-month, and 1-year follow-ups were compared between the 2 groups.ResultsOur data did not reveal significant differences between the 2 groups in baseline risk factors for ischemic stroke. In the SBCAS group, both HPS (5.7%) and HD (40%) occurred, but they were not very severe, and no patients had postprocedural neurological deficit. Moreover, restenosis only occurred in 3 patients at 3 stent placement sites (4.3%) at 1-year follow-up. Adverse effects of drugs did not occur in SBCAS group, but adverse effects of Bayer aspirin and Lipitor occurred in 4 patients (5.4%) and 18 patients (24.3%), respectively, at 6-month follow-up in the control group. Furthermore, there were significant differences in outcomes between the 2 groups at 30-day, 6-month, and 1-year follow-ups, in that NIHSS, CS ratio, and incidence of endpoint events, as well as 1-year cumulative probability of endpoint events, were all lower in the SBCAS group than in the control group (p<0.05).ConclusionsCompared to SAMM, we found that SBCAS was more effective and safer for symptomatic bilateral high-grade CS.

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