Journal of neural transmission
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Non-neurological surgery has both acute and long-term effects on the brain. Markers for Alzheimer pathology may be used to study surgically induced neurological changes relevant for postoperative confusion, asthenia or cognitive decline. Inflammatory biomarkers, total tau (T-tau) and phosphorylated tau (P-tau) were recently shown to increase progressively in the cerebrospinal fluid (CSF) during surgery for nasal CSF leak, suggesting a neuroinflammatory response with signs of neuronal damage. ⋯ CSF T-tau and P-tau correlated significantly with the CSF/serum albumin ratios as an indicator of blood-brain barrier permeability. Findings from earlier studies showing a significant increase in biomarkers for Alzheimer's pathology during surgery were partly replicated, as neurochemical signs of impaired cortical axonal integrity during non-neurological surgery were detected. Bupivacaine may be involved in these reactions.
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Beyond the current hypothesis of depression, several new biological substrates have been proposed for this disorder. The present study investigated whether the anti-inflammatory drugs celecoxib and piroxicam have antidepressant activity in animal models of depression. After acute administration, we observed antidepressant-like effects of celecoxib (10 mg/kg) and piroxicam (10 mg/kg) in the modified forced swim test in rats. ⋯ The non-stressed celecoxib and piroxicam groups and stressed piroxicam group exhibited an increase in hippocampal superoxide dismutase activity compared with the stressed saline group. Lipid hydroperoxide was increased in the stressed group treated with vehicle and non-stressed group treated with imipramine but not in the stressed groups treated with celecoxib and piroxicam. These results suggest that the antidepressant-like effects of anti-inflammatory drugs might be attributable to enhanced antioxidant defenses and attenuated oxidative stress in the hippocampus.
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Some neurological conditions require admission to an intensive care unit (ICU) where deep sedation and mechanical ventilation are administered to improve the patient's condition. Nevertheless, these treatments are not always helpful in disease control. At this stage, deep brain stimulation (DBS) could become a viable alternative in the treatment of critical neurological conditions with long-lasting clinical benefit. ⋯ No surgical complications were observed in any of the above procedures. Neurostimulation procedures could represent a valuable choice in critical care conditions, when involuntary movements are continuous, life-threatening and refractory to intensive care procedures. DBS is feasible, safe and effective in selected cases.
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Stress-related glucocorticoids and glutamate release has been implicated in depression. Glutamate neurotoxicity is mediated, in part, by the production of nitric oxide via nitric oxide synthase (NOS) isoforms and mitochondrial damage. We previously reported that chronic social isolation stress triggers proapoptotic signaling in the rat prefrontal cortex, but not in the hippocampus. ⋯ Chronic social isolation resulted in no activation of NF-κB, but led to decreased GSH, iNOS and increased nNOS and Hsp70i levels, alterations that remained following combined stressors. Decreased mitochondrial MnSOD activity after combined stressors suggests compromised detoxifying capacity. These data indicate that Hsp70i upregulation may provide hippocampal cellular protection against chronic social isolation stress mediated by downregulation of iNOS protein expression through suppression of NF-κB activation.
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Randomized Controlled Trial Multicenter Study
A randomized, double-blind study of repeated incobotulinumtoxinA (Xeomin(®)) in cervical dystonia.
IncobotulinumtoxinA (Xeomin(®), NT 201), a preparation without accessory (complexing) proteins, has shown comparable efficacy and safety to onabotulinumtoxinA in treating cervical dystonia (CD). This study evaluated the efficacy and safety of repeated incobotulinumtoxinA injections in subjects with CD. Following a ≤20-week placebo-controlled, randomized, double-blind, single-dose main period, subjects could enter a ≤68-week prospective, randomized, double-blind, repeated-dose, flexible-interval (minimum 6 weeks) extension period with 240 U or 120 U of incobotulinumtoxinA (≤5 injections). ⋯ A major limitation of this study was the fixed dose design requested by regulatory authorities, which does not reflect clinical practice. However, repeated incobotulinumtoxinA injections (240 or 120 U; flexible intervals) provided sustained efficacy and were well tolerated, with no unexpected safety risks following repeated injections. The incidence of AEs was similar in subjects requiring repeated injections at shorter intervals (≤12 weeks) compared with those treated using longer intervals (>12 weeks).