Journal of neuroscience research
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Spinal cord injury (SCI) is a devastating neurological disorder, but few drugs have proven to be effective for its treatment. Neuroinflammation exaggerates the secondary injury subsequent to trauma. Emerging evidence suggests that melatonin may help protect neural tissue against secondary injury after SCI, but the underlying mechanisms remain elusive. ⋯ Melatonin increased the number of CD206+ and Arg1+ cells, decreased the number of CD16+ and iNOS+ cells and reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in the spinal cord tissue of female SCI rats. Current findings suggest that melatonin may inhibit pro-inflammatory responses and promote M2 polarization of microglial/macrophages in the spinal cord in the early stage of SCI, facilitating functional recovery. Accordingly, melatonin may represent a promising therapeutic candidate for acute SCI.
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Altered brain iron content in the striatum of premanifest and manifest Huntington's disease (HD) has been reported. However, its natural history remains unclear. This study aims to investigate altered brain iron content in premanifest and early HD, and the iron deposition rate in these patients through a longitudinal one-year follow-up test, with quantitative magnetic susceptibility as an iron imaging marker. ⋯ Such increases directly correlated with HD CAG-age product score and brain atrophy, but not with motor or cognitive scores. More importantly, a significantly higher iron deposition rate (11.9%/years in caudate and 6.1%/years in globus pallidus) was firstly observed in closer-to-onset premanifest HD and early HD as compared to the controls. These results suggest that monitoring brain iron may provide further insights into the pathophysiology of HD disease progression, and may provide a biomarker for clinical trials.
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Traumatic brain injury (TBI) results in cognitive impairment, which can be long-lasting after moderate to severe TBI. Currently, there are no FDA-approved therapeutics to treat the devastating consequences of TBI and improve recovery. This study utilizes a prodrug of 2,4-dinitrophenol, MP201, a mitochondrial uncoupler with extended elimination time, that was administered after TBI to target mitochondrial dysfunction, a hallmark of TBI. ⋯ Additionally, vehicle-treated mice had significantly lower (p = .0019) CA3 neuron count compared to sham while MP201-treated mice were not significantly different from sham levels. These results suggest that acute mitochondrial dysfunction can be targeted to impart neuroprotection from reactive oxygen species, but chronic administration may have an added benefit in recovery. This study highlights the potential for safe, effective therapy by MP201 to alleviate negative outcomes of TBI.
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Fluid percussion (FP) injury model is a popular animal model of traumatic brain injury (TBI), but still there are some issues need to be addressed. To increase the validity and reliability of this technique, we adapted the FP device using electromagnetic protractor, stainless-steel cylinder, changing pressure transducer position, and foam pads to adjust the parameters of FP pulse. Besides, the adjusted FP device is more automatic. ⋯ Further, the overall firing rates and theta powers in hippocampal CA1 were significantly reduced in TBI mice compared to sham mice at Days 2 and 3 after electrode implanting. The adapted device induced effects on behavior and biology in mice that agree with existing models. These findings confirmed the validity of adjustments, and the modified device may boost the interest in TBI studies.
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Melatonin is a neurohormone secreted from the pineal gland and has a wide-ranging regulatory and neuroprotective role. It has been reported that melatonin level is disturbed in some neurological conditions such as stroke, Alzheimer's disease, and Parkinson's disease, which indicates its involvement in the pathophysiology of these diseases. Its properties qualify it to be a promising potential therapeutic neuroprotective agent, with no side effects, for some neurological disorders. This review discusses and localizes the effect of melatonin in the pathophysiology of some diseases.