Neurochemistry international
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Traumatic brain injury (TBI) can lead to long-term motor and cognitive dysfunction, which can be at least partly attributed to blood-brain barrier (BBB) disruption. The mechanisms underlying post-TBI BBB disruption, however, are poorly understood thus far. Na+-K+-2Cl- cotransporter isoform 1 (NKCC1) is a universally expressed ion transporter that maintains intracellular ion homeostasis by increasing intracellular K+ and Cl-. ⋯ Bumetanide treatment markedly decreased brain water content and BBB leakage, correlated with reduction of MMP-9 expression and preventing the degradation of tight junction proteins. These findings suggest an important role of NKCC1 activation in mediating BBB disruption after TBI. Thus, NKCC1 inhibition may offer the potential for improving neurological outcomes in clinical TBI.
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Review
Targeting mitochondrial dysfunction in CNS injury using Methylene Blue; still a magic bullet?
Complex, multi-factorial secondary injury cascades are initiated following traumatic brain injury, which makes this a difficult disease to treat. The secondary injury cascades following the primary mechanical tissue damage, are likely where effective therapeutic interventions may be targeted. One promising therapeutic target following brain injury are mitochondria. ⋯ Within this mixed mini review/research article there will be a general discussion of mitochondrial bioenergetics, followed by a brief discussion of traumatic brain injury and how mitochondria play an integral role in the neuropathological sequelae following an injury. We will also give an overview of one relatively new TBI therapeutic approach, Methylene Blue, currently being studied to ameliorate mitochondrial dysfunction following brain injury. We will also present novel experimental findings, that for the first time, characterize the ex vivo effect of Methylene Blue on mitochondrial function in synaptic and non-synaptic populations of mitochondria.
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The symptoms of Parkinson's disease (PD) include motor behavioral abnormalities, which appear as a result of the extensive loss of the striatal biogenic amine, dopamine. Various endogenous molecules, including cholesterol, have been put forward as putative contributors in the pathogenesis of PD. Earlier reports have provided a strong link between the elevated level of plasma cholesterol (hypercholesterolemia) and onset of PD. ⋯ We found a significant depletion of dopamine in striatum and serotonin in cortex of hypercholesterolemic mice. The significant decrease in tyrosine hydroxylase immunoreactivity in striatum supports the observed depleted level dopamine in striatum, which is relevant to the pathophysiology of PD. In conclusion, hypercholesterolemia-induced depleted levels of cortical and striatal biogenic amines reported hereby are similar to the PD pathology, which might be associated with the observed psychomotor behavioral abnormalities.
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Alzheimer's disease (AD) is a multifactorial neurodegenerative disease and a growing health problem worldwide. Because the drugs currently used to treat AD have certain drawbacks such as single targeting, there is a need to develop novel multi-target compounds, among which oxoisoaporphine alkaloid derivatives are promising candidates. In this study, the possible anti-AD activities of 14 novel oxoisoaporphine alkaloid derivatives that we synthesized were screened and evaluated. ⋯ Next, we found that compound 8-1 could down-regulate the expression level of β-amyloid precursor protein (APP) in APPsw cells. Moreover, compound 8-1 significantly delayed paralysis in the Aβ1-42-transgenic Caenorhabditis elegans strain GMC101, which could be explained by the fact that compound 8-1 down-regulated acetylcholinesterase activity, protected against H2O2-induced acute oxidative stress and paraquat-induced chronic oxidative stress, and enhanced autophagy activity. Taken together, our data suggest that compound 8-1 could attenuate the onset and development of AD.
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Randomized Controlled Trial
The effects of omega-3 fatty acids and vitamin E co-supplementation on clinical and metabolic status in patients with Parkinson's disease: A randomized, double-blind, placebo-controlled trial.
The current research was performed to evaluate the effects of omega-3 fatty acids and vitamin E co-supplementation on clinical signs and metabolic status in people with Parkinson's disease (PD). This randomized double-blind placebo-controlled clinical trial was conducted in 60 patients with PD. Participants were randomly assigned into two groups to receive either 1000 mg omega-3 fatty acids from flaxseed oil plus 400 IU vitamin E supplements (n = 30) or placebo (n = 30) for 12 weeks. ⋯ Furthermore, co-supplementation decreased high-sensitivity C-reactive protein (hs-CRP) (-0.3 ± 0.6 vs. +0.3 ± 0.3 μg/mL, P < 0.001), and increased total antioxidant capacity (TAC) (+65.2 ± 68.7 vs. +16 ± 52.4 μmol/L, P = 0.003) and glutathione (GSH) concentrations (+41.4 ± 80.6 vs. -19.6 ± 55.9 μmol/L, P = 0.001) compared with the placebo. Additionally, co-supplementation meaningfully decreased insulin (-2.1 ± 4.9 vs. +1.4 ± 6.2 μIU/mL, P = 0.01), homeostasis model of assessment-estimated insulin resistance (-0.7 ± 1.8 vs.+0.3 ± 1.6, P = 0.02) and Beta cell function (-5.9 ± 13.9 vs. +5.7 ± 25.5, P = 0.03), and increased quantitative insulin sensitivity check index (+0.009 ± 0.02 vs. -0.006 ± 0.03, P = 0.03) compared with the placebo. Overall, our study demonstrated that omega-3 fatty acids and vitamin E co-supplementation in people with PD had favorable effects on UPDRS, hs-CRP, TAC, GSH and markers of insulin metabolism.