Brain research bulletin
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Brain research bulletin · Jun 2018
Hydroxysafflor yellow a protects brain microvascular endothelial cells against oxygen glucose deprivation/reoxygenation injury: Involvement of inhibiting autophagy via class I PI3K/Akt/mTOR signaling pathway.
The present study aimed to test whether Hydroxysafflor yellow A (HSYA) protects the brain microvascular endothelial cells (BMECs) injury induced by oxygen glucose deprivation/reoxygenation (OGD/R) via the PI3K/Akt/mTOR autophagy signaling pathway. Primary rat BMECs were cultured and identified by the expression of factor VIII-related antigen before being exposed to OGD/R to imitate ischemia/reperfusion (I/R) damage in vitro. The protective effect of HSYA was evaluated by assessing (1) cellular morphologic and ultrastructural changes; (2) cell viability and cytotoxicity; (3) transendothelial electrical resistance (TEER) of monolayer BMECs; (4) cell apoptosis; (5) fluorescence intensity of LC3B; (6) LC3 mRNA expression; (7) protein expressions of LC3, Beclin-1, Zonula occludens-1 (ZO-1), phospho-Akt (p-Akt), Akt, phospho-mTOR (p-mTOR) and mTOR. ⋯ Mechanistic studies revealed that HSYA (80 μM) markedly increased the levels of p-Akt and p-mTOR proteins. Blockade of PI3K activity by ZSTK474 abolished its anti-autophagic and pro-survival effect and lowered both Akt and mTOR phosphorylation levels. Taken together, these results suggest that HSYA protects BMECs against OGD/R-induced injury by inhibiting autophagy via the Class I PI3K/Akt/mTOR signaling pathway.
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Brain research bulletin · May 2018
Pirouetting pigs: A large non-primate animal model based on unilateral 6-hydroxydopamine lesioning of the nigrostriatal pathway.
The rotating 6-hydroxydopamine (6-OHDA) rat model has long been important when developing new treatment strategies for Parkinson's disease (PD). Similar non-human primate models have been developed for translational research purposes as large animal models are required by regulatory bodies as an intermediate "phase 0" trial step. However, experimental research in non-human primates encounters several economical and regulatory issues, which may be avoided by the alternative use of pigs as a large animal model for experimental brain research. ⋯ Female Göttingen minipigs are susceptible to unilateral dopaminergic degeneration when properly injected unilaterally with sufficient amounts of 6-OHDA in the nigrostriatal pathway. The location of the 6-OHDA injections and thus the accuracy of the employed stereotaxy can be verified in vivo using MRI postoperatively. The injected minipigs display unilateral parkinsonism with a well-defined rotational response to amphetamine that may be ameliated by STN-DBS performed on the lesioned side. The response to apomorphine was, however, not consistent, illustrating that further work on this promising non-primate large animal model is needed, before it is fully similar to the established 6-OHDA models in other species.
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Brain research bulletin · May 2018
Electroacupuncture restores hippocampal synaptic plasticity via modulation of 5-HT receptors in a rat model of depression.
The study aimed to determine the effect of electroacupuncture (EA) on Wistar Kyoto (WKY) depressive model rats and explore the possible mechanism of EA on hippocampal CA1 region neuronal synaptic plasticity. ⋯ EA could ameliorate depressive-like behaviors by restoring hippocampus CA1 synaptic plasticity, which might be mainly mediated by regulating 5-HT receptor levels.
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Brain research bulletin · Apr 2018
The opioid epidemic is an historic opportunity to improve both prevention and treatment.
The current narrative describing the national opioid epidemic as the result of overprescribing opioid pain medicines fails to capture the full dimensions of the problem and leads to inadequate and even confounding solutions. Overlooked is the fact that polysubstance use is nearly ubiquitous among overdose deaths, demonstrating that the opioid overdose death problem is bigger than opioids. ⋯ New prevention efforts need to encourage youth to grow to adulthood not using alcohol, nicotine, marijuana or other drugs for reasons of health. New addiction treatment efforts need to focus on achieving long-term recovery including no use of alcohol, marijuana and other drugs.
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Brain research bulletin · Apr 2018
Changes in resting state functional brain connectivity and withdrawal symptoms are associated with acute electronic cigarette use.
Resting state functional brain connectivity (rsFC) may be an important neuromarker of smoking behavior. Prior research has shown, among cigarette smokers, that nicotine administration alters rsFC within frontal and parietal cortices involved in executive control, as well as striatal regions that drive reward processing. These changes in rsFC have been associated with reductions in withdrawal symptom severity. ⋯ Reductions in craving and difficulty with concentration were correlated with decreases in coupling strength between reward and executive control networks. These preliminary results suggest that the effects of ecig use on rsFC are similar to those seen with nicotine administration in other forms. In order to gain insight into the addictive potential of ecigs, further research is needed to understand the neural influence of ecigs across the range of nicotine delivery within this class of products.