Alpha lipoic acid inhibits oxidative stress-induced apoptosis by modulating of Nrf2 signalling pathway after traumatic brain injury.

Alpha lipoic acid (ALA) is a powerful antioxidant which has been widely used in the treatment of different system diseases, such as cardiovascular and cerebrovascular diseases. But, there are few studies that refer to protective effects and potential mechanisms on traumatic brain injury (TBI). This study was carried out to investigate the neuroprotective effect following TBI and illuminate the underlying mechanism. Weight drop-injured model in rats was induced by weight-drop. ALA was administrated via intraperitoneal injection after TBI. Neurologic scores were examined following several tests. Neurological score was performed to measure behavioural outcomes. Nissl staining and TUNEL were performed to evaluate the neuronal apoptosis. Western blotting was engaged to analyse the protein content of the Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream protein factors, including hemeoxygenase-1 (HO-1) and quinine oxidoreductase-1 (NQO1). ALA treatment alleviated TBI-induced neuron cell apoptosis and improved neurobehavioural function by up-regulation of Nrf2 expression and its downstream protein factors after TBI. This study presents new perspective of the mechanisms responsible for the neuronal apoptosis of ALA, with possible involvement of Nrf2 pathway.

Rutin Acid Ameliorates Neural Apoptosis Induced by Traumatic Brain Injury via Mitochondrial Pathways in Mice.

Rutin reportedly conveys many beneficial effects, including neuroprotection in brain injury. However, the mechanisms underlying these effects are still not well understood. This study investigates the effect of rutin on potential mechanisms for neuroprotective effects, using the weight-drop model of traumatic brain injury (TBI) in male mice treated either with rutin or a vehicle via intraperitoneal injection 30 min after TBI. After euthanasia and 24 h after TBI, all mice were examined by tests, including neurologic scores, blood-brain barrier permeability, brain water content and neuronal cell death in the cerebral cortex. Results indicate that the levels of cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD) were restored by rutin treatment. Rutin treatment resulted in the downregulation of caspase-3 expression in a reduced number of positive cells under terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and also the improved survival of neurons. Furthermore, pretreatment levels of MDA were restored, while Bcl-2-associated X protein translocation to mitochondria and cytochrome c release into cytosol were reduced by rutin treatment. Our results demonstrate that rutin improves neurological outcome by protecting neural cells against apoptosis via mechanisms that involve the mitochondria following TBI.

The safety and efficacy of levetiracetam versus phenytoin for seizure prophylaxis after traumatic brain injury: A systematic review and meta-analysis.

BACKGROUND: The standard for early traumatic brain injury (TBI) seizure prophylaxis is phenytoin (PHT). Levetiracetam (LEV) has been proposed as an alternative to PHT. The aim of this study was to evaluate the safety and efficacy of LEV on TBI seizure when compared with PHT. METHODS: A search was carried out based on the databases from Pubmed, Embase and the Cochrane database up to May 2015. The relative risk (RR) and the relevant 95% confidence intervals (CI) were determined. RESULTS: Eight observational studies and one randomized controlled trial involving 2035 cases were included. The results indicated that no significant differences in terms of overall seizure (RR = 0.90; 95% CI = 0.51-1.53; p = 0.68), early seizure (RR = 1.06; 95% CI = 0.37-3.07; p = 0.92) and late seizure (RR = 1.10; 95% CI = 0.43-2.79; p = 0.85) occurrence. However, LEV was associated with a lower adverse drug reaction rate (RR = 0.43; 95% CI = 0.23-0.81; p = 0.01). Moreover, there were no significant differences in terms of mortality, length of ICU or hospital stay between groups. CONCLUSIONS: The meta-analysis suggests that LEV appears to have a similar efficacy to PHT on TBI. A better safety profile of LEV is supported by this analysis.

Specific knockdown of hippocampal astroglial EphB2 improves synaptic function via inhibition of D-serine secretion in APP/PS1 mice.

Increasing evidence emphasizes the protective role of Eph receptors in synaptic function in the pathological development of Alzheimer's disease (AD); however, their roles in the regulation of hippocampal astrocytes remain largely unknown. Here, we directly investigated the function of astroglial EphB2 on synaptic plasticity in APP/PS1 mice. Using cell isolation and transgene technologies, we first isolated hippocampal astrocytes and evaluated the expression levels of ephrinB ligands and EphB receptors. Then, we stereotaxically injected EphB2-Flox-AAV into the hippocampus of GFAP-cre/APP/PS1 mice and further evaluated hippocampal synaptic plasticity and astroglial function. Interestingly, astrocytic EphB2 expression was significantly increased in APP/PS1 mice in contrast to its expression profile in neurons. Moreover, depressing this astroglial EphB2 upregulation enhanced hippocampal synaptic plasticity, which results from harmful D-serine release. These results provide evidence of the different expression profiles and function of EphB2 between astrocytes and neurons in AD pathology.

Sinomenine reduces neuronal cell apoptosis in mice after traumatic brain injury via its effect on mitochondrial pathway.

BACKGROUND: Sinomenine (SIN) has been shown to have protective effects against brain damage following traumatic brain injury (TBI). However, the mechanisms and its role in these effects remain unclear. This study was conducted to investigate the potential mechanisms of the protective effects of SIN. METHODS: The weight-drop model of TBI in Institute of Cancer Research (ICR) mice were treated with SIN or a vehicle via intraperitoneal administration 30 min after TBI. All mice were euthanized 24 h after TBI and after neurological scoring, a series of tests were performed, including brain water content and neuronal cell death in the cerebral cortex. RESULTS: The level of cytochrome c (Cyt c), malondialdehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase 1 (SOD) were restored to some degree following the SIN treatment. The SIN treatment significantly decreased caspase-3 expression and reduced the number of positive cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and improved the survival of neuronal cells. Additionally, the pretreatment levels of MDA were restored, while Bax translocation to mitochondria and Cyt c release into the cytosol were reduced by the SIN treatment. CONCLUSION: SIN protected neuronal cells by protecting them against apoptosis via mechanisms that involve the mitochondria following TBI.