Brain research
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Male animals exhibit greater neuronal damage following focal cerebral ischemic injury in many experimental injury models, however the mechanism of this is unknown. This study used cardiac arrest and cardiopulmonary resuscitation (CA/CPR) in male mice exposed to physiological vs. pharmacological doses of testosterone and tested the hypothesis that testosterone increases damage following global cerebral ischemia. Analysis of histological damage 72h after resuscitation revealed a complex dose-response curve for testosterone, such that low and high doses of testosterone exacerbated ischemic neuronal damage, while intermediate doses had no effect on neuronal survival. ⋯ Finally, the androgen receptor antagonist flutamide inhibited the increase in neuronal damage and sensorimotor impairment observed in testosterone treated mice. Our data showed that low and supra-physiological levels of testosterone increase neuronal damage following global cerebral ischemia and that blockade of androgen receptors limits this injury. Therefore, this study indicated that testosterone may have a role in determining sex-linked differences in cerebrovascular disease as well as having important health implications in clinical conditions of elevated testosterone.
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Thalidomide, a derivative of glutamic acid, is used for immunomodulatory therapy in various diseases through inhibition of tumor necrotic factor-α (TNF-α) release. However, the effects of thalidomide in central nervous system (CNS) diseases such as stroke or hypoxic-ischemic encephalopathy (HIE) are unknown. In this study, we aimed to test whether thalidomide protects against hypoxic-ischemic neuronal damage and the possible signaling pathway involved in neuroprotection. ⋯ Meanwhile, we found that thalidomide induced p-Akt expression, which could be inhibited by PI3K specific inhibitor, LY294002. In addition, inhibition of PI3K increased CC3 but decreased Bcl-2 expression. In summary, thalidomide has anti-apoptotic effects on cortical neurons after OGD by modulating CC3 and Bcl-2 expression through activation of PI3K/Akt pathway.
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Emerging evidence has demonstrated that postconditioning with sevoflurane provided neuroprotection. In this study, we investigated the neuroprotective effect of different concentrations of sevoflurane in rats with middle cerebral artery occlusion (MCAO). Furthermore, we tested the hypothesis that the neuroprotective effect of postconditioning with sevoflurane is associated with inhibition of apoptosis and mediated by activation of the phosphoinositide-3-kinase/Akt (PI3K/Akt) pathway. ⋯ Wortmannin abolished the neuroprotective effect and prevented the increasing of p-Akt. Our data suggest postconditioning with sevoflurane (1.0 MAC and 1.5 MAC) not only reduced infarct volume but also improved learning and memory. Our study further showed that this neuroprotective effect may be partly due to the activation of PI3K/Akt pathway and inhibiting neuronal apoptosis.
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In recent years misuse of methylphenidate (MPH) has been reported. The main pharmacological target of methylphenidate is the dopaminergic system. Adenosine is a neuromodulator that influences the dopaminergic neurotransmission, but studies on MPH and adenosine are still lacking. ⋯ Our findings ruled out the participation of adenosine A(1) receptors on the MPH-triggered anxiolytic effects. However, the density of adenosine A(1) receptors increased in a brain area strictly involved in the MPH-mediated effects. Thus, the adenosinergic system may play a role in the methylphenidate actions in the central nervous system.
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Transient cerebral ischemia may result in neuronal apoptosis. During this process, several apoptosis-regulatory genes are induced in apoptotic cells. Among these genes, cysteinyl aspartate-specific protease-3 (caspase-3) and B-cell leukemia-2 (Bcl-2) are the most effective apoptotic regulators because they play a decisive role in the occurrence of apoptosis. ⋯ In the propofol (1.0mg/kg) intervention group, the hippocampal expression of caspase-3 mRNA decreased significantly in rats 24h after ischemia; Bcl-2 mRNA was increased at the same time point. During the 24-h reperfusion period and after treatment with propofol, the level of caspase-3 protein expression was low, while the level of Bcl-2 was high. Thus, our results suggest that the neuroprotective effects of propofol against neuronal apoptosis may be mediated by the inhibition of caspase-3 expression and an increase in Bcl-2 expression.