Brain research
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JM-1232(-) (JM) is a novel isoindoline derivative with sedative and hypnotic activities that are mediated by binding to the benzodiazepine site of the Gamma-aminobutyric acid type A (GABAA) receptor. Although the neuroprotective effects of other GABAA receptor agonists are well known, there is no published report regarding JM. Thus, we examined the effects of JM on neurons exposed to oxygen-glucose deprivation (OGD) using rat hippocampal slice cultures. ⋯ To analyze more immediate effects of JM, we next measured the fluorescence of Oregon Green 488 BAPTA-1 during the OGD and re-oxygenation periods, and evaluated changes in intracellular Ca(2+) in single CA1 pyramidal neurons. JM reduced the elevation of intracellular Ca(2+) concentration during OGD, and this effect was antagonized by flumazenil. These findings indicate that JM suppressed the elevation of intracellular Ca(2+) concentration during OGD through GABAA receptors, but its neuroprotective effects from necrotic changes also involve other unknown mechanisms.
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We have previously shown that acute intravenous (i.v.) administration of cocaine increases Fos immunoreactivity in rats under isoflurane anesthesia. Given that Fos expression is a marker of neural activation, the results suggested that isoflurane is appropriate for imaging cocaine effects under anesthesia. However, most imaging research in this area utilizes subjects with a history of repeated cocaine exposure and this drug history may interact with anesthetic use differently from acute cocaine exposure. ⋯ We found that challenge injections of cocaine following a regimen of repeated cocaine exposure resulted in Fos expression in the prefrontal cortex and striatum roughly equivalent to that found in rats who had received the cocaine challenge after a history of vehicle injections. Additionally, isoflurane anesthesia resulted in a heterogeneous attenuation of cocaine-induced Fos expression, with the most robust effect in the orbital cortex but no effect in the nucleus accumbens core (NAcC). These results indicate that cocaine-induced Fos is preserved in the NAcC under isoflurane, suggesting that isoflurane can be used in imaging studies involving cocaine effects in this region.
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Previous studies have demonstrated that the commonly used anesthetic ketamine can induce widespread neuroapoptosis in the neonatal brain and can cause persistent cognitive impairments as the animal matures. Therefore, searching for adjunctive neuroprotective strategies that inhibit ketamine-induced neuroapoptosis and persistent cognitive impairments is highly warranted. The primary goal of this study was to investigate the protective effect of 17β-estradiol against ketamine-induced neuroapoptosis and persistent cognitive impairments in adult rats. ⋯ Moreover, 17β-estradiol significantly reversed the learning and memory deficits observed at 60 days of age. In brief, our present data demonstrate that 17β-estradiol attenuates ketamine-induced neuroapoptosis and reverses long-term cognitive deficits in developing rats and thus may be a potential therapeutic and neuroprotective method for the treatment of neurodevelopmental disorders. This article is part of a Special Issue entitled SI: Brain and Memory.
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Cerebral aneurysm (CA) rupture is a major cause of subarachnoid hemorrhage with high morbidity and mortality. Using an animal model, we examined the potential of endothelial colony-forming cells (ECFCs) transfusion on vascular degeneration after CA induction and underlying mechanisms. CA was induced in the right anterior cerebral artery-olfactory artery (ACA/OA) bifurcations in Sprague-Dawley rats with or without ECFCs transfusion. ⋯ ECFCs transfusion dramatically decreased VCAM-1 and NF-κB expression, increased eNOS expression and caused no change in MCP-1 expression, which was accompanied by reduced macrophages infiltration. Moreover, ECFCs transfusion reversed downregulation of Bcl-2 expression and upregulation of iNOS expression, and decreased SMCs apoptosis. Collectively, these findings suggest that ECFCs transfusion confers protection against degeneration of aneurysmal wall by inhibiting inflammatory cascades and SMCs apoptosis.
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The aim of this study is to explore the white matter structure integrity in patients with mild traumatic brain injury (mTBI) using diffusion tensor imaging (DTI), and to analyze the relationship between the white matter structure integrity and cognitive impairment of patients with mTBI. Twenty-five patients with mTBI and 25 healthy control subjects were studied with conventional MR imaging and diffusion tensor imaging. Fractional anisotropy (FA) and mean diffusivity (MD) maps of patients with mTBI were calculated and compared, with these control maps using tract-based spatial statistics (TBSS). ⋯ There was a positive correlation between the FA value of the uncinate fasciculus and Mini Mental State Examination (MMSE) in the mTBI patient group (R(2)=0.36, P<0.05). TBSS analysis of DTI suggests that patients with mTBI have focal axonal injury, and the pathophysiology is significantly related to the MMSE and IQ of mTBI patients. Diffusion tensor imaging can be a powerful technique for in vivo detection of mTBI, and can help in the diagnosis of patients with mTBI.