RESUMO
It has been reported that the mechanistic target of rapamycin (mTOR) pathway is involved in cerebral ischemia-reperfusion injury. One of the important pathological changes during reperfusion after cerebral ischemia is disruption of blood-brain barrier (BBB). Rapamycin, a first-generation mTOR inhibitor, produces divergent effects on neuronal survival and alteration in BBB disruption. In this study, we investigated how Rapalink-1, a third-generation mTOR inhibitor, would affect neuronal survival and BBB disruption in the very early stage of cerebral ischemia-reperfusion that is within the time window of thrombolysis therapy. The middle cerebral artery occlusion (MCAO) was performed in rats under isoflurane anesthesia with controlled ventilation. Of note, 2 mg/kg of Rapalink-1 or vehicle was administered intraperitoneally 10 min after MCAO. After 1 h of MCAO and 2 h of reperfusion, the transfer coefficient (Ki) of 14C-α-aminoisobutyric acid (104 Da) and the volume of 3H-dextran (70,000 Da) distribution were determined to assess the degree of BBB disruption. At the same time points, phosphorylated S6 (Ser240/244) and Akt (Ser473) as well as matrix metalloproteinase-2 (MMP2) protein level were determined by Western blot along with the infarct size using tetrazolium stain. Rapalink-1 increased the Ki in the ischemic-reperfused cortex (IR-C, +23%, p < 0.05) without a significant change in the volume of dextran distribution. Rapalink-1 increased the percentage of cortical infarct out of the total cortical area (+41%, p < 0.005). Rapalink-1 significantly decreased phosphorylated S6 and Akt to half the level of the control rats in the IR-C, which suggests that both of the mechanistic target of rapamycin complex 1 and 2 (mTORC1 and mTORC2) were inhibited. The MMP2 level was increased suggesting that BBB disruption could be aggravated by Rapalink-1. Taken together, our data suggest that inhibiting both mTORC1 and mTORC2 by Rapalink-1 could worsen the neuronal damage in the early stage of cerebral ischemia-reperfusion and that the aggravation of BBB disruption could be one of the contributing factors.
RESUMO
Epilepsy is a chronic neurological disorder that is increasingly prevalent in developing countries. It is critical to provide appropriate support to patients during seizures in order to prevent injuries. False beliefs regarding the etiology or pathogenesis of the epilepsy and inadequate health information may put patients with epilepsy or other seizure disorders at increased risk of injury. Our objective was to assess the level of epilepsy awareness amongst the general population in Grenada and educate the participants regarding proper first-aid measures. A pilot questionnaire containing a total of 25 items surveying the knowledge, attitudes, and first-aid care of epilepsy was presented to 200 adult residents of Grenada as face-to-face interviews. Study participants were recruited over a nine-month period on a voluntary basis at health fairs, in local communities, and on the campus of St. George's University. Our results indicate that 35 out of 198 (17.7%) respondents erroneously believed that medicine should be placed in a person's mouth during a seizure, and 83 out of 200 (41.5%) answered that a person who is convulsing should be held down. Furthermore, 128 out of 195 (65.6%) respondents erroneously believed that seizures occur when there is low brain activity and an additional 35 out of 199 (17.6%) regarded epilepsy as a contagious disorder. Our data suggest that persons with seizures and/or epilepsy may be at increased risk of injury in Grenada due to common misconceptions and false beliefs. It is critical that epilepsy awareness is promoted in developing countries, such as Grenada, where inadequate health information may be common.