Everolimus inhibits PI3K/Akt/mTOR and NF-kB/IL-6 signaling and protects seizure-induced brain injury in rats.

BACKGROUND: Epilepsy is a common chronic neurological disease caused by the over-synchronization of neurons leading to brain dysfunction. Recurrent seizures can lead to cognitive and behavioral deficits, and irreversible brain damage. While the PI3K/Akt/mTOR pathway regulates various physiological processes of neurons and glia, it may also lead to abnormal neuronal signal transduction under pathological conditions, including that of epilepsy. Everolimus (Eve), an mTOR inhibitor, may modulate neuronal excitability and therefore exert protection against epilepsy. Therefore, this study aimed to investigate the neuroprotective effect of Everolimus on seizure-induced brain injury and its regulation of the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway. Kainic acid (KA) 15 mg/kg was used to induce seizures and Everolimus (1, 2, 5 mg/kg) was administered as a pretreatment. Hippocampal tissue was extracted 24 h post-seizure. RESULTS: The protein and mRNA expression levels of PI3K、p-AKt、p-mTOR、NF-kB and IL-6 as well as neuronal apoptosis and microglia activation, significantly increased after KA-induced seizures, however, these effects were inhibited by Everolimus treatment. Furthermore, pretreatment with Everolimus decreased seizure scores and increased seizure latency. CONCLUSIONS: Everolimus can decrease the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway, reduce neuronal apoptosis and microglia activation, and attenuate seizure susceptibility and intensity, thus having a protective effect on seizure-induced brain damage.

Effect of ischemic pretreatment on expression of heat shock protein 70 and injury of spinal cord in canine / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate effect of ischemic pretreatment on expression of heat shock protein 70 (HSP70) and injury of spinal cord in canine.</p><p><b>METHODS</b>Fourty-one canine were divided into three groups: the sham-operative group, the pretreatment group and the control group. In the pretreatment group aorta was obstructed for 6 min, and then was opened for 6 min, this procedure was repeated twice, finally aorta was obstructed for 35 min. In the control group aorta was obstructed for 35 min. Nervous function were assessed and HSP70 expression were detected in tissue of spinal cord.</p><p><b>RESULTS</b>In the pretreatment group, HSP70 expressed in cytoplasm and nucleus at 6, 24 hour after reperfusion, and intensity of HSP70 expression was stronger than that in the control group; The score of nervous function in the pretreatment group was higher than that in the control group. On 7 day after reperfusion the score of nervous function in pretreatment group had no obvious variation, and HSP70 expression was still observed.</p><p><b>CONCLUSIONS</b>Ischemic pretreatment can improve ischemic tolerance of spinal cord; HSP70 expression in cytoplasm and nucleus may play a role in ischemic tolerance.</p>