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mTOR is involved in stroke-induced seizures and the anti-seizure effect of mild hypothermia
- Source :
- Molecular Medicine Reports
- Publication Year :
- 2018
- Publisher :
- Spandidos Publications, 2018.
-
Abstract
- Stroke is considered an underlying etiology of the development of seizures. Stroke leads to glucose and oxygen deficiency in neurons, resulting in brain dysfunction and injury. Mild hypothermia is a therapeutic strategy to inhibit stroke-induced seizures, which may be associated with the regulation of energy metabolism of the brain. Mammalian target of rapamycin (mTOR) signaling and solute carrier family 2, facilitated glucose transporter member (GLUT)-1 are critical for energy metabolism. Furthermore, mTOR overactivation and GLUT-1 deficiency are associated with genetically acquired seizures. It has been hypothesized that mTOR and GLUT-1 may additionally be involved in seizures elicited by stroke. The present study established global cerebral ischemia (GCI) models of rats. Convulsive seizure behaviors frequently occurred during the first and the second days following GCI, which were accompanied with seizure discharge reflected in the EEG monitor. Expression of phosphor (p)-mTOR and GLUT-1 were upregulated in the cerebral cortex and hippocampus, as evidenced by immunohistochemistry and western blot analyses. Mild hypothermia and/or rapamycin (mTOR inhibitor) treatments reduced the number of epileptic attacks, seizure severity scores and seizure discharges, thereby alleviating seizures induced by GCI. Mild hypothermia and/or rapamycin treatments reduced phosphorylation levels of mTOR and the downstream effecter p70S6 in neurons, and the amount of GLUT-1 in the cytomembrane of neurons. The present study revealed that mTOR is involved in stroke-induced seizures and the anti-seizure effect of mild hypothermia. The role of GLUT-1 in stroke-elicited seizures appears to be different from the role in seizures induced by other reasons. Further studies are necessary in order to elucidate the exact function of GLUT-1 in stroke-elicited seizures.
- Subjects :
- Male
0301 basic medicine
Cancer Research
Ischemia
Hippocampus
Pharmacology
Electroencephalography
Severity of Illness Index
Biochemistry
Brain Ischemia
03 medical and health sciences
0302 clinical medicine
Hypothermia, Induced
Seizures
mild hypothermia
Genetics
Animals
Medicine
Molecular Biology
Stroke
PI3K/AKT/mTOR pathway
mammalian target of rapamycin
Neurons
Sirolimus
Glucose Transporter Type 1
medicine.diagnostic_test
business.industry
TOR Serine-Threonine Kinases
solute carrier family 2 facilitated glucose transporter member 1
Glucose transporter
Articles
Hypothermia
medicine.disease
Immunohistochemistry
stroke
Rats
Disease Models, Animal
Glucose
030104 developmental biology
medicine.anatomical_structure
Oncology
Cerebral cortex
Molecular Medicine
medicine.symptom
business
Biomarkers
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 17913004 and 17912997
- Database :
- OpenAIRE
- Journal :
- Molecular Medicine Reports
- Accession number :
- edsair.doi.dedup.....62cc48f488a29a057ee68aa0934cc45e