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Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins
Published on: August 15, 2017
Effect of mild hypothermia on glutamate receptor expression after status epilepticus
Lifei Yu1, Yuanfeng Zhou, Yi Wang
1Department of Neurology, Children's Hospital of Fudan University, 399 Wanyuan Road, Minhang District, Shanghai, China. Yulifei7711@163.com
Insights
Mild hypothermia combined with diazepam offers neuroprotection in pediatric status epilepticus (SE) models. This combination therapy significantly reduces seizure activity and cell death by modulating glutamate receptor expression in immature rats.
Area of Science:
- Neuroscience
- Pediatric Neurology
- Critical Care Medicine
Background:
- Hypothermia demonstrates neuroprotective effects in various neurological damage models.
- The therapeutic efficacy of hypothermia in pediatric status epilepticus (SE) remains largely unexplored.
Purpose of the Study:
- To investigate the adjuvant effect of mild hypothermia on diazepam treatment for pilocarpine-induced status epilepticus in immature rats.
- To assess the impact of hypothermia on seizure activity, neuronal cell death, and glutamate receptor expression in a pediatric SE model.
Main Methods:
- Immature rats underwent pilocarpine-induced status epilepticus (SE) for 30 or 60 minutes.
- Animals received diazepam (10mg/kg) and/or mild hypothermia (core temperature to 33°C).
- EEG, cell death markers (necrosis, apoptosis), and glutamate receptor subunit expression (GluR1, GluR2, mGluR-1a) were analyzed.
Main Results:
- Combined diazepam and hypothermia treatment significantly reduced spike-wave amplitude and frequency compared to diazepam alone.
- Mild hypothermia markedly decreased neuronal necrosis and apoptosis.
- Combination therapy modulated glutamate receptor expression, decreasing GluR1 and increasing GluR2 and mGluR-1a compared to diazepam alone.
Conclusions:
- Mild hypothermia acts as an adjuvant therapy to diazepam, providing enhanced neuroprotection in a pediatric model of status epilepticus.
- The protective effects are associated with reduced neuronal cell death and regulation of glutamate receptor expression, particularly AMPA and mGluR subunits.
- Findings suggest potential therapeutic benefits of hypothermia in managing pediatric SE, especially in the developing brain.
Abstract:
Hypothermia has been shown to have neuroprotective effects in various models of neurological damage. However, its therapeutic effect on pediatric status epilepticus (SE) is still unknown. We conducted a study to investigate whether hypothermia can have an adjuvant effect on pilocarpine-induced status epilepticus in immature rats when combined with diazepam treatment. Pilocarpine-induced status epilepticus was maintained for either 30 min or 60 min, which was followed by injection with diazepam (10mg/kg body weight) and/or treatment with mild hypothermia (core temperature to 33°C). We found that the spike-wave amplitude and frequency after SE during treatment with diazepam and hypothermia was significantly lower than treatment with diazepam alone. Mild hypothermia significantly reduced the number of cells undergoing necrosis and apoptosis. In addition, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor subunit GluR1 was shown to be up-regulated by SE, while GluR2 was shown to be down-regulated. However, after combination therapy with diazepam and mild hypothermia for 8h, the expression of GluR1 was decreased and GluR2 was increased relative to the levels of diazepam alone treated juveniles. We also found that the expression of mGluR-1a was also decreased relative to diazepam alone. These findings suggest that mild hypothermia might further protect against pilocarpine-induced status epilepticus in immature rats by regulating glutamate receptor expression. This study was conducted using a pediatric model of SE so as to gain a better understanding of the role of hypothermia in the developing brain.
