Research ReportBi-lateral changes to hippocampal cholesterol levels during epileptogenesis and in chronic epilepsy following focal-onset status epilepticus in mice

Brain cholesterol homeostasis has been shown to be disrupted in neurodegenerative conditions such as Alzheimer's and Huntington's diseases. Investigations in animal models of seizure-induced brain injury suggest that brain cholesterol levels are altered by prolonged seizures (status epilepticus) and are a feature of the pathophysiology of temporal lobe epilepsy. The present study measured hippocampal sterol levels in a model of unilateral hippocampal injury triggered by focal-onset status epilepticus, and in chronically epileptic mice. Status epilepticus was induced by intra-amygdala microinjection of kainic acid and ipsilateral and contralateral hippocampus analyzed. No significant changes were found for ipsilateral or contralateral hippocampal levels of desmosterol or lathosterol at any time after SE as measured by gas chromatography-mass spectrometry. 24S-hydroxycholesterol and cholesterol levels were unchanged up to 24 h after status epilepticus but were decreased in the ipsilateral hippocampus during early epileptogenesis and in chronically epileptic mice. Levels of cholesterol were also reduced in the contralateral hippocampus during epileptogenesis and in chronic epileptic mice. Treatment of mice with the anti-inflammatory cholesterol synthesis inhibitor lovastatin did not alter seizures during status epilepticus or seizure-induced neuronal death. Thus, changes to hippocampal cholesterol homeostasis predominantly begin during epileptogenesis, occur bi-laterally even when the initial precipitating injury is unilateral, and continue into the chronic epileptic period.

► In contrast to what has been published before sterol levels remain unchanged after status epilepticus. ► Sterol levels change during the process of epileptogenesis and are also altered in chronic epileptic mice. ► Cholesterol synthesis inhibitor lovastatin does not provide neuroprotection after status epilepticus. ► Cholesterol levels are decreased during epileptogenesis and in chronic epileptic mice. ► Cholesterol levels are changed bi-laterally even when the initial precipitating injury is unilateral.