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

• Published in: Brain research Vol. 1480; pp. 81 - 90
• Main Authors: Heverin, Maura, Engel, Tobias, Meaney, Steve, Jimenez-Mateos, Eva M, Al-Saudi, Reza, Henshall, David C
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 22.10.2012; Elsevier
• Subjects: Alzheimer disease; Alzheimer's disease; Animal models; Animals; Biological and medical sciences; Brain; Brain injury; Cholesterol; Cholesterol - metabolism; Chronic epilepsy; death; Epilepsy; Gas chromatography; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - physiopathology; Homeostasis; Huntington's disease; Inflammation; Kainic acid; Kainic Acid - toxicity; Lovastatin; Lovastatin - pharmacology; mass spectrometry; Mass spectroscopy; Medical sciences; Medicin och hälsovetenskap; Mice; Microinjection; Nervous system (semeiology, syndromes); Neurodegenerative diseases; Neurology; Neurons - drug effects; Neurons - metabolism; pathophysiology; Seizure; Seizures; Seizures - chemically induced; Seizures - metabolism; Seizures - physiopathology; Statins; Status Epilepticus - chemically induced; Status Epilepticus - metabolism; Status Epilepticus - physiopathology; Sterols; Temporal lobe; electroencephalographic; Chronic epilepsy; Brain; kainic acid; EEG; Fluoro-Jade B; Cholesterol; TUNEL; KA; Seizure; terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling; Statins; FJB; Kainic acid; Nervous system diseases; Epilepsy; Rodentia; Central nervous system; Lipids; Statin derivative; Cerebral disorder; Encephalon; Vertebrata; Chronic; Mammalia; Convulsion; Mouse; Animal; Central nervous system disease; Neurological disorder; Status epilepticus; Hippocampus
• ISSN: 0006-8993; 1872-6240; 1872-6240
• DOI: 10.1016/j.brainres.2012.08.018

Abstract 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.