Disturbances of brain cholesterol metabolism: A new excitotoxic process associated with status epilepticus.
Neurobiol Dis
; 154: 105346, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-33774180
ABSTRACT
The understanding of the excitotoxic processes associated with a severe status epilepticus (SE) is of major importance. Changes of brain cholesterol homeostasis is an emerging candidate for excitotoxicity. We conducted an overall analysis of the cholesterol homeostasis both (i) in fluids and tissues from patients with SE blood (n = 63, n = 87 controls), CSF (n = 32, n = 60 controls), and post-mortem brain tissues (n = 8, n = 8 controls) and (ii) in a mouse model of SE induced by an intrahippocampal injection of kainic acid. 24-hydroxycholesterol levels were decreased in kainic acid mouse hippocampus and in human plasma and post-mortem brain tissues of patients with SE when compared with controls. The decrease of 24-hydroxycholesterol levels was followed by increased cholesterol levels and by an increase of the cholesterol synthesis. Desmosterol levels were higher in human CSF and in mice and human hippocampus after SE. Lanosterol and dihydrolanosterol levels were higher in plasma from SE patients. Our results suggest that a CYP46A1 inhibition could occur after SE and is followed by a brain cholesterol accumulation. The excess of cholesterol is known to be excitotoxic for neuronal cells and may participate to neurological sequelae observed after SE. This study highlights a new pathophysiological pathway involved in SE excitotoxicity.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Estado Epiléptico
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Encéfalo
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Colesterol
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Hidroxicolesteróis
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Neurobiol Dis
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França