Neuroprotection by a caspase inhibitor in acute bacterial meningitis.
Nat Med
; 5(3): 298-302, 1999 Mar.
Article
em En
| MEDLINE
| ID: mdl-10086385
ABSTRACT
Half of the survivors of bacterial meningitis experience motor deficits, seizures, hearing loss or cognitive impairment, despite adequate bacterial killing by antibiotics. We demonstrate that the broad-spectrum caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone (z-VAD-fmk) prevented hippocampal neuronal cell death and white blood cell influx into the cerebrospinal fluid compartment in experimental pneumococcal meningitis. Hippocampal neuronal death was due to apoptosis derived from the inflammatory response in the cerebrospinal fluid. Apoptosis was induced in vitro in human neurons by inflamed cerebrospinal fluid and was blocked by z-VAD-fmk. As apoptosis drives neuronal loss in pneumococcal meningitis, caspase inhibitors might provide a new therapeutic option directed specifically at reducing brain damage.
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Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
3_ND
/
4_TD
Base de dados:
MEDLINE
Assunto principal:
Infecções Pneumocócicas
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Inibidores de Cisteína Proteinase
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Meningites Bacterianas
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Fármacos Neuroprotetores
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Inibidores de Caspase
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Clorometilcetonas de Aminoácidos
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Nat Med
Ano de publicação:
1999
Tipo de documento:
Article