Inhibition of the pSPAK/pNKCC1 signaling pathway protects the bloodbrain barrier and reduces neuronal apoptosis in a rat model of surgical brain injury.
Mol Med Rep
; 24(4)2021 10.
Article
em En
| MEDLINE
| ID: mdl-34396440
ABSTRACT
Surgical brain injury (SBI) can disrupt the function of the bloodbrain barrier (BBB), leading to brain edema and neurological dysfunction. Thus, protecting the BBB and mitigating cerebral edema are key factors in improving the neurological function and prognosis of patients with SBI. The inhibition of WNK lysine deficient protein kinase/STE20/SPS1related proline/alaninerich kinase (SPAK) signaling ameliorates cerebral edema, and this signaling pathway regulates the phosphorylation of the downstream Na+K+Cl cotransporter 1 (NKCC1). Therefore, the purpose of the present study was to investigate the role of SPAK in SBIinduced cerebral edema and to determine whether the SPAK/NKCC1 signaling pathway was involved in SBI via regulating phosphorylation. An SBI model was established in male SpragueDawley rats, and the effects of SPAK on the regulation of the NKCC1 signaling pathway on BBB permeability and nerve cell apoptosis by western blotting analysis, immunofluorescence staining, TUNEL staining, FluoroJade C staining, and brain edema and nervous system scores. The results demonstrated that, compared with those in the sham group, phosphorylated (p)SPAK and pNKCC1 protein expression levels were significantly increased in the SBI model group. After inhibiting pSPAK, the expression level of pNKCC1, neuronal apoptosis and BBB permeability were significantly reduced in SBI model rats. Taken together, these findings suggested that SBIinduced increases in pSPAK and pNKCC1 expression exacerbated posttraumatic neural and BBB damage, which may be mediated via the iontransportinduced regulation of cell edema.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Encefálicas
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Barreira Hematoencefálica
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Transdução de Sinais
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Proteínas Serina-Treonina Quinases
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Apoptose
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Substâncias Protetoras
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Membro 2 da Família 12 de Carreador de Soluto
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2021
Tipo de documento:
Article