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Upregulation of serum and glucocorticoid-regulated kinase 1 exacerbates brain injury and neurological deficits after cardiac arrest.
Lee, Reggie Hui-Chao; Grames, Mychal S; Wu, Celeste Yin-Chieh; Lien, Chih-Feng; Couto E Silva, Alexandre; Possoit, HarLee E; Clemons, Garrett A; Citadin, Cristiane T; Neumann, Jake T; Pastore, Donatella; Lauro, Davide; Della-Morte, David; Lin, Hung Wen.
Afiliación
  • Lee RH; Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
  • Grames MS; Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
  • Wu CY; Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
  • Lien CF; Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
  • Couto E Silva A; Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
  • Possoit HE; Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
  • Clemons GA; Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
  • Citadin CT; Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
  • Neumann JT; Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
  • Pastore D; Department of Biomedical Sciences, West Virginia School of Osteopathic Medicine, Lewisburg, West Virginia.
  • Lauro D; Department of Systems Medicine, University of Rome Tor Vergata, Rome. Italy.
  • Della-Morte D; Department of Systems Medicine, University of Rome Tor Vergata, Rome. Italy.
  • Lin HW; Department of Systems Medicine, University of Rome Tor Vergata, Rome. Italy.
Am J Physiol Heart Circ Physiol ; 319(5): H1044-H1050, 2020 11 01.
Article en En | MEDLINE | ID: mdl-32946263
Cardiopulmonary arrest (CA) is the leading cause of death and disability in the United States. CA-induced brain injury is influenced by multifactorial processes, including reduced cerebral blood flow (hypoperfusion) and neuroinflammation, which can lead to neuronal cell death and functional deficits. We have identified serum and glucocorticoid-regulated kinase-1 (SGK1) as a new target in brain ischemia previously described in the heart, liver, and kidneys (i.e., diabetes and hypertension). Our data suggest brain SGK1 mRNA and protein expression (i.e., hippocampus), presented with hypoperfusion (low cerebral blood flow) and neuroinflammation, leading to further studies of the potential role of SGK1 in CA-induced brain injury. We used a 6-min asphyxia cardiac arrest (ACA) rat model to induce global cerebral ischemia. Modulation of SGK1 was implemented via GSK650394, a SGK1-specific inhibitor (1.2 µg/kg icv). Accordingly, treatment with GSK650394 attenuated cortical hypoperfusion and neuroinflammation (via Iba1 expression) after ACA, whereas neuronal survival was enhanced in the CA1 region of the hippocampus. Learning/memory deficits were observed 3 days after ACA but ameliorated with GSK650394. In conclusion, SGK1 is a major contributor to ACA-induced brain injury and neurological deficits, while inhibition of SGK1 with GSK650394 provided neuroprotection against CA-induced hypoperfusion, neuroinflammation, neuronal cell death, and learning/memory deficits. Our studies could lead to a novel, therapeutic target for alleviating brain injury following cerebral ischemia.NEW & NOTEWORTHY Upregulation of SGK1 exacerbates brain injury during cerebral ischemia. Inhibition of SGK1 affords neuroprotection against cardiac arrest-induced hypoperfusion, neuroinflammation, neuronal cell death, and neurological deficits.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesiones Encefálicas / Proteínas Serina-Treonina Quinasas / Proteínas Inmediatas-Precoces / Paro Cardíaco / Memoria Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Am J Physiol Heart Circ Physiol Asunto de la revista: CARDIOLOGIA / FISIOLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesiones Encefálicas / Proteínas Serina-Treonina Quinasas / Proteínas Inmediatas-Precoces / Paro Cardíaco / Memoria Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Am J Physiol Heart Circ Physiol Asunto de la revista: CARDIOLOGIA / FISIOLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos