Inhibiting of RIPK3 attenuates early brain injury following subarachnoid hemorrhage: Possibly through alleviating necroptosis - 20/09/18
páginas | 8 |
Iconografías | 6 |
Vídeos | 0 |
Otros | 0 |
Graphical abstract |
Highlights |
• | RIPK3-mediated necroptosis is involved in the early stage of SAH pathology. |
• | RIPK3 inhibitor GSK’872 could alleviate early brain injury following SAH. |
• | GSK’872 could inhibit neuronal necroptosis after SAH. |
• | GSK’872 could inhibit the translocation of HMGB1 to cytoplasm after SAH. |
Abstract |
Necroptosis is an inflammatory form of cell death that depends on receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) and displays the morphological characteristics of necrosis. To date, it is unclear to what extent necroptosis contributes to subarachnoid hemorrhage (SAH) induced brain injury. The present study aimed to investigate the RIPK3-mediated necroptosis and the effects of the RIPK3 selective inhibitor GSK’872 in early brain injury following SAH. After SAH, RIPK3 expression increased as early as 6 h and peaked at 72 h. Double immunofluorescence staining revealed that RIPK3 was mainly located in neurons. Most necrotic cells were neurons, which were further confirmed by TEM. Intracerebroventricular injection of GSK’872 (25 mM) could attenuate brain edema and improve neurological function following SAH and reduce the number of necrotic cells. In addition, GSK’872 could also decrease the protein levels of RIPK3 and MLKL, and cytoplasmic translocation and expression of HMGB1, an important pro-inflammatory protein. Taken together, the current study provides the new evidence that RIPK3-mediated necroptosis is involved in early brain injury and GSK’872 decreases the RIPK3-mediated necroptosis and subsequent cytoplasmic translocation and expression of HMGB1, as well as ameliorates brain edema and neurological deficits.
El texto completo de este artículo está disponible en PDF.Keywords : Subarachnoid hemorrhage, Early brain injury, RIPK3, Necroptosis, GSK’872
Esquema
Vol 107
P. 563-570 - novembre 2018 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
El acceso al texto completo de este artículo requiere una suscripción.
Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
La compra de artículos no está disponible en este momento.
¿Ya suscrito a @@106933@@ revista ?