The action of thrombin in intracerebral hemorrhage induced brain damage is mediated via PKCα/PKCδ signaling

The present study investigates the role of protein kinase C alpha/delta (PKCα/PKCδ) in brain injury induced by intracerebral hemorrhage (ICH) by utilizing a rat model that received intracerebral injections of autologous blood and thrombin (TM). The activation and expression of PKC and PKCδ were analyzed by Western blot and immunohistochemistry. A PKC inhibitor, dihydrochloride (H7), was administrated intraperitoneally after injury to evaluate the effect of inhibition of PKC on ICH and TM induced brain damage. Our data indicate that both ICH and TM increased the expression of PKCα/PKCδ in the brain tissue, and PKCα expression peaked at 6 h, while PKCδ expression reached its maximum value at 72 h post-injury. Administration of H7 significantly reduced the inflammatory cells infiltrate, permeability of brain–blood barrier (BBB), brain edema, and neuronal death. We conclude that both PKCα and PKCδ play important roles in ICH and TM-induced brain injury, and dihydrochloride (H7) can attenuate brain damage after ICH.

Research Highlights
► H7 reduced the inflammatory cell infiltration and the apoptosis cells in ICH and TM.
► H7 reduced the inflammatory cell infiltration and the apoptosis cells.
► TM and autologous blood increased the expression of PKCa/PKCδ protein in rat brain.
► H7 reduced the expression of PKCa/PKCδ protein induced by ICH and TM.