FERM domain containing kindlin 1 knockdown attenuates inflammation induced by intracerebral hemorrhage in rats via NLR family pyrin domain containing 3/nuclear factor kappa B pathway

Abstract

Intracerebral hemorrhage (ICH) is an incurable neurological disease. Microglia activation and its related inflammation contribute to ICH-associated brain damage. FERM domain containing kindlin 1 (FERMT1) is an integrin-binding protein that participates in microglia-associated inflammation, but its role in ICH is unclear. An ICH model was constructed by injecting 50 μl of autologous blood into the bregma of rats. FERMT1 siRNA was injected into the right ventricle of the rat for knockdown of FERMT1. A significant striatal hematoma was observed in ICH rats. FERMT1 knockdown reduced the water content of brain tissue, alleviated brain hematoma and improved behavioral function in ICH rats. FERMT1 knockdown reduced microglia activity, inhibited NLR family pyrin domain containing 3 (NLRP3) inflammasome activity and decreased the expression of inflammatory factors including interleukin-1β (IL-1β) and interleukin 18 (IL-18) in the peri-hematoma tissues. BV2 microglial cells were transfected with FERMT1 siRNA and incubated with 60 μM Hemin for 24 h. Activation of NLRP3 inflammasome induced by hemin were reduced in microglia when FERMT1 was knocked down, leading to decreased production of inflammatory factors IL-1β and IL-18. In addition, knockdown of FERMT1 prevented the activation of nuclear factor kappa B (NF-κB) signaling pathway in vivo and in vitro. Our findings suggested that down-regulation of FERMT1 attenuated microglial inflammation and brain damage induced by ICH via NLRP3/NF-κB pathway. FERMT1 is a key regulator of inflammatory damage in rats after ICH.

Jingfang granules protects against intracerebral hemorrhage by inhibiting neuroinflammation and protecting blood-brain barrier damage

“…Rats were anaesthetized using isoflurane and secured to a rat stereotaxic apparatus for experimentation. A burr hole with a diameter of 1 mm was created at the given coordinates in relation to the bregma: 0.2 mm anterior, 3.5 mm left lateral, 6 mm deep [ 32 ]. Subsequently, a 1 μl micro syringe (Gaoge, Shanghai, China) was employed to introduce 1μl saline with 0.2 U collagenase IV (C8160, Solarbio, Beijing, China) at a speed of 0.1 μl/min for a duration of 10 minutes.…”