Targeting the AKT‐P53/CREB pathway with epicatechin for improved prognosis of traumatic brain injury

Abstract

AimsThe aim of this study was to evaluate the effect of epicatechin, on neurological recovery and neuroinflammation after traumatic brain injury (TBI) to investigate its potential value in clinical practice.MethodsTBI model was established in adult rats by CCI method. The effect of epicatechin was evaluated after intraperitoneal injection. Neurological recovery after TBI was assessed by Morris Water Maze, mNSS score, Rotarod test and Adhesive removal test. Protein and gene expression was assessed by Western blot, ELISA, PCR and immunofluorescence. Furthermore, the use of AKT pathway inhibitors blocked the therapeutic effects of epicatechin clarifying AKT‐P53/CREB as a potential pathway for the effects of epicatechin.ResultsAdministering epicatechin after TBI prevented neuronal death, reduced neuroinflammation, and promoted neurological function restoration in TBI rats. Network pharmacology study suggested that epicatechin may exert its therapeutic benefits through the AKT‐P53/CREB pathwayConclusionThese results indicate that epicatechin, a monomeric compound derived from tea polyphenols, possesses potent antioxidant and anti‐inflammatory properties after TBI. The mechanism may be related to the regulation of the AKT‐P53/CREB signal pathway.

CD300LF+ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

“…As we previously described, 15,16 the TBI model was induced in mice. The mice were anesthetized with isoflurane gas and placed on a stereotaxic apparatus.…”

“…Human samples were taken from contusion brain tissue of patients who underwent hematoma clearance on the first day after TBI, and animal samples were taken from the injured side of the cerebral hemisphere. Brain homogenates were extracted as previously described 15 . After centrifugation, the brain tissue pellet was thoroughly mixed with cell lysis buffer containing a mixture of 1% protease inhibitor and 1% phosphatase inhibitor, and then lysis was promoted by ultrasound.…”

“…Brain homogenates were extracted as previously described. 15 After centrifugation, the brain tissue pellet was thoroughly mixed with cell lysis buffer containing a mixture of 1% protease inhibitor and 1% phosphatase inhibitor, and then lysis was promoted by ultrasound.…”

“…Rotarod test was performed as previously described. 15 Mice were trained on an accelerated (5-30 rpm) rotarod for 3 days. During the test phase, mice were placed on an accelerating rotary rod with the speed increasing from 5 rpm to 30 rpm over 5 min.…”

Ursolic Acid Alleviates Neuroinflammation after Intracerebral Hemorrhage by Mediating Microglial Pyroptosis via the NF-κB/NLRP3/GSDMD Pathway

“…As previously described, neurological function was assessed in each group of rats on days 1, 3, and 7 after cerebral hemorrhage, and mNss scores and corner-turning tests were carried out [43,44].…”