Activation of PDGFR and ROS in early brain injury in rats after subarachnoid hemorrhage

Objective To investigate the effects of inhibiting the activation of platelet-derived growth factor receptor (PDGFR) and reactive oxygen species (ROS) on early brain damage (EBI) after subarachnoid hemorrhage (SAH), and explore their possible acting mechanism in the process. Methods Adult male SD rats were randomly divided into sham operation group, SAH group, PDGF receptor inhibition group and ROS inhibition group, with 12 rats in each group. The rat model of SAH was established by intravascular puncture. In 1 h later, the rats in the treatment groups were injected with corresponding drugs by intraperitoneal injection. At 24 and 48 h after operation, animal mortality and body weight changes were observed, brain dysfunction was evaluated with neurobehavioral assessment, and brain water content was measured to evaluate blood-brain barrier permeability. Western blot analysis was used to detect the changes of PDGFR and phosphorylated PDGFR and the expression of p-JNK and p-MMP-9 after SAH. The oxidation products of lipids and proteins, malondialdehyde (MDA) and ROS were also detected. Results Both inhibiting the activation of PDGFR and scavenging ROS reduced brain water content after SAH (P < 0.05), decreased the expression of MMP-9 (P < 0.05), improved the neurological function score (P < 0.05), reduced the production of ROS and MDA (P < 0.05), and decreased the phosphorylation of JNK and c-Jun. Inhibiting the generation of ROS suppressed the activation of PDGFR to a certain extent, and inhibiting the activation of PDGFR also reduced the generation of ROS to a certain extent (P < 0.05). Conclusion After SAH in rats, ROS is involved in the activation of PDGFR, and its activation can further aggravate free radical damage. The JNK-MMP-9 pathway is indeed an important pathway that causes blood-brain barrier disruption in EBI.