Neuroprotective effect of breviscapine in rats with traumatic brain injury

  Objective  To explore neuroprotective effect of breviscapine (Bre) and its mechanism in rats with traumatic brain injury (TBI).

  Methods  TBI model was established in specific pathogen free Wistar rats and the rats were divided into 6 groups (24 in each group):a sham operation group and a TBI model group with saline, three dose groups with low, moderate and high Bre (6, 12 and 24 mg/kg), and a citicoline sodium (100 mg/kg) group; all the treatments were administered intragastrically once a day continuously for 5 days. Neurological severity score (NSS) was used to evaluate the neurological function of the rats at 5th day of the treatments. Water content of brain tissues and the permeability of blood-brain barrier were determined and brain tissue samples were collected for all the rats by the end of the treatments. The levels of S100B protein (S100B), neuron-specific enolase (NSE), tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), interleukin-18 (IL-18) and interleukin-6 (IL-6) were measured with enzyme-linked immunosorbent assay (ELISA); the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS) were detected with kit assay; and the levels of NOD-like receptor protein 3 (NLRP3) and caspase-1 were detected with Western blot.

  Results  Compared with those in the rats with sham operation, the NSS score, brain water content, content of evansblue (EB), and levels of MDA, S100B, NSE, TNF-α, IL-1β, IL-8, IL-6, ROS, NLRP3, caspase-1 increased significantly (all P < 0.05) but the level of SOD decreased significantly (P < 0.05) in the TBI model rats. The pyramidal cells with scattered arrangement, shrunken cell bodies and indistinct nucleoli were observed in hippocampal regions of TBI model rats. In comparison with those in the TBI model rats, the NSS score, brain water content, content of EB and levels of MDA, S100B, NSE, TNF-α, IL-1β, IL-8, IL-6, ROS, NLRP3, and caspase-1 decreased significantly (all P < 0.05) but the level of SOD increased significantly (P < 0.05) in the TBI model rats with Bre treatments; the pyramidal cells with better arrangement and cell structure and decreased number of necrotic cells were also observed in hippocampal regions of TBI model rats with Bre treatments.

  Conclusion  Bre may alleviate TBI symptoms by down-regulating TNF-α, IL-1β, IL-8, IL-6, and MDA and up-regulating SOD and the regulations may be related to ROS-NLRP3 signaling pathway.