Efficacy and Safety of Early Anti-inflammatory Drug Therapy for Secondary Injury in Traumatic Brain Injury

BACKGROUND: Brain injury following head trauma oc-curs in 2 stages, namely an early stage attributable to mechanical damage and a delayed stage resulting pri-marily from neuroinflammation. In this study, we examined early proinflammatory cytokine upregulation in an animal model of traumatic brain injury (TBI) and examined the effects of early anti-inflammatory therapy on neuro-inflammation, neuropathology, and systemic inflammatory activity. -METHODS: Seven-week-old C57BL/6 mice (20 g-25 g) were subjected to sham treatment or closed skull impact from a 30-g round weight dropped 15 cm onto the cortical midpoint. Model mice were then randomly assigned to receive intraperitoneal phosphate-buffered saline (control), 20 mg/kg cyclosporine A, 2 mg/kg dexamethasone, or 5 mg/ kg cholecalciferol 1 hour post-TBI. Body weight, brain weight, cytokine expression in the brain and draining lymph nodes (DLNs), and histopathological changes were measured at multiple times post-TBI. -RESULTS: Body weight did not significantly differ among the groups, whereas the brain-to-body weight ratio was significantly lower in the control group 7 days post-TBI. The peak expression of tumor necrosis factor -a, inter-leukin (IL)-1b, and IL-6 in the brain and DLNs 6 hours post-TBI was significantly lower in the dexamethasone and cyclosporine A groups. Conversely, peak IL-10 expression in the brain and DLNs was elevated in the cholecalciferol group. Control mice exhibited earlier and more severe neuroinflammatory damage than those in the experimental groups. -CONCLUSIONS: The administration of anti-inflammatory drugs or vitamin D analogs in the early period following TBI might help to reduce secondary injury from neuroinflammation.

Automated summary

This study examined the upregulation of proinflammatory cytokines in an animal model of traumatic brain injury (TBI) and the effects of early anti-inflammatory therapy. The results suggest that administering anti-inflammatory drugs or vitamin D analogs in the early stage following TBI can help reduce secondary injury from neuroinflammation.