The Nobiletin neuroprotective effects on the neurological scores, blood brain barrier permeability and brain edema after severe traumatic brain injury in male rat: A behavioral, Biochemical study

Background and Aim : Traumatic brain injury (TBI) is one of the major causes of mortality and neurological disability. TBI has been classified into primary injury and secondary injury, and the latter plays a crucial role in the clinical outcome of patients with TBI. Nobiletin is a flavonoid that present in the peels of citrus fruits. Nobiletin possesses several bioactive properties activities as antioxidant, anti-inflammatory, neuroprotective, and anti-proliferative properties. Therefore, in this study, we investigated the effects of neuroprotective Nobiletin after severe traumatic brain injury in male ratsMethods : The male Albino wistar rats received different doses of nobiletin (25, 50, 100 mg/kg, i.p.). All animals were intubated before surgery. In the TBI groups except sham and intact control groups, diffuse TBI was induced by Marmarou method using a TBI induction device. The severe TBI was induced using a weight 450 gr. The neurologic scores (VCS) and brain water content, the beam-walk –balance task (WB) and BBB integrity (Evans blue) were recorded for D1, D2 and D3 after TBI day. At the end of the third day, from cisterna magna deep anaesthetized animals CSF was collected fixed in Liquid nitrogen for analysis IL-1β and IL-10 with Elisa assay.Results : Our results showed a significant reduction in brain water content , blood brain barrier permeability and beam balance, and a significant increase in VCS and beam walk of treatment groups as dose response manner in compared to vehicle and TBI control groups (P<0.001). Nobiletin in two dose (25 and 50 mg/kg) improved neurology, biochemical disorder but in 100 mg/kg dose results did not significant in compare with TBI-saline control groups (P> 0.05).Conclusion : These findings showed that nobiletin may implicate a critical role in promoting inflammation and aggravating damage after TBI. Post TBI administration nobiletin revealed significant improvement in biochemical and neurological outcomes in experimental TBI. The underlying mechanism(s) was not determined and needs further investigation.

Keywords:

Nobiletin , TBI , neuroprotection , anti-inflammation , rat