The neuroprotective effects of esculetin on the neurological scores, BBB permeability and brainwater content after severe traumatic braininjury in male rat: A behavioral study and biochemistry

Background and Aim : TBI pathogenesis is a complex process that results from primary and secondary injuries that lead to temporary or permanent neurological deficits. The secondary injury can happen from minutes to days from the primary impact and consists of a molecular, chemical, and inflammatory cascade responsible for further cerebral damage. Esculetin (6, 7-dihydroxycoumarin) is a natural coumarin compound isolated from various plant species, such as Cichorium intybus .Esculetin possesses multifarious pharmacological activities, including anti-oxidant, anti-inflammatory and hepatoprotective effects. Therefore, in this study, we investigated the effects of neuroprotective esculetin after severe traumatic brain injury in male rats.Methods : The male Albino wistar rats received different doses of esculetin (1, 2, 4 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 using a weight 450 gr by Marmarou method. The neurologic scores (VCS) and brain water content, the beam-walk –balance task (WB) and BBB integrity (Evans blue) were recorded for three days. At the end of the third day from deep anaesthetized animals CSF was collected from cisterna magna and then analysis MMP-9 with Elisa assay.Results : Our results showed that following TBI, cerebral edema, cerebrospinal fluid, neurological scores and Vestibulomotor function become defective and MMP-9 increases in compare with intact-sham control groups (P<0.001) but IP injection esculetin in dose -response manner improved above neurology dysfunctions and decreases MMP-9 but in 4 mg/kg dose results were better in compare with TBI-saline control groups (P<0.001).Conclusion : These findings showed that esculetin has beneficial neuroprotective effects on the neurological scores, , neural repair and brain edema also it can decrease MMP-9 and BBB permeability after traumatic brain injury.

Keywords:

esculetin , TBI , neuroprotection , blood brain-barrier , rat