2-(2-Benzofuranyl)-2-Imidazoline Mediates Neuroprotection by Regulating the Neurovascular Unit Integrity in a Rat Model of Focal Cerebral Ischemia

Abstract

We showed previously that 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a ligand to type 2 imidazoline receptor (I2R) exerts neuroprotective effects in ischemia stroke via an unknown mechanism. The present study was to investigate whether 2-BFI can protect the neurovascular unit (NVU) using a rat model of 90 min focal cerebral ischemia. Rats were randomly divided into three groups: thesham-operated group; the vehicle control group and the 2-BFI group which received 2-BFI (3 mg/kg) immediately after the start of middle cerebralartery occlusion (MCAO). Neurological deficit score, infarct size, apoptosis level, brain water content and Evans Blue extravasation were assessed at 24 h after stroke. Expressions of occludin and zonula occludens 1 (ZO-1), collagen IV, aquaporin-4 (AQP-4), matrix metalloproteinase-9 (MMP-9) and MMP-2 were assessed by Western blotting. 2-BFI treatment was associated with significant improvement of neurological performance and decreased infarct volume at 24 h after stroke. Apoptosis level reduced significantly by 2-BFI compared to the vehicle group (34.3 ± 5.4% vs 56.1 ± 7.9%, p < 0.05). Significant decreased of brain water content (79.5 ± 2.6% vs 84.62 ± 2%, p < 0.05) and Evans Blue extravasation (1.2 ± 0.5 vs 2.5 ± 0.41 µg/g, p < 0.05) of ipsilateral hemisphere was observed in 2-BFI group compared to vehicle group. Expressions of occludin, ZO-1 and collagen IV were significantly higher while MMP-9 level significantly lower in 2-BFI group. AQP-4 and MMP-2 showed no difference between 2-BFI and the vehicle groups. These results suggest that the neuroprotective effects of 2-BFI in acute ischemic brain damage are at least partly due to the drug's ability to improve the functions of NVU.