Therapeutic Treatment with Pycnogenol? Attenuates Ischemic Brain Injury in Gerbils Focusing on Cognitive Impairment, Neuronal Death, BBB Leakage and Neuroinflammation in the Hippocampus

초록

Background: A gerbil model of ischemia and reperfusion (IR) injury in the forebrain has been developed for studies on mechanisms, prevention and therapeutic strategies of IR injury in the forebrain. Pycnogenol (R) (PYC), a standardized extract of French maritime pine tree (Pinus pinaster Aiton) has been exploited as an additive for dietary supplement. In the present study, we investigated the neuroprotective effects of post-treatment with PYC and its therapeutic mechanisms in gerbils. Methods: The gerbils were given sham and IR operation and intraperitoneally injected with vehicle and Pycnogenol (R) (25, 50 and 100 mg/kg, respectively) immediately, at 24 hours and 48 hours after sham and IR operation. Through 8-arm radial maze test and passive avoidance test, each spatial memory and short-term memory function was assessed. To examine the neuroprotection of Pycnogenol (R), we conducted cresyl violet staining, immunohistochemistry for neuronal nuclei, and Fluoro-Jade B histofluorescence. Moreover, we carried out immunohistochemistry for immunoglobulin G (IgG) to investigate blood-brain barrier (BBB) leakage and interleukin-1 beta (IL-1 beta) to examine change in pro-inflammatory cytokine. Results: We found that IR-induced memory deficits were significantly ameliorated when 100 mg/kg Pycnogenol (R) was treated. In addition, treatment with 100 mg/kg Pycnogenol (R), not 25 mg/kg nor 50 mg/kg, conferred neuroprotective effect against IR injury. For its mechanisms, we found that 100 mg/kg Pycnogenol (R) significantly reduced BBB leakage and inhibited the expression of IL-1 beta. Conclusions: Therapeutic treatment (post-treatment) with Pycnogenol (R) after IR effectively attenuated ischemic brain injury in gerbils. Based on these results, we suggest that PYC can be employed as an important material for ischemic drugs.

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