Abstract TP329: Continuous Intracerebroventicular Injection of Brain-derived Neurotrophic Factor Increases Stroke Onset via Elevation of Blood Pressure in Hypertensive Rats

Abstract

Introduction: Increasing evidences describe that Brain-derived neurotrophic factor (BDNF) is neuroprotective against cerebrovascular injuries and we previously revealed BDNF preservation on cerebral vessels was associated with inhibition of stroke onset in hypertensive rats. As BDNF was reported to increase blood pressure (BP) in hypertension, however, the upregulation might show conflicting results regarding stroke onset. In this study, we pursued the role of BDNF on stroke onset induced by high-salt diet (HSD) in hypertensive rats. Methods: In experiment 1, spontaneously hypertensive stroke-prone rats (SHRSP) were fed an 8% (n=22) or 0.3% (n=8) sodium diet from 11 weeks of age through 28 days. In experiment 2, SHRSP were treated with continuous intracerebroventricular injection of 2.1μg/day BDNF (n=10) or the vehicle (PBS; n=10) and fed an 8% sodium diet from 11 weeks of age through 24 days. Results and Conclusions: In experiment 1, stroke onset (95%) and mortality (55%) were frequently seen in the rats with HSD, whereas the rats with normal-salt diet were healthy. The expression level of BNDF was upregulated in the cerebral hemisphere and the increase were seen in reactive astrocytes at somatosensory cortex, whereas it was downregulated in endothelial cells. In experiment 2, in comparison with vehicle group, SHRSP with BDNF showed significant increase of incidence of stroke signs (60% vs. 89%), mortality (20% vs. 67%), BP at 2 weeks (214±6 vs. 244±12 mmHg), heart rate (366±20 vs. 457±17 beat/min) and decrease of body weight at 2 week (253±6 vs. 212±11 g), symptom score (5.6±0.3 vs. 2.8±0.8), and gastrocnemius muscle/BW (57±1 vs. 53±1 mg/g). Conclusion Despite the consistent observations of protective roles of BDNF in endothelial cells against the stroke, the present study demonstrated that endogenous BDNF was produced in reactive astrocytes in relation to stroke onset and additive application of exogenous BDNF by continuous intracerebroventricular injection enhanced the onset via elevation of BP in hypertensive rats. As BDNF is a potential candidate treatment not only for post-stroke but also stroke inhibition, we suggest that hypertensive patients need care for the elevation of BP in the clinical trials with BDNF.