Abstract 194: BDNF Knockdown Abrogates AT1 Blockade -Induced Improvement in Stroke Outcome
Background: Brain derived neurotrophic factor has been shown to play an important role in long term functional recovery after stroke. Unfortunately, the clinical exploitation of this protein is limited due to the lack of pharmacological interventions that regulate its expression. Angiotensin II receptor blockers (ARBs) increase BDNF expression in both normotensive and hypertensive animals. We investigated the possible interaction between acute ARB treatment and BDNF in terms of long term functional recovery after stroke.
Methods: Male normotensive wistar rats received bilateral ICV injections with lentiviruses expressing either BDNF shRNA or vector. 14 days after injection, animals were subjected to 90 minutes MCAO and randomized to either candesartan 1mg/kg or saline at the time of reperfusion. Functional recovery was assessed 24 hours after stroke and every 72 hours for 14 days using a blinded battery of validated behavioral tests. Animals were then sacrificed and their brains processed for immunohistochemistry.
Results: Bilateral injection with shRNA reduced the expression of BDNF by more than 70% (p=0.0045). Acute ARB administration ameliorated stroke induced functional deficits throughout the follow-up period after stroke in all used tests and Day 14 data is shown on the Table. This pro-recovery effect was totally ablated in BDNF knocked down animals. Acute ARB therapy also increased the number of new brain blood vessels (CD31/Ki67 positive cells) which was also BDNF dependent.
Acute ARB- induced functional recovery after stroke is BDNF dependent.
This pro-recovery effect is associated with a BDNF dependent proangiogenic state.
Table 1: Experimental data summary. SD are shown in parenthesis. a,b,c. Pairs of means with different letters are significantly different from each other
Author Disclosures: A. Alhusban: None. A. Fouda: None. B. Pillai: None. A. Ergul: Research Grant; Significant; American Heart Association Established Investigator 0740002N, NS054688. S.C. Fagan: Research Grant; Significant; RO1-NS063965, VA Merit Review (BX000891). Consultant/Advisory Board; Significant; Consultant for Pfizer, Inc., Consultant for Genetech, Inc..
- © 2014 by American Heart Association, Inc.