PMID- 25084762
OWN - NLM
STAT- MEDLINE
DCOM- 20160308
LR  - 20220318
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 51
IP  - 3
DP  - 2015
TI  - Low-dose candesartan enhances molecular mediators of neuroplasticity and 
      subsequent functional recovery after ischemic stroke in rats.
PG  - 1542-53
LID - 10.1007/s12035-014-8830-6 [doi]
AB  - We have previously reported that angiotensin type 1 receptor (AT1R) blockade with 
      candesartan exerts neurovascular protection after experimental cerebral ischemia. 
      Here, we tested the hypothesis that a low, subhypotensive dose of candesartan 
      enhances neuroplasticity and subsequent functional recovery through enhanced 
      neurotrophic factor expression in rats subjected to ischemia reperfusion injury. 
      Male Wistar rats (290-300 g) underwent 90 min of middle cerebral artery occlusion 
      (MCAO) and received candesartan (0.3 mg/kg) or saline at reperfusion and then 
      once every 24 h for 7 days. Functional deficits were assessed in a blinded manner 
      at 1, 3, 7, and 14 days after MCAO. Animals were sacrificed 14-day post-stroke 
      and the brains perfused for infarct size by cresyl violet. Western blot and 
      immunohistochemistry were used to assess the expression of growth factors and 
      synaptic proteins. Candesartan-treated animals showed a significant reduction in 
      the infarct size [t (13) = -5.5, P = 0.0001] accompanied by functional recovery 
      in Bederson [F (1, 13) = 7.9, P = 0.015], beam walk [F (1, 13) = 6.7, P = 0.023], 
      grip strength [F (1, 13) = 15.2, P = 0.0031], and rotarod performance [F (1, 
      14) = 29.8, P < 0.0001]. In addition, candesartan-treated animals showed 
      significantly higher expression of active metalloproteinase-3 (MMP-3), laminin, 
      and angiopoietin-1 (Ang-1). The expression of vascular endothelial growth factor 
      (VEGF) and brain-derived neurotrophic factor (BDNF) and its receptor was 
      significantly increased in the animals treated with candesartan. Also, we 
      observed significant increases in neuroplasticity markers, synaptophysin, and 
      PSD-95. These results indicate that low-dose candesartan had a large and enduring 
      effect on measures of plasticity, and this accompanied the functional recovery 
      after ischemic stroke.
FAU - Ishrat, Tauheed
AU  - Ishrat T
AD  - Charlie Norwood VA Medical Center, Augusta, GA, USA, tauheedarshi@gmail.com.
FAU - Pillai, Bindu
AU  - Pillai B
FAU - Soliman, Sahar
AU  - Soliman S
FAU - Fouda, Abdelrahman Y
AU  - Fouda AY
FAU - Kozak, Anna
AU  - Kozak A
FAU - Johnson, Maribeth H
AU  - Johnson MH
FAU - Ergul, Adviye
AU  - Ergul A
FAU - Fagan, Susan C
AU  - Fagan SC
LA  - eng
GR  - NS054688/NS/NINDS NIH HHS/United States
GR  - R01 NS063965/NS/NINDS NIH HHS/United States
GR  - NS063965/NS/NINDS NIH HHS/United States
GR  - R01 NS083559/NS/NINDS NIH HHS/United States
GR  - I01 BX000347/BX/BLRD VA/United States
GR  - R03 NS054688/NS/NINDS NIH HHS/United States
GR  - I01 BX000891/BX/BLRD VA/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140802
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Benzimidazoles)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Tetrazoles)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - S8Q36MD2XX (candesartan)
SB  - IM
MH  - Animals
MH  - Benzimidazoles/administration & dosage/*pharmacology
MH  - Biphenyl Compounds
MH  - Brain Ischemia/*drug therapy
MH  - Disease Models, Animal
MH  - Male
MH  - Neuronal Plasticity/*drug effects
MH  - Rats, Wistar
MH  - Recovery of Function/*drug effects
MH  - Stroke/*drug therapy
MH  - Tetrazoles/administration & dosage/*pharmacology
MH  - Vascular Endothelial Growth Factor A/metabolism
PMC - PMC4677667
MID - NIHMS736110
COIS- Conflict of Interest SCF is a consultant for and has received funding from 
      Pfizer. The contents do not represent the views of the Department of Veterans 
      Affairs or the United States Government.
EDAT- 2014/08/03 06:00
MHDA- 2016/03/10 06:00
PMCR- 2016/06/01
CRDT- 2014/08/03 06:00
PHST- 2014/06/17 00:00 [received]
PHST- 2014/07/22 00:00 [accepted]
PHST- 2014/08/03 06:00 [entrez]
PHST- 2014/08/03 06:00 [pubmed]
PHST- 2016/03/10 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - 10.1007/s12035-014-8830-6 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2015;51(3):1542-53. doi: 10.1007/s12035-014-8830-6. Epub 2014 Aug 
      2.