Silencing VEGF-B Diminishes the Neuroprotective Effect of Candesartan Treatment After Experimental Focal Cerebral Ischemia
The pro-survival effect of VEGF-B has been documented in different in vivo and in vitro models. We have previously shown an enhanced VEGF-B expression in response to candesartan treatment after focal cerebral ischemia. In this study, we aimed to silence VEGF-B expression to assess its contribution to candesartan's benefit on stroke outcome. Silencing VEGF-B expression was achieved by bilateral intracerebroventricular injections of lentiviral particles containing short hairpin RNA (shRNA) against VEGF-B. Two weeks after lentiviral injections, rats were subjected to either 90 min or 3 h of middle cerebral artery occlusion (MCAO) and randomized to intravenous candesartan (1 mg/kg) or saline at reperfusion. Animals were sacrificed at 24 or 72 h and brains were collected and analyzed for hemoglobin (Hb) excess and infarct size, respectively. Functional outcome at 24, 48 and 72 h was assessed blindly. Candesartan treatment improved neurobehavioral and motor function, and decreased infarct size and Hb. While silencing VEGF-B expression diminished candesartan's neuroprotective effect, candesartan-mediated vascular protection was maintained even in the absence of VEGF-B suggesting that this growth factor is not the mediator of candesartan's vascular protective effects. However, VEGF-B is a mediator of neuroprotection achieved by candesartan and represents a potential drug target to improve stroke outcome. Further studies are needed to elucidate the underlying molecular mechanisms of VEGF-B in neuroprotection and recovery after ischemic stroke.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
|---|---|
| Enthalten in: |
Neurochemical research - 43(2018), 10 vom: 08. Okt., Seite 1869-1878 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ishrat, Tauheed [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 14.01.2019 Date Revised 06.09.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s11064-018-2604-x |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM287274691 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM287274691 | ||
| 003 | DE-627 | ||
| 005 | 20231225053640.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s11064-018-2604-x |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0957.xml |
| 035 | |a (DE-627)NLM287274691 | ||
| 035 | |a (NLM)30088238 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ishrat, Tauheed |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Silencing VEGF-B Diminishes the Neuroprotective Effect of Candesartan Treatment After Experimental Focal Cerebral Ischemia |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.01.2019 | ||
| 500 | |a Date Revised 06.09.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The pro-survival effect of VEGF-B has been documented in different in vivo and in vitro models. We have previously shown an enhanced VEGF-B expression in response to candesartan treatment after focal cerebral ischemia. In this study, we aimed to silence VEGF-B expression to assess its contribution to candesartan's benefit on stroke outcome. Silencing VEGF-B expression was achieved by bilateral intracerebroventricular injections of lentiviral particles containing short hairpin RNA (shRNA) against VEGF-B. Two weeks after lentiviral injections, rats were subjected to either 90 min or 3 h of middle cerebral artery occlusion (MCAO) and randomized to intravenous candesartan (1 mg/kg) or saline at reperfusion. Animals were sacrificed at 24 or 72 h and brains were collected and analyzed for hemoglobin (Hb) excess and infarct size, respectively. Functional outcome at 24, 48 and 72 h was assessed blindly. Candesartan treatment improved neurobehavioral and motor function, and decreased infarct size and Hb. While silencing VEGF-B expression diminished candesartan's neuroprotective effect, candesartan-mediated vascular protection was maintained even in the absence of VEGF-B suggesting that this growth factor is not the mediator of candesartan's vascular protective effects. However, VEGF-B is a mediator of neuroprotection achieved by candesartan and represents a potential drug target to improve stroke outcome. Further studies are needed to elucidate the underlying molecular mechanisms of VEGF-B in neuroprotection and recovery after ischemic stroke | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Angiotensin II type-1 receptor blocker (ARB) | |
| 650 | 4 | |a Candesartan | |
| 650 | 4 | |a Neuroprotection | |
| 650 | 4 | |a Stroke | |
| 650 | 4 | |a Vascular endothelial growth factor-B (VEGF-B) | |
| 650 | 7 | |a Benzimidazoles |2 NLM | |
| 650 | 7 | |a Biphenyl Compounds |2 NLM | |
| 650 | 7 | |a Neuroprotective Agents |2 NLM | |
| 650 | 7 | |a Tetrazoles |2 NLM | |
| 650 | 7 | |a Vascular Endothelial Growth Factor B |2 NLM | |
| 650 | 7 | |a candesartan |2 NLM | |
| 650 | 7 | |a S8Q36MD2XX |2 NLM | |
| 700 | 1 | |a Soliman, Sahar |e verfasserin |4 aut | |
| 700 | 1 | |a Eldahshan, Wael |e verfasserin |4 aut | |
| 700 | 1 | |a Pillai, Bindu |e verfasserin |4 aut | |
| 700 | 1 | |a Ergul, Adviye |e verfasserin |4 aut | |
| 700 | 1 | |a Fagan, Susan C |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Neurochemical research |d 1976 |g 43(2018), 10 vom: 08. Okt., Seite 1869-1878 |w (DE-627)NLM000294934 |x 1573-6903 |7 nnns |
| 773 | 1 | 8 | |g volume:43 |g year:2018 |g number:10 |g day:08 |g month:10 |g pages:1869-1878 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s11064-018-2604-x |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 43 |j 2018 |e 10 |b 08 |c 10 |h 1869-1878 | ||