Abstract W MP89: Silencing VEGF-B Diminishes the Neuroprotective Effect of Candesartan Treatment after Experimental Focal Cerebral Ischemia

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Sahar Soliman ◽  
Tauheed Ishrat ◽  
Bindu Pillai ◽  
Adviye Ergul ◽  
Susan C Fagan
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Critical Role ◽  
Hemoglobin Content

Background & Objective: 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 tested the hypothesis that VEGF-B expression contributes to candesartan-mediated recovery. Methods: Silencing VEGF-B expression was achieved by bilateral intracerebroventricular injection of lentiviral particles containing short hairpin RNA against VEGF-B (KD) or vehicle (NTC). Middle cerebral artery (MCA) was occluded for 90 minutes. At reperfusion, animals received either intravenous saline or candesartan. Neurobehavioral outcome was assessed 24, 48 and 72 hours after the insult and infarct size was measured at 72 hours. In an additional set of experiment, middle cerebral artery was occluded for 3h followed by 21h reperfusion. Rats were sacrificed at 24h post-MCAO and brains perfused for evaluation of vascular markers (edema and hemoglobin content). Results (Table): Candesartan-treated animals showed a significant reduction in the infarct size and edema accompanied by functional recovery in Bederson, beam walk, paw grasp and grip strength performance only in the presence of VEGF-B. In addition, candesartan-treated animals showed significantly reduction of hemoglobin content, a marker for hemorrhage and edema at 24 h after MCAO. Conclusion: Our results suggest VEGF-B plays a critical role in mediating candesartan’s neuronal and vascular protective effect after stroke. Identifying growth factors that mediate recovery after ischemic stroke presents possible targets for stroke therapeutics.

The Neuroprotective Effect of Xenon Administration during Transient Middle Cerebral Artery Occlusion in Mice

2003 ◽  
Vol 99 (4) ◽  
pp. 876-881 ◽  
Author(s):  
H. Mayumi Homi ◽  
Noriko Yokoo ◽  
Daqing Ma ◽  
David S. Warner ◽  
Nicholas P. Franks ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Artery Occlusion ◽  
Cerebral Infarct ◽  
Cerebral Artery Occlusion

Background Xenon has been shown to be neuroprotective in several models of in vitro and in vivo neuronal injury. However, its putative neuroprotective properties have not been evaluated in focal cerebral ischemia. The purpose of this study was to determine if xenon offers neuroprotection in a mouse model of middle cerebral artery occlusion. Methods C57BL/6 mice underwent 60 min of middle cerebral artery occlusion. The animals (n = 21 per group) were randomized to receive either 70% xenon + 30% O2, 70% N2O + 30% O2, or 35% xenon + 35% N2O + 30% O2. After 24 h, functional neurologic outcome (on three independent scales: four-point, general, and focal deficit scales) and cerebral infarct size were evaluated. Results The 70% xenon + 30% O2 group showed improved functional outcome (median [interquartile range], four-point scale: 2 [2], 70% xenon + 30% O2 versus 3 [2], 70% N2O + 30% O2, P = 0.0061; general deficit scale: 9 [6], 70% xenon + 30% O2 versus 10 [4], 70% N2O + 30% O2, P = 0.0346). Total cerebral infarct volumes were reduced in the 70% xenon + 30% O2 group compared with the 70% N2O + 30% O2 group (45 +/- 17 mm3 versus 59 +/- 11 mm3, respectively; P = 0.0009). Conclusions In this model of transient focal cerebral ischemia, xenon administration improved both functional and histologic outcome.

scholarly journals Neuroprotective Effect of the AMPA Receptor Antagonist LY-293558 in Focal Cerebral Ischemia in the Cat

1994 ◽  
Vol 14 (3) ◽  
pp. 466-471 ◽  
Author(s):  
R. Bullock ◽  
D. I. Graham ◽  
S. Swanson ◽  
J. McCulloch
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Receptor Antagonist ◽  
Ampa Receptor ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Ischemic Damage ◽  
Physiological Variables ◽  
Ampa Receptor Antagonist

The effects of the glutamate α-amino-3-hydroxy 5-methyl-4-isoxazole propionate (AMPA) receptor antagonist LY-293558 in reducing ischemic brain damage have been assessed in halothane-anesthetized cats. Focal cerebral ischemia was produced by permanent occlusion of one middle cerebral artery, and the animals were killed 6 h later. The amount of early irreversible ischemic damage was assessed at 16 predetermined stereotactic planes by an observer blinded to treatment paradigm employed. Treatment with LY-293558 (15 mg/kg i.v., plus infusion of 7 mg/kg/h) initiated 30 min prior to middle cerebral artery occlusion reduced significantly (p < 0.02) the volume of ischemic damage (from 3,423 ± 212 mm3 of the cerebral hemisphere in vehicle-treated cats to 2,822 ± 569 mm3 in LY-293558-treated cats). The present data demonstrate that an AMPA receptor antagonist can reduce focal ischemic damage in a gyrencephalic species in which key physiological variables have been controlled and monitored throughout the postischemic period. These data provide additional support for the clinical evaluation of AMPA receptor antagonists in focal cerebral ischemia in humans.

scholarly journals Neuroprotective Effect of Smilacis chinae Rhizome on NMDA-Induced Neurotoxicity In Vitro and Focal Cerebral Ischemia In Vivo

2008 ◽  
Vol 106 (1) ◽  
pp. 68-77 ◽  
Author(s):  
Ju Yeon Ban ◽  
Soon Ock Cho ◽  
Sun-Ha Choi ◽  
Hyun Soo Ju ◽  
Ju Yeon Kim ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect

scholarly journals Effects of Cerebral Ischemia on Neuronal Hemoglobin

2008 ◽  
Vol 29 (3) ◽  
pp. 596-605 ◽  
Author(s):  
Yangdong He ◽  
Ya Hua ◽  
Wenquan Liu ◽  
Haitao Hu ◽  
Richard F Keep ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Ischemic Preconditioning ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Sprague Dawley ◽  
Cerebral Neurons

This study examined whether neuronal hemoglobin (Hb) is present in rats. It then examined whether cerebral ischemia or ischemic preconditioning (IPC) affects neuronal Hb levels in vivo and in vitro. In vivo, male Sprague-Dawley rats were subjected to either 15 mins of transient middle cerebral artery occlusion (MCAO) with 24 h of reperfusion, an IPC stimulus, or 24 h of permanent MCAO (pMCAO), or IPC followed 3 days later by 24 h of pMCAO. In vitro, primary cultured neurons were exposed to 2 h of oxygen—glucose deprivation (OGD) with 22 h of reoxygenation. Results showed that Hb is widely expressed in rat cerebral neurons but not astrocytes. Hemoglobin expression was significantly upregulated in the ipsilateral caudate and the cortical core of the middle cerebral artery territory after IPC. Hemoglobin levels also increased more in the penumbral cortex and the contralateral hemisphere 24 h after pMCAO, but expressions in the ipsilateral caudate and the cortical core area were decreased. Ischemic preconditioning modified pMCAO-induced brain Hb changes. Neuronal Hb levels in vitro were increased by 2 h of OGD and 22 h of reoxygenation. These results indicate that Hb is synthesized in neurons and can be upregulated by ischemia.

High-soy diet decreases infarct size after permanent middle cerebral artery occlusion in female rats

2005 ◽  
Vol 289 (1) ◽  
pp. R103-R108 ◽  
Author(s):  
Derek A. Schreihofer ◽  
Khoi D. Do ◽  
Ann M. Schreihofer
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Neurological Deficit ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Estrogen Treatment ◽  
Cerebral Artery Occlusion

Estrogen is a powerful neuroprotective agent in rodent models of ischemic stroke. However, in humans, estrogen treatment can increase risk of stroke. Health risks associated with hormone replacement have led many women to consider alternative therapies including high-soy diets or supplements containing soy isoflavones, which act as estrogen receptor ligands to selectively mimic some of estrogen's actions. We hypothesized that a high-soy diet would share the neuroprotective actions of estrogen in focal cerebral ischemia. Female Sprague-Dawley rats were ovariectomized and divided into three groups: isoflavone-free diet + placebo (IF-P), isoflavone-free diet + estradiol (IF-E), or high-soy diet + placebo (S-P). Two weeks after being placed on diets, rats underwent left permanent middle cerebral artery occlusion (MCAO). Reductions in ipsilateral cerebral blood flow were equivalent across groups (∼50%). Twenty-four hours later neurological deficit was determined, and brains were collected for assay of cerebral infarct by TTC staining. In the IF-P rats MCAO produced a 50 ± 4% cerebral infarct. Estrogen and high-soy diet both significantly reduced the size of the infarcts to 26 ± 5% in IF-E rats and to 37 ± 5% in S-P rats. Analysis at five rostro-caudal levels revealed that estrogen treatment was slightly more effective at reducing infarct size than high soy diet. Overall neurological deficit scores at 24 h correlated with infarct size; however, there were no statistically significant differences among the treatment groups. These data show that 2 wk of a high-soy diet is an effective prophylactic strategy for reducing stroke size in a rat model of focal cerebral ischemia.

Sign in / Sign up

Export Citation Format

Share Document