Neuroprotective effect of dauricine in cortical neuron culture exposed to hypoxia and hypoglycemia: involvement of correcting perturbed calcium homeostasis

2007 ◽  
Vol 85 (6) ◽  
pp. 621-627 ◽  
Author(s):  
Yan-Hong Li ◽  
Pei-Li Gong
Keyword(s):  
Cerebral Ischemia ◽  
Cortical Neurons ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Primary Cultures ◽  
Trypan Blue Exclusion ◽  
Trypan Blue Exclusion Method ◽  
Fluorescence Measurements

We have previously reported that dauricine protects brain tissues from focal cerebral ischemia. To corroborate this effect, neurotoxicity due to hypoxia and hypoglycemia was assessed in primary cultures of rat cortical neurons by using a trypan blue exclusion method. To further clarify the mechanism, the intracellular Ca2+ concentration ([Ca2+]i) and mitochondrial membrane potential (ΔΨm) of dissociated rat cortical cells were monitored by fura-2 fluorescence measurements and flow cytometry, respectively. The results showed that 1 and 10 μmol/L dauricine significantly enhanced neuronal survival during 4 h of hypoxia and hypoglycemia. Dauricine inhibited the increase in [Ca2+]i and decrease in ΔΨm induced by 30 min of hypoxia and hypoglycemia. When exploring the pathway, we found that 1 μmol/L dauricine inhibited the [Ca2+]i increase induced by 7.5 nmol/L thapsigargin in either the presence or absence of extracellular Ca2+ and by 1 mmol/L l-glutamate in the presence of extracellular Ca2+. These results suggest that dauricine prevents neuronal loss from ischemia in vitro, which is in accordance with our previous research in vivo. In addition, by inhibiting Ca2+ release from the endoplasmic reticulum and Ca2+ influx from the extracellular space, dauricine suppressed the increase in [Ca2+]i and, subsequently, the decrease in ΔΨm induced by hypoxia and hypoglycemia. This effect may underlie the mechanism of action of dauricine on cerebral ischemia.

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 Altered Biosynthesis of Neuropeptide Processing Enzyme Carboxypeptidase E after Brain Ischemia: Molecular Mechanism and Implication

2004 ◽  
Vol 24 (6) ◽  
pp. 612-622 ◽  
Author(s):  
An Zhou ◽  
Manabu Minami ◽  
Xiaoman Zhu ◽  
Sylvia Bae ◽  
John Minthorne ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Ischemia ◽  
Cortical Neurons ◽  
Focal Cerebral Ischemia ◽  
Proteolytic Processing ◽  
Carboxypeptidase E ◽  
Processing Enzyme ◽  
The Impact

In this study, using both in vivo and in vitro ischemia models, the authors investigated the impact of brain ischemia on the biosynthesis of a key neuropeptide-processing enzyme, carboxypeptidase E (CPE). The response to brain ischemia of animals that lacked an active CPE was also examined. Combined in situ hybridization and immunocytochemical analyses for CPE showed reciprocal changes of CPE mRNA and protein, respectively, in the same cortical cells in rat brains after focal cerebral ischemia. Western blot analysis revealed an accumulation of the precursor protein of CPE in the ischemic cortex in vivo and in ischemic cortical neurons in vitro. Detailed metabolic labeling experiments on ischemic cortical neurons showed that ischemic stress caused a blockade in the proteolytic processing of CPE. When mice lacking an active CPE protease were subjected to a sublethal episode of focal cerebral ischemia, abundant TUNEL-positive cells were seen in the ischemic cortex whereas only a few were seen in the cortex of wild-type animals. These findings suggest that ischemia has an adverse impact on the neuropeptide-processing system in the brain and that the lack of an active neuropeptide-processing enzyme exacerbates ischemic brain injury.

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.

scholarly journals Desferrioxamine Induces Delayed Tolerance against Cerebral Ischemia in Vivo and in Vitro

2002 ◽  
Vol 22 (5) ◽  
pp. 520-525 ◽  
Author(s):  
Konstantin Prass ◽  
Karsten Ruscher ◽  
Maria Karsch ◽  
Nikolay Isaev ◽  
Dirk Megow ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Cortical Neurons ◽  
Focal Cerebral Ischemia ◽  
Tolerance Induction ◽  
Transcriptional Response ◽  
Glucose Deprivation ◽  
Rats And Mice ◽  
Transcription Factor 1

The widely prescribed drug desferrioxamine is a known activator of the hypoxia-inducible transcription factor 1 (HIF-1) and the subsequent transcription of erythropoietin. In the brain, HIF-1 is a master switch of the transcriptional response to hypoxia, whereas erythropoietin is a potent neuroprotectant. The authors show that desferrioxamine dose-dependently and time-dependently induces tolerance against focal cerebral ischemia in rats and mice, and against oxygen–glucose deprivation in purified cortical neurons. Desferrioxamine induced HIF-1 DNA binding and transcription of erythropoietin in vivo, the temporal kinetics of which were congruent with tolerance induction. Desferrioxamine is a promising drug for the induction of tolerance in humans when ischemia can be anticipated.

Reduction in programmed cell death and improvement in functional outcome of transient focal cerebral ischemia after administration of granulocyte-macrophage colony-stimulating factor in rats

2009 ◽  
Vol 111 (1) ◽  
pp. 155-163 ◽  
Author(s):  
TaeHo Kong ◽  
Jung-Kyoung Choi ◽  
Hyeonseon Park ◽  
Byung Hyune Choi ◽  
Brian Jeffrey Snyder ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Locomotor Behavior ◽  
Gm Csf ◽  
Culture Model ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony

Object Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hematopoietic growth factor that both enhances the survival and drives the differentiation and proliferation of myeloid lineage cells. Recent studies have suggested that GM-CSF has a neuroprotective effect against CNS injury. In this paper, the authors investigated the neuroprotective effect of GM-CSF on neuron survival and locomotor behavior in a rat model of focal cerebral ischemic injury. Materials To understand its neuroprotective effect in vitro, GM-CSF was administered to a glutamate-induced excitotoxicity neuronal injury cell culture model that mimics the pathophysiology of focal hypoxic cerebral injury. In the animal study, the authors prepared a rat focal cerebral ischemia model by occluding the unilateral middle cerebral artery. They then examined the effects of GM-CSF administration on changes in infarct volume, apoptosis-related gene expression, and improvement in locomotor behavior. Results Treatment with GM-CSF significantly increased cell viability in a cell culture model of glutamate-induced neuronal injury. Furthermore, in vivo administration of GM-CSF at 60 μg/kg body weight daily for 5 consecutive days beginning immediately after injury decreased infarction volume, altered the expression of several apoptosis-related genes (Bcl-2, Bax, caspase 3, and p53), and improved locomotor behavior in the focal cerebral ischemia model. Conclusions The GM-CSF had neuroprotective effects in in vitro and in vivo experiments and resulted in decreased infarction volume and improved locomotor behavior. Although the specific mechanism involved in stroke recovery was not fully elucidated as it was not the primary focus of this study, administration of GM-CSF appeared to decrease the extent of neuronal apoptosis by modulating the expression of several apoptosis-related genes such as Bcl-2, Bax, caspase 3, and p53. Further investigations are necessary to better understand the role of GM-CSF on neural regeneration during the recovery phase of a stroke, as well as the intracellular signal transduction pathways that mediate neuroprotection.

Neuroprotective effect of astaxanthin on H2O2-induced neurotoxicity in vitro and on focal cerebral ischemia in vivo

2010 ◽  
Vol 1360 ◽  
pp. 40-48 ◽  
Author(s):  
Ya-Peng Lu ◽  
Si-Yuan Liu ◽  
Hua Sun ◽  
Xiao-Mei Wu ◽  
Jie-Jia Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect

scholarly journals Correlation of CGS 19755 Neuroprotection against in vitro Excitotoxicity and Focal Cerebral Ischemia

1995 ◽  
Vol 15 (5) ◽  
pp. 865-876 ◽  
Author(s):  
Miguel A. Pérez-Pinzón ◽  
Carolina M. Maier ◽  
Edward J. Yoon ◽  
Guo-Hua Sun ◽  
Rona G. Giffard ◽  
...  
Keyword(s):  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Primary Cultures ◽  
Arterial Occlusion ◽  
Neuroprotective Effects ◽  
Brain Levels ◽  
Cgs 19755

The in vivo neuroprotective effect and brain levels of cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755), a competitive N-methyl-D-aspartate (NMDA) antagonist, were compared with its in vitro neuroprotective effects. The dose-response for in vitro neuroprotection against both NMDA toxicity and combined oxygen-glucose deprivation (OGD) was determined in murine neocortical cultures. Primary cultures of neocortical cells from fetal mice were injured by exposure to 500 μM NMDA for 10 min or to OGD for 45 min. The effect of CGS 19755 in both injury paradigms was assessed morphologically and quantitated by determination of lactate dehydrogenase release. Near complete neuroprotection was found at high doses of CGS 19755. The ED50 for protection against NMDA toxicity was 25.4 μmM, and against OGD the ED50 was 15.2 μM. For the in vivo paradigm rabbits underwent 2 h of left internal carotid, anterior cerebral, and middle cerebral artery occlusion followed by 4 h reperfusion; ischemic injury was assessed by magnetic resonance imaging and histopathology. The rabbits were treated with 40 mg/kg i.v. CGS 19755 or saline 10 min after arterial occlusion. CSF and brain levels of CGS 19755 were 12 μM and 5 μM, respectively, at 1 h, 6 μM and 5 μM at 2 h, and 13 μM and 7 μM at 4 h. These levels were neuroprotective in this model, reducing cortical ischemic edema by 48% and ischemic neuronal damage by 76%. These results suggest that a single i.v. dose penetrates the blood-brain barrier, attaining sustained neuroprotective levels that are in the range for in vitro neuroprotection.

scholarly journals Neuroprotection by Brazilian Green Propolis againstIn vitroandIn vivoIschemic Neuronal Damage

2005 ◽  
Vol 2 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Masamitsu Shimazawa ◽  
Satomi Chikamatsu ◽  
Nobutaka Morimoto ◽  
Satoshi Mishima ◽  
Hiroichi Nagai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Brain Infarction ◽  
Folk Medicine ◽  
Neuroprotective Function ◽  
Brazilian Green Propolis

We examined whether Brazilian green propolis, a widely used folk medicine, has a neuroprotective functionin vitroand/orin vivo.In vitro, propolis significantly inhibited neurotoxicity induced in neuronally differentiated PC12 cell cultures by either 24 h hydrogen peroxide (H2O2) exposure or 48 h serum deprivation. Regarding the possible underlying mechanism, propolis protected against oxidative stress (lipid peroxidation) in mouse forebrain homogenates and scavenged free radicals [induced by diphenyl-p-picrylhydrazyl (DPPH). In micein vivo, propolis [30 or 100 mg/kg; intraperitoneally administered four times (at 2 days, 1 day and 60 min before, and at 4 h after induction of focal cerebral ischemia by permanent middle cerebral artery occlusion)] reduced brain infarction at 24 h after the occlusion. Thus, a propolis-induced inhibition of oxidative stress may be partly responsible for its neuroprotective function againstin vitrocell death andin vivofocal cerebral ischemia.

scholarly journals The Rapid Decrease in Astrocyte-Associated Dystroglycan Expression by Focal Cerebral Ischemia is Protease-Dependent

2007 ◽  
Vol 28 (4) ◽  
pp. 812-823 ◽  
Author(s):  
Richard Milner ◽  
Stephanie Hung ◽  
Xiaoyun Wang ◽  
Maria Spatz ◽  
Gregory J del Zoppo
Keyword(s):  
Cerebral Ischemia ◽  
Basal Lamina ◽  
Focal Cerebral Ischemia ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Receptor Expression ◽  
Cerebral Microvessels ◽  
The Impact

During focal cerebral ischemia, the detachment of astrocytes from the microvascular basal lamina is not completely explained by known integrin receptor expression changes. Here, the impact of experimental ischemia (oxygen—glucose deprivation (OGD)) on dystroglycan expression by murine endothelial cells and astrocytes grown on vascular matrix laminin, perlecan, or collagen and the impact of middle cerebral artery occlusion on αβ-dystroglycan within cerebral microvessels of the nonhuman primate were examined. Dystroglycan was expressed on all cerebral microvessels in cortical gray and white matter, and the striatum. Astrocyte adhesion to basal lamina proteins was managed in part by α-dystroglycan, while ischemia significantly reduced expression of dystroglycan both in vivo and in vitro. Furthermore, dystroglycan and integrin α6β4 expressions on astrocyte end-feet decreased in parallel both in vivo and in vitro. The rapid loss of astrocyte dystroglycan during OGD appears protease-dependent, involving an matrix metalloproteinase-like activity. This may explain the rapid detachment of astrocytes from the microvascular basal lamina during ischemic injury, which could contribute to significant changes in microvascular integrity.

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