Candesartan has been reported to have a protective effect on cerebral ischemia in vivo and in human ischemic stroke. We studied the direct effects of candesartan on blood-brain barrier (BBB) function with our in vitro monolayer model generated using rat brain capillary endothelial cells (RBECs). The in vitro BBB model was subjected to normoxia or 6-h oxygen glucose deprivation (OGD)/24-h reoxygenation, with or without candesartan. 6-h OGD/24-h reoxygenation decreased transendothelial electrical resistance and increased the endothelial permeability for sodium fluorescein in RBEC monolayers. Candesartan (10 nM) improved RBEC barrier dysfunction induced by 6-h OGD/24-h reoxygenation. Immunostaining and immunoblotting analysis indicated that the effect of candesartan on barrier function under 6-h OGD/24-h reoxygenation was not related to the expression levels of tight junction proteins. However, candesartan affected RBEC morphological changes induced by 6-h OGD/24-h reoxygenation. We analyzed oxidative stress and cell viability using chemical reagents. Candesartan improved cell viability following 6-h OGD/24-h reoxygenation, whereas candesartan had no effect on oxidative stress. These results show that candesartan directly improves cell function and viability of brain capillary endothelial cells under OGD/reoxygenation, suggesting that the protective effects of candesartan on ischemic stroke are related to protection of the BBB.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s10571-014-0152-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
cPKCγ Inhibits Caspase-9-Initiated Neuronal Apoptosis in an Ischemia Reperfusion Model In Vitro Through p38 MAPK-p90RSK-Bad Pathway.
Neurochem Res
February 2023
The Second Clinical Medical College, Lanzhou University Second Hospital, No. 82 Cuiyingmen Street, Chengguan District, Lanzhou, 730030, Gansu, China.
Strokes are one of the leading causes of death and disability in the world. Previously we have found that conventional protein kinase Cγ (cPKCγ) plays neuroprotective role in ischemic strokes. Further, we found that cPKCγ knockdown increased the level of cleaved (cl)-Caspase-3.
View Article and Find Full Text PDFEffects of fasudil on blood-brain barrier integrity.
Fluids Barriers CNS
June 2022
Department of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Background: Cerebral infarction accounts for 85% of all stroke cases. Even in an era of rapid and effective recanalization using an intravascular approach, the majority of patients have poor functional outcomes. Thus, there is an urgent need for the development of therapeutic agents to treat acute ischemic stroke.
View Article and Find Full Text PDFDownregulation of mitochondrial pyruvate carrier 2 aggravates neuronal injury in the cortex following cerebral ischemia in rat.
Brain Res Bull
July 2022
Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China. Electronic address:
Cerebral ischemia is one of the most common disabling and lethal diseases worldwide, but its underlying mechanisms remain unclear. Mitochondrial pyruvate carrier 2 (MPC2), a subunit of MPC complex, plays pivotal roles in coordinating glycolytic and mitochondrial activities. In the present study, the expression of MPC2 was significantly reduced in the ischemic cerebral cortex of rats at 24 h after bilateral internal carotid artery occlusion (BICAO), and in the cortical neurons after 1 h oxygen-glucose deprivation (OGD)/24 h reoxygenation treatment.
View Article and Find Full Text PDFcPKCγ alleviates ischemic injury through modulating synapsin Ia/b phosphorylation in neurons of mice.
Brain Res Bull
September 2018
Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, PR China. Electronic address:
Conventional protein kinase C (cPKC)γ and synapsin Ia/b have been implicated in the development of ischemic stroke, but their relationships and functions are unclear. In the present study, the oxygen-glucose deprivation (OGD)-induced ischemic insult in primary cultured cortical neurons in vitro and middle cerebral artery occlusion (MCAO)-induced ischemic stroke model in vivo were used to elucidate the function of cPKCγ and its modulation on synapsin Ia/b phosphorylation in ischemic stroke. We found that cPKCγ knockout significantly increased the infarct volume of mice after 1 h MCAO/72 h reperfusion by using triphenyltetrazolium chloride (TTC) staining.
View Article and Find Full Text PDFIdentification of IL-17A-derived neural cell type and dynamic changes of IL-17A in serum/CSF of mice with ischemic stroke.
Neurol Res
June 2017
b Department of Neurobiology and Center of Stroke , Beijing Institute for Brain Disorders, Capital Medical University, Beijing , PR China.
Background: Interleukin (IL)-17A was reported to be involved in the development of post-ischemic stroke inflammatory response and functional recovery. However, the IL-17A dynamic changes in serum/cerebrospinal fluid (CSF) and its role in neuronal injury following ischemic stroke are unclear.
Methods: In vivo ischemic stroke was induced by 1 h of middle cerebral artery occlusion (MCAO) and 6 h-7 d reperfusion (R) in mice, while in vitro stroke was induced by 1 h oxygen-glucose deprivation (OGD)/24 h reoxygenation (R) in cultured cortical neurons.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!