Ontogeny of tight junction protein expression in the ovine cerebral cortex during development

Sadowska, Grazyna B.; Ahmedli, Nigar; Chen, Xiaodi; Stonestreet, Barbara S.

doi:10.1016/j.neuroscience.2015.09.062

Cited by 5 publications

(5 citation statements)

References 61 publications

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“…The experimental autoradiographic integrated optical density (IOD) values were expressed as a ratio to the internal control and enabled normalized comparisons among the groups. This methodology correlates well with values that were normalized as ratios to β‐actin and vinculin (Kim et al, ; Sadowska et al, ). Each immunoblot included samples from the four groups and three internal control samples.…”

Section: Methodsmentioning

confidence: 55%

Ischemia reduces inter‐alpha inhibitor proteins in the brain of the ovine fetus

Spasova

Chen

Sadowska

et al. 2016

Developmental Neurobiology

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Hypoxic-ischemic (HI) brain injury is a major cause of neurological abnormalities in the perinatal period. Inflammation contributes to the evolution of HI brain injury. Inter-alpha inhibitor proteins (IAIPs) are a family of proteins that are part of the innate immune system. We have reported that endogenous IAIPs exhibit developmental changes in ovine brain and that exogenous IAIP treatment reduces neuronal death in HI neonatal rats. However, the effects of HI on endogenous IAIPs in brain have not been previously examined. In this study, we examined the effects of ischemia-reperfusion on endogenous IAIPs levels in fetal sheep brain. Cerebral cortex, cerebellum, cervical spinal cord, choroid plexus, and CSF were snap frozen from sham control fetuses at 127 days gestation and after 30-min of carotid occlusion and 4-, 24-, and 48-hours of reperfusion. IAIP levels were determined by Western immunoblot. IAIP expressions of the 250 kDa Inter-alpha inhibitor (IaI) and 125 kDa Pre-alpha inhibitor (PaI) in cerebral cortex and PaI in cerebellum were reduced (P<0.05) 4-hours after ischemia compared with controls and returned toward control levels 24- and 48-hours after ischemia. CSF PaI and IaI were reduced 48 hours after ischemia. We conclude that IAIPs in cerebral cortex and cerebellum are reduced by brain ischemia, and return toward control levels between 24 and 48 hours after ischemia. However, changes in CSF IAIPs were delayed, exhibiting decreases 48 hours after ischemia. We speculate that the decreases in endogenous IAIPs reflect increased utilization, potentially suggesting that they have endogenous neuroprotective properties.

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Section: Methodsmentioning

confidence: 55%

Ischemia reduces inter‐alpha inhibitor proteins in the brain of the ovine fetus

Spasova

Chen

Sadowska

et al. 2016

Developmental Neurobiology

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“…TJ proteins are major structural proteins in both endothelial cells of the BBB and ependymal cells of blood–CSF barriers ( Sadowska et al, 2015 ). Within the CNS vasculature, the BBB is localized at the interface between the blood and cerebral tissue and is composed of endothelial cells connected by an extensive network of complex TJ and adherens junction (AJ) proteins, which influence junction organization at the BBB.…”

Section: Discussionmentioning

confidence: 99%

S1PR3, as a Core Protein Related to Ischemic Stroke, is Involved in the Regulation of Blood–Brain Barrier Damage

Fan

Chen

et al. 2022

Front. Pharmacol.

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Background: Ischemic stroke is the most common stroke incident. Sphingosine-1-phosphate (S1P) receptor 3 (S1PR3) is a member of the downstream G protein-coupled receptor family of S1P. The effect of S1PR3 on ischemic stroke remains elusive.Methods: We downloaded two middle cerebral artery occlusion (MCAO) microarray datasets from the Gene Expression Omnibus (GEO) database and screened differentially expressed genes (DEGs). Then, we performed a weighted gene coexpression network analysis (WGCNA) and identified the core module genes related to ischemic stroke. We constructed a protein–protein interaction (PPI) network for the core genes in which DEGs and WGCNA intersected. Finally, we discovered that S1PR3 was involved as the main member of the red proteome. Then, we explored the mechanism of S1PR3 in the mouse tMCAO model. The S1PR3-specific inhibitor CAY10444 was injected into the abdominal cavity of mice after cerebral ischemia/reperfusion (I/R) injury, and changes in the expression of blood–brain barrier-related molecules were measured using PCR, western blotting, and immunofluorescence staining.Results: Both GEO datasets showed that S1PR3 was upregulated during cerebral I/R in mice. WGCNA revealed that the light yellow module had the strongest correlation with the occurrence of IS. We determined the overlap with DEGs, identified 146 core genes that are potentially related to IS, and constructed a PPI network. Finally, S1PR3 was found to be the main member of the red proteome. In the mouse cerebral I/R model, S1PR3 expression increased 24 h after ischemia. After the administration of CAY10444, brain edema and neurological deficits in mice were ameliorated. CAY10444 rescued the decreased expression of the tight junction (TJ) proteins zonula occludens 1 (ZO1) and occludin after ischemia induced by transient MCAO (tMCAO) and reduced the increase in aquaporin 4 (AQP4) levels after tMCAO, preserving the integrity of the BBB. Finally, we found that S1PR3 is involved in regulating the mitogen-activated protein kinase (MAPK) and (phosphatidylinositol-3 kinase/serine-threonine kinase) PI3K-Akt signaling pathways.Conclusion: S1PR3 participates in the regulation of blood–brain barrier damage after cerebral I/R. S1PR3 is expected to be an indicator and predictor of cerebral ischemia, and drugs targeting S1PR3 may also provide new ideas for clinical medications.

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“…From these, claudin-5 is the most abundant in more than 500-fold greater than the other claudin subtypes (Ohtsuki, Yamaguchi et al 2008, Daneman, Zhou et al 2010, Luo, Xiao et al 2011), while claudins -1, -3 and -12 have a lower but inducible expression (Liebner, Corada et al 2008, Sadowska, Ahmedli et al 2015). …”

Section: Flux Across the Ibrbmentioning

confidence: 99%