The vascular neural network—a new paradigm in stroke pathophysiology

Zhang, Junyi; Badaut, Jérôme; Tang, Jiping; Obenaus, André; Hartman, Richard E.; Pearce, William J.

doi:10.1038/nrneurol.2012.210

Cited by 180 publications

(175 citation statements)

References 30 publications

Supporting

Mentioning

172

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, due to the complex nature of brain structure and function, as evidenced by the neurovascular unit and vascular neural network (Lo et al, 2003; Zhang et al, 2012), further investigation is also needed to explore the interaction or cross-link of ncRNAs between the cerebrovascular endothelium and other neural cells (pericytes, astrocytes, neurons, oligodendrocytes, microglia, etc.) as an integrative ncRNA regulatory network in ischemic brain injury.…”

Section: Future Prospects For Endothelial Ncrna Studies In Cerebromentioning

confidence: 99%

Non-coding RNAs in cerebral endothelial pathophysiology: Emerging roles in stroke

Yin

Hamblin

Chen

2014

Neurochemistry International

View full text Add to dashboard Cite

Cerebral vascular endothelial cells form the major element of the blood-brain barrier (BBB) and constitute the primary interface between circulating blood and brain parenchyma. The structural and functional changes in cerebral endothelium during cerebral ischemia are well known to result in BBB disruption, vascular inflammation, edema, and angiogenesis. These complex pathological processes directly contribute to brain infarction, neurological deficits, and post-stroke neurovascular remodeling. Ischemic endothelial dysfunction appears to be tightly controlled by multiple gene signaling networks. Non-coding RNAs (ncRNAs) are functional RNA molecules that are generally not translated into proteins but can actively regulate the expression and function of many thousands of protein-coding genes by different mechanisms. Various classes of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), small nucleolar RNAs (snoRNAs) and piwi-interacting RNAs (piRNAs), are highly expressed in the cerebrovascular endothelium where they serve as critical mediators to maintain normal cerebral vascular functions. Dysregulation of ncRNA activities has been closely linked to the pathophysiology of cerebral vascular endothelium and neurologic functional disorders in the brain’s response to ischemic stimuli. In this review, we summarize recent advancements of these ncRNA mediators in the brain vasculature, highlighting the specific roles of endothelial miRNAs in stroke.

show abstract

Section: Future Prospects For Endothelial Ncrna Studies In Cerebromentioning

confidence: 99%

Non-coding RNAs in cerebral endothelial pathophysiology: Emerging roles in stroke

Yin

Hamblin

Chen

2014

Neurochemistry International

View full text Add to dashboard Cite

show abstract

“…There have been prior reports of sustained-release formulations of dihydropyridines and other drugs administered into the subarachnoid space for SAH [12,13,29,30]. While there has been some evidence that these may be effective, these formulations have had limitations, including lack of characterization of pharmacokinetics, stability, and injectability, use of materials with known or unknown toxicity, and limited data on efficacy of the active drug.…”

Section: Discussionmentioning

confidence: 99%

A Site-Specific, Sustained-Release Drug Delivery System for Aneurysmal Subarachnoid Hemorrhage

et al. 2016

View full text Add to dashboard Cite

Nimodipine is the only drug approved for use by the Food and Drug Administration for improving outcome after aneurysmal subarachnoid hemorrhage (SAH). It has less than optimal efficacy, causes dose-limiting hypotension in a substantial proportion of patients, and is administered enterally 6 times daily. We describe development of site-specific, sustainedrelease nimodipine microparticles that can be delivered once directly into the subarachnoid space or cerebral ventricles for potential improvement in outcome of patients with aneurysmal SAH. Eight injectable microparticle formulations of nimodipine in poly(DL-lactide-co-glycolide) (PLGA) polymers of varying composition were tested in vitro, and 1 was advanced into preclinical studies and clinical application. Intracisternal or intraventricular injection of nimodipine-PLGA microparticles in rats and beagles demonstrated dose-dependent, sustained concentrations of nimodipine in plasma and cerebrospinal fluid for up to 29 days with minimal toxicity in the brain or systemic tissues at doses <2 mg in rats and 51 mg in beagles, which would be equivalent of up to 612-1200 mg in humans, based on scaling relative to cerebrospinal fluid volumes. Efficacy was tested in the double-hemorrhage dog model of SAH. Nimodipine-PLGA microparticles significantly attenuated angiographic vasospasm. This therapeutic approach shows promise for improving outcome after SAH and may have broader applicability for similar diseases that are confined to body cavities or spaces, are self-limited, and lack effective treatments.

show abstract

“…The pathophysiology of subarachnoid hemorrhage (SAH) and other stroke events involve the cerebral vascular neural network which includes arterial and venous systems as well as neuronal cells and other support cells and matrix 1 . Within this vascular neural network, blood-brain barrier (BBB) damage contributes to brain edema after SAH 2 .…”

Section: Introductionmentioning

confidence: 99%

Norrin Protected Blood–Brain Barrier Via Frizzled-4/β-Catenin Pathway After Subarachnoid Hemorrhage in Rats

Chen

Zhang

Tang

et al. 2015

Stroke

Self Cite

View full text Add to dashboard Cite

Background and Purpose Norrin and its receptor Frizzled 4 have important roles in the blood-brain barrier (BBB) development. This study is to investigate a potential role and mechanism of Norrin/Frizzled 4 on protecting BBB integrity after subarachnoid hemorrhage (SAH). Methods One hundred and seventy-eight male Sprague-Dawley rats were used. SAH model was induced by endovascular perforation. Frizzled 4 small interfering RNA (siRNA) was injected intracerebroventricularly 48 hours before SAH. Norrin was administrated intracerebroventricularly 3 hours after SAH. SAH grade, neurologic scores, brain water content, Evans blue extravasation, western blots and immunofluorescence were employed to study the mechanisms of Norrin and its receptor regulation protein TSPAN12, as well as neurological outcome. Results Endogenous Norrin and TSPAN12 expression were increased after SAH, and Norrin was colocalizated with astrocytes marker GFAP in cortex. Exogenous Norrin treatment significantly alleviated neurobehavioral dysfunction, reduced brain water content and Evans blue extravasation, promoted β-catenin nuclear translocation and increased Occludin, VE-Cadherin and ZO-1 expressions. These effects were abolished by Frizzled 4 siRNA pretreated before SAH. Conclusions Norrin protected BBB integrity and improved neurological outcome after SAH, and the action of Norrin seemed mediated by Frizzled 4 receptor activation which promoted β-catenin nuclear translocation, which then enhanced Occludin, VE-Cadherin and ZO-1 expression. Norrin might have potential to protect BBB after SAH.

show abstract

The vascular neural network—a new paradigm in stroke pathophysiology

Cited by 180 publications

References 30 publications

Non-coding RNAs in cerebral endothelial pathophysiology: Emerging roles in stroke

Non-coding RNAs in cerebral endothelial pathophysiology: Emerging roles in stroke

A Site-Specific, Sustained-Release Drug Delivery System for Aneurysmal Subarachnoid Hemorrhage

Norrin Protected Blood–Brain Barrier Via Frizzled-4/β-Catenin Pathway After Subarachnoid Hemorrhage in Rats

Contact Info

Product

Resources

About