Topics

Cystatin C Improves Blood-Brain Barrier Integrity After Ischemic Brain Injury in Mice.

08:00 EDT 11th October 2019 | BioPortfolio

Summary of "Cystatin C Improves Blood-Brain Barrier Integrity After Ischemic Brain Injury in Mice."

Cystatin C, a well-established biomarker of renal function, has been associated with a protective effect against stroke. However, the potential neuroprotective mechanism of cystatin C in ischemic brain injury remains unclear. Our study hypothesized that cystatin C can ameliorate blood-brain barrier (BBB) disruption by upregulating caveolin-1 expression, thereby improving neurological outcomes in cerebral ischemic injury. Western blotting, immunohistochemistry, immunofluorescence staining, and immunoprecipitation were performed to investigate target proteins. Evans Blue and gelatin zymography were used to examine the effect of cystatin C on BBB disruption. Plasmid and small interfering RNA (siRNA) transfection was used to observe alterations in caveolin-1 and occludin expression induced by changes in cystatin C expression. Intriguingly, our study showed that the expression of both cystatin C and caveolin-1 was increased in middle cerebral artery occlusion (MCAO)-injured mice, and pretreatment with exogenous cystatin C significantly increased caveolin-1 expression, reduced Evans Blue leakage in the injured brain region, and decreased the enzymatic activity of matrix metallopeptidase-9 (MMP-9). Meanwhile, our study also showed that the overexpression of cystatin C greatly enhanced caveolin-1 expression, which later increased occludin expression in oxygen-glucose deprivation (OGD)-exposed brain microvascular endothelial (bEnd.3) cells. On the other hand, the knockdown of cystatin C induced the opposite outcomes. These experimental results indicate a positive role for cystatin C in the regulation of caveolin-1 and occludin expression in cerebral ischemic injury. Taken together, these data unveil a new mechanism of the regulation of caveolin-1 expression by cystatin C in the maintenance of BBB integrity after ischemic brain injury and provide new clues for the identification of potential therapeutic strategies for stroke.

Affiliation

Journal Details

This article was published in the following journal.

Name: Journal of neurochemistry
ISSN: 1471-4159
Pages:

Links

DeepDyve research library

PubMed Articles [17455 Associated PubMed Articles listed on BioPortfolio]

Calcitriol protects the Blood-Brain Barrier integrity against ischemic stroke and reduces vasogenic brain edema via antioxidant and antiapoptotic actions in rats.

Vasogenic brain edema is the most important complication of ischemic stroke that aggravates primary brain injury. Ischemia-Reperfusion (IR)-induced Blood-Brain Barrier (BBB) impairment limits the use ...

Angioneurins-key regulators of blood-brain barrier integrity during hypoxic and ischemic brain injury.

The loss of blood-brain barrier (BBB) integrity leading to vasogenic edema and brain swelling is a common feature of hypoxic/ischemic brain diseases such as stroke, but is also central to the etiology...

Contributions of 12/15-Lipoxygenase to Bleeding in the Brain Following Ischemic Stroke.

Ischemic strokes are caused by one or more blood clots that typically obstruct one of the major arteries in the brain, but frequently also result in leakage of the blood-brain barrier and subsequent h...

Autoimmunity in acute ischemic stroke and the role of blood-brain barrier: the dark side or the light one?

This article presents a synopsis of the current data on the mechanisms of blood-brain barrier (BBB) alteration and autoimmune response in acute ischemic stroke. Most researchers confirm the relationsh...

Dl-3-N-Butylphthalide Alleviates the Blood-Brain Barrier Permeability of Focal Cerebral Ischemia Reperfusion in Mice.

Ischemic stroke occurs following arterial occlusion and subsequent blood flow cease, and restoration of blood supply by thrombolytic therapy may cause cerebral ischemic reperfusion (IR) injury resulti...

Clinical Trials [13646 Associated Clinical Trials listed on BioPortfolio]

Protective Effects of Normobaric Hyperoxia on Blood Brain Barrier in Patients With Acute Ischemic Stroke

The purpose of this study is to find out a serum marker for the evaluation of blood brain barrier damage based on animal experiments and investigate the effect of NBO(Normobaric hyperoxi...

The Relevance of the Blood-brain Barrier to Cognitive Dysfunction and Alzheimer's Disease

This study attempts to replicate the findings published in Nature Medicine by Nation and colleagues (2019). By using a large observational cohort (DZNE - Longitudinal Cognitive Impairment ...

The Effect of Alemtuzumab on the Blood-brain-barrier and the Brain's Metabolism in Multiple Sclerosis Patients

The development and progression of multiple sclerosis seem to be driven by concomitant inflammation and, to a less well-defined degree, disturbances in metabolism of individual cells of th...

Measuring Blood Flow Characteristics Using Dynamic Contrast Enhanced Magnetic Resonance Imaging

Dynamic contrast-enhanced (DCE) MRI gives quantitative and semi-quantitative information about the integrity of the vascular system and can be used to quantify blood-brain barrier (BBB) in...

ExAblate Blood-Brain Barrier Opening for Treatment of Alzheimer's Disease

The purpose of this study is to evaluate the safety and efficacy of the ExAblate® Model 4000 Type 2.0 system as a tool to open the blood-brain barrier (BBB) in patients with probable Alzh...

Medical and Biotech [MESH] Definitions

The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.

The barrier between the perineurium of PERIPHERAL NERVES and the endothelium (ENDOTHELIUM, VASCULAR) of endoneurial CAPILLARIES. The perineurium acts as a diffusion barrier, but ion permeability at the blood-nerve barrier is still higher than at the BLOOD-BRAIN BARRIER.

Measurement of light given off by fluorescein in order to assess the integrity of various ocular barriers. The method is used to investigate the blood-aqueous barrier, blood-retinal barrier, aqueous flow measurements, corneal endothelial permeability, and tear flow dynamics.

Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.

A claudin subtype that is found localized to TIGHT JUNCTIONS in VASCULAR ENDOTHELIAL CELLS. The protein was initially identified as one of several proteins which are deleted in VELOCARDIOFACIAL SYNDROME and may play an important role in maintaining the integrity of the BLOOD-BRAIN BARRIER.

Quick Search


DeepDyve research library

Relevant Topics

Nephrology - kidney function
Nephrology is a specialty of medicine and pediatrics that concerns itself with the study of normal kidney function, kidney problems, the treatment of kidney problems and renal replacement therapy (dialysis and kidney transplantation). Systemic conditions...

Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...


Searches Linking to this Article