alexa Deciphering the Blood-Brain Barrier Damage in Stroke: Mitochondrial Mechanism | OMICS International
E-ISSN: 2314-7326
P-ISSN: 2314-7334
Journal of Neuroinfectious Diseases
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Deciphering the Blood-Brain Barrier Damage in Stroke: Mitochondrial Mechanism

Francis Ayuka*, and Ross Barnett
Department of Physiology and Pharmacology, Experimental Stroke Core, Center for Basic and Translational Stroke Research, West Virginia University, Morgantown, West Virginia, USA
Corresponding Author : Xuefang Ren, Dr. Med.
Biomedical Research Center Rm.109
One Medical Center Dr. PO Box 9229
Morgantown, WV 26506 USA
Tel:
1-304-581-1892
E-mail: [email protected]
Received: July 18, 2015; Accepted: August 19, 2015 Published: August 22, 2015
Citation: Ren X, Simpkins JW (2015) Deciphering the Blood-Brain Barrier Damage in Stroke: Mitochondrial Mechanism. J Neuroinfect Dis S2:e002. doi:10.4172/2314-7326.S2-e002
Copyright: © 2015 Ren X, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Related article at Pubmed, Scholar Google

Visit for more related articles at Journal of Neuroinfectious Diseases

Abstract

Stroke is a complex vascular and neurological syndrome that can lead to death and disability. About 15 million people worldwide and 800,000 people in the United States suffer stroke each year . On average, in the U.S. every 40 seconds someone has a stroke and every 4 minutes someone dies from a stroke. This medical emergency has very limited treatments, and causes serious health and economic burdens in the United States and globally. Blood-brain barrier (BBB) is composed of highly specialized cerebrovascular endothelial cells, seals brain tissue from the circulating blood, and prevents blood, bacteria or toxins from reaching the central nervous system (CNS). In acute ischemic stroke, BBB is disrupted, and blood solutes penetrate into the CNS parenchymal extracellular space then cause cerebral edema . Although much has been observed in this stroke-induced brain edema, such as inflammatory infiltration, releasing of chemokines and cytokines, much less has the mechanism of BBB disruption been understood.

www.omicsonline.org/searchresult.phpIntroduction

Stroke is a complex vascular and neurological syndrome that can lead to death and disability [1]. About 15 million people worldwide [1] and 800,000 people in the United States suffer stroke each year [2]. On average, in the U.S. every 40 seconds someone has a stroke and every 4 minutes someone dies from a stroke [2]. This medical emergency has very limited treatments, and causes serious health and economic burdens in the United States and globally.

Blood-brain barrier
(BBB) is composed of highly specialized cerebrovascular endothelial cells, seals brain tissue from the circulating blood, and prevents blood, bacteria or toxins from reaching the central nervous system (CNS). In acute ischemic stroke, BBB is disrupted, and blood solutes penetrate into the CNS parenchymal extracellular space then cause cerebral edema [3]. Although much has been observed in this stroke-induced brain edema, such as inflammatory infiltration, releasing of chemokines and cytokines, much less has the mechanism of BBB disruption been understood.

Enrichment of mitochondria in the BBB capillaries has been observed 3 decades ago [4]. It has been recognized that mitochondria involve in maintaining of ion differentials and transportation of chemicals between blood and brain extracellular fluid. We have recently demonstrated that mitochondria are crucial for shaping the cerebral endothelial capillary architecture and the integrity of the BBB [5]. Mitochondrial blockade rapidly opens the BBB both in vitro cell culture model and in vivo epidural application model, increases BBB permeability, and exacerbates stroke outcomes in acute experimental stroke in mice [5].

It is estimated that 30% to 40% stroke patients had recent acute infections [6]. Post-stroke infections worsen outcomes in patients [6,7]. Infection mimic, bacteria-derived lipopolysaccharide exacerbates stroke outcomes in experimental stroke models [5,8,9]. McColl et al. [9] reported that lipopolysaccharide challenge induces inflammatory responses, activates immune cells to release of inflammatory cytokines and chemokines, which further act on vascular endothelial system and exacerbate brain damage in murine experimental stroke. However, our work reveals that lipopolysaccharide directly acts on its receptor, toll-like receptor 4 (TLR4), communicates with TLR4 signal pathways, and compromises mitochondrial oxidative phosphorylation on BBB endothelium [5]. Mitochondrial damage has also been documented in ischemic stroke patients [10,11] and experimental stroke models [12,13]. The “double attack” from stroke and infection drives endothelial mitochondria in a direction unfavorable to the functional BBB and worsens stroke outcomes.

Mitochondria participate in generation of ATP and maintenance of body temperature [14]. Is body temperature affected if the endothelial mitochondria are compromised by infections/stroke? The answer is yes. Usually, you might feel cold at first during an infection, and this hypothermia is followed by hyperthermia. Therefore, the first response to infections/stroke could be a direct mitochondrial impairment that may cause hypothermia, then the second is the induced cytokine productions (some of them are known “pyrogens”), which are well studied in infections- or stroke-induced inflammatory responses and lead to hyperthermia.

It is expected that targeting of BBB endothelial mitochondria protects BBB damage in stroke. Estrogen increases cerebrovascular expression of several mitochondrial respiratory chain proteins, including cytochrome c and complex IV subunits [15]. Estrogen has been shown to reduce BBB permeability [16] and attenuate stroke damage [17]. Mitochondrial failure is observed in the form of reduced activity of respiratory chain complex I, III and IV during post cerebral ischemia/reperfusion injury [18]. Other mitochondrial protecting drugs specifically targeting these complexes in BBB endothelium may alleviate BBB damage and improve stroke outcomes as well.

Treatments for ischemic stroke are currently limited to an FDA-approved drug, recombinant tissue plasminogen activator (tPA) within 4.5 hour therapeutic window [19]. However, tPA does not target endothelial mitochondria or inflammatory responses. Unveiling of this mitochondrial mechanism may lead to the successful development of novel therapeutic strategies aimed at endothelial mitochondria. This approach will be beneficial for the large populations of stroke patients, and other BBB involved neurological diseases.
 
References




















Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

Article Usage

  • Total views: 12041
  • [From(publication date):
    specialissue-2015 - Dec 15, 2017]
  • Breakdown by view type
  • HTML page views : 8165
  • PDF downloads : 3876
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version