E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Blood–Brain Barrier in CNS Injury and Repair"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 July 2017)

Special Issue Editors

Guest Editor
Prof. Dr. Hari Shanker Sharma

Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
Website | E-Mail
Interests: blood–brain barrier; brain edema; neurochemistry; neurophysiology; neuropathology; nanoneuroscience; nanoneuropharmacology; neuroregeneration; central nervous system injury; traumatic brain injury; neurorepair; military medicine; Alzheimer’s disease; Parkinson’s disease; neurotrophic factors
Guest Editor
Dr. Aruna Sharma

Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
Website | E-Mail
Interests: military medicine; high altitude brain pathology; blood–brain barrier; nanodrug delivery; stem cells; neuroregeneration; nanowired drug delivery; neurodegeneration; neuroregeneration; behavioural physiology; neurochemistry; Alzheimer’s disease; Parkinson’s disease; brain pathology; neurorepair

Special Issue Information

Dear Colleagues,

The blood–brain barrier (BBB) regulates the fluid environment of the brain strictly within a narrow limit. The BBB is anatomically positioned within the endothelial cells of the cerebral capillaries that are connected with tight junctions. Thus, passage of substances, drugs, proteins and other large molecules are severely restricted at the BBB. However, all kinds of brain diseases following trauma, ischemia, strenuous stress, psychiatric illnesses and/or psychostimulants overuse, etc., are associated with breakdown of the BBB to large molecules, e.g., proteins. Also, several neurological diseases, e.g., Alzheimer’s, Parkinson’s, Huntington’s disease as well as amyotrophic lateral sclerosis, neuropathic pain, liver cirrhosis, hypertension and/or diabetes and related chronic disorders are associated with breakdown of the BBB. BBB breakdown allows passage of serum proteins and other toxins into the fluid microenvironment of the central nervous system (CNS) resulting in cerebral edema formation and subsequent cellular injuries. Interestingly, no suitable therapeutic strategies have yet been worked out to treat such neurological diseases. This Special Issue will present new developments in the field of BBB research to improve current therapeutic measures as well as provide a platform to discuss the use of nanomedicine in several CNS diseases for the benefit of mankind. We ask experts in the field to contribute their latest research, perspectives, or reviews on this fascinating and rapidly progressing topic.

Prof. Dr. Hari Shanker Sharma
Dr. Aruna Sharma
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Blood–brain barrier
  • Brain edema
  • Neurodegeneration
  • Neurorepair
  • Cerebral blood flow
  • Blood–spinal cord barrier
  • Blood–CSF-barrier
  • Alzheimer’s disease
  • Parkinson’s disease
  • Psychostimulants
  • Brain pathology
  • Nanomedicine

Published Papers (6 papers)

View options order results:
result details:
Displaying articles 1-6
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Chrysin Attenuates VCAM-1 Expression and Monocyte Adhesion in Lipopolysaccharide-Stimulated Brain Endothelial Cells by Preventing NF-κB Signaling
Int. J. Mol. Sci. 2017, 18(7), 1424; doi:10.3390/ijms18071424
Received: 30 May 2017 / Revised: 22 June 2017 / Accepted: 27 June 2017 / Published: 3 July 2017
PDF Full-text (3313 KB) | HTML Full-text | XML Full-text
Abstract
Adhesion of leukocytes to endothelial cells plays an important role in neuroinflammation. Therefore, suppression of the expression of adhesion molecules in brain endothelial cells may inhibit neuroinflammation. Chrysin (5,7-dihydroxyflavone) is a flavonoid component of propolis, blue passion flowers, and fruits. In the present
[...] Read more.
Adhesion of leukocytes to endothelial cells plays an important role in neuroinflammation. Therefore, suppression of the expression of adhesion molecules in brain endothelial cells may inhibit neuroinflammation. Chrysin (5,7-dihydroxyflavone) is a flavonoid component of propolis, blue passion flowers, and fruits. In the present study, we examined the effects of chrysin on lipopolysaccharide (LPS)-induced expression of vascular cell adhesion molecule-1 (VCAM-1) in mouse cerebral vascular endothelial (bEnd.3) cells. In bEnd.3 cells, LPS increased mRNA expression of VCAM-1 in a time-dependent manner, and chrysin significantly decreased LPS-induced mRNA expression of VCAM-1. Chrysin also reduced VCAM-1 protein expression in a concentration-dependent manner. Furthermore, chrysin blocked adhesion of monocytes to bEnd.3 cells exposed to LPS. Nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase, which are all activated by LPS, were significantly inhibited by chrysin. These results indicate that chrysin inhibits the expression of VCAM-1 in brain endothelial cells by inhibiting NF-κB translocation and MAPK signaling, resulting in the attenuation of leukocyte adhesion to endothelial cells. The anti-inflammatory effects of chrysin suggest a possible therapeutic application of this agent to neurodegenerative diseases, such as multiple sclerosis, septic encephalopathy, and allergic encephalomyelitis. Full article
(This article belongs to the Special Issue Blood–Brain Barrier in CNS Injury and Repair)
Figures

Open AccessArticle PAMAM Dendrimers Cross the Blood–Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice
Int. J. Mol. Sci. 2017, 18(3), 628; doi:10.3390/ijms18030628
Received: 21 February 2017 / Revised: 10 March 2017 / Accepted: 10 March 2017 / Published: 14 March 2017
Cited by 1 | PDF Full-text (7056 KB) | HTML Full-text | XML Full-text
Abstract
Drug delivery into the central nervous system (CNS) is challenging due to the blood–brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the
[...] Read more.
Drug delivery into the central nervous system (CNS) is challenging due to the blood–brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the present study investigates the role of novel mixed surface dendrimers, which have potentially less toxicity and can cross the BBB when administered through the carotid artery in mice. In vitro experiments investigated the uptake of amine dendrimers (G1-NH2 and G4-NH2) and novel dendrimers (G1-90/10 and G4-90/10) by primary cortical cultures. In vivo experiments involved transplantation of G4-90/10 into mice through (1) invasive intracranial injections into the striatum; and (2) less invasive carotid injections. The animals were sacrificed 24-h and 1-week post-transplantations and their brains were analyzed. In vivo experiments proved that the G4-90/10 can cross the BBB when injected through the carotid artery and localize within neurons and glial cells. The dendrimers were found to migrate through the corpus callosum 1-week post intracranial injection. Immunohistochemistry showed that the migrating cells are the dendrimer-infected glial cells. Overall, our results suggest that poly-amidoamine (PAMAM) dendrimers may be used as a minimally invasive means to deliver biomolecules for treating neurological diseases or disorders Full article
(This article belongs to the Special Issue Blood–Brain Barrier in CNS Injury and Repair)
Figures

Open AccessArticle Monitoring the Response of Hyperbilirubinemia in the Mouse Brain by In Vivo Bioluminescence Imaging
Int. J. Mol. Sci. 2017, 18(1), 50; doi:10.3390/ijms18010050
Received: 23 November 2016 / Revised: 18 December 2016 / Accepted: 22 December 2016 / Published: 28 December 2016
PDF Full-text (3203 KB) | HTML Full-text | XML Full-text
Abstract
Increased levels of unconjugated bilirubin are neurotoxic, but the mechanism leading to neurological damage has not been completely elucidated. Innovative strategies of investigation are needed to more precisely define this pathological process. By longitudinal in vivo bioluminescence imaging, we noninvasively visualized the brain
[...] Read more.
Increased levels of unconjugated bilirubin are neurotoxic, but the mechanism leading to neurological damage has not been completely elucidated. Innovative strategies of investigation are needed to more precisely define this pathological process. By longitudinal in vivo bioluminescence imaging, we noninvasively visualized the brain response to hyperbilirubinemia in the MITO-Luc mouse, in which light emission is restricted to the regions of active cell proliferation. We assessed that acute hyperbilirubinemia promotes bioluminescence in the brain region, indicating an increment in the cell proliferation rate. Immunohistochemical detection in brain sections of cells positive for both luciferase and the microglial marker allograft inflammatory factor 1 suggests proliferation of microglial cells. In addition, we demonstrated that brain induction of bioluminescence was altered by pharmacological displacement of bilirubin from its albumin binding sites and by modulation of the blood–brain barrier permeability, all pivotal factors in the development of bilirubin-induced neurologic dysfunction. We also determined that treatment with minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, or administration of bevacizumab, an anti-vascular endothelial growth factor antibody, blunts bilirubin-induced bioluminescence. Overall the study supports the use of the MITO-Luc mouse as a valuable tool for the rapid response monitoring of drugs aiming at preventing acute bilirubin-induced neurological dysfunction. Full article
(This article belongs to the Special Issue Blood–Brain Barrier in CNS Injury and Repair)
Figures

Review

Jump to: Research

Open AccessReview Blood-Brain Barrier Dysfunction and the Pathogenesis of Alzheimer’s Disease
Int. J. Mol. Sci. 2017, 18(9), 1965; doi:10.3390/ijms18091965
Received: 25 August 2017 / Revised: 6 September 2017 / Accepted: 7 September 2017 / Published: 13 September 2017
PDF Full-text (1684 KB) | HTML Full-text | XML Full-text
Abstract
Brain capillary endothelial cells form the blood-brain barrier (BBB), which is covered with basement membranes and is also surrounded by pericytes and astrocyte end-feet in the neurovascular unit. The BBB tightly regulates the molecular exchange between the blood flow and brain parenchyma, thereby
[...] Read more.
Brain capillary endothelial cells form the blood-brain barrier (BBB), which is covered with basement membranes and is also surrounded by pericytes and astrocyte end-feet in the neurovascular unit. The BBB tightly regulates the molecular exchange between the blood flow and brain parenchyma, thereby regulating the homeostasis of the central nervous system (CNS). Thus, dysfunction of the BBB is likely involved in the pathogenesis of several neurological diseases, including Alzheimer’s disease (AD). While amyloid-β (Aβ) deposition and neurofibrillary tangle formation in the brain are central pathological hallmarks in AD, cerebrovascular lesions and BBB alteration have also been shown to frequently coexist. Although further clinical studies should clarify whether BBB disruption is a specific feature of AD pathogenesis, increasing evidence indicates that each component of the neurovascular unit is significantly affected in the presence of AD-related pathologies in animal models and human patients. Conversely, since some portions of Aβ are eliminated along the neurovascular unit and across the BBB, disturbing the pathways may result in exacerbated Aβ accumulation in the brain. Thus, current evidence suggests that BBB dysfunction may causatively and consequently contribute to AD pathogenesis, forming a vicious cycle between brain Aβ accumulation and neurovascular unit impairments during disease progression. Full article
(This article belongs to the Special Issue Blood–Brain Barrier in CNS Injury and Repair)
Figures

Open AccessReview The Role of Neurogenic Inflammation in Blood-Brain Barrier Disruption and Development of Cerebral Oedema Following Acute Central Nervous System (CNS) Injury
Int. J. Mol. Sci. 2017, 18(8), 1788; doi:10.3390/ijms18081788
Received: 18 July 2017 / Revised: 7 August 2017 / Accepted: 15 August 2017 / Published: 17 August 2017
Cited by 1 | PDF Full-text (1362 KB) | HTML Full-text | XML Full-text
Abstract
Acute central nervous system (CNS) injury, encompassing traumatic brain injury (TBI) and stroke, accounts for a significant burden of morbidity and mortality worldwide, largely attributable to the development of cerebral oedema and elevated intracranial pressure (ICP). Despite this, clinical treatments are limited and
[...] Read more.
Acute central nervous system (CNS) injury, encompassing traumatic brain injury (TBI) and stroke, accounts for a significant burden of morbidity and mortality worldwide, largely attributable to the development of cerebral oedema and elevated intracranial pressure (ICP). Despite this, clinical treatments are limited and new therapies are urgently required to improve patient outcomes and survival. Originally characterised in peripheral tissues, such as the skin and lungs as a neurally-elicited inflammatory process that contributes to increased microvascular permeability and tissue swelling, neurogenic inflammation has now been described in acute injury to the brain where it may play a key role in the secondary injury cascades that evolve following both TBI and stroke. In particular, release of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) appear to be critically involved. In particular, increased SP expression is observed in perivascular tissue following acute CNS injury, with the magnitude of SP release being related to both the frequency and degree of the insult. SP release is associated with profound blood-brain barrier disruption and the subsequent development of vasogenic oedema, as well as neuronal injury and poor functional outcomes. Inhibition of SP through use of a neurokinin 1 (NK1) antagonist is highly beneficial following both TBI and ischaemic stroke in pre-clinical models. The role of CGRP is more unclear, especially with respect to TBI, with both elevations and reductions in CGRP levels reported following trauma. However, a beneficial role has been delineated in stroke, given its potent vasodilatory effects. Thus, modulating neuropeptides represents a novel therapeutic target in the treatment of cerebral oedema following acute CNS injury. Full article
(This article belongs to the Special Issue Blood–Brain Barrier in CNS Injury and Repair)
Figures

Figure 1

Open AccessReview Finding a Balance between Protection and Pathology: The Dual Role of Perforin in Human Disease
Int. J. Mol. Sci. 2017, 18(8), 1608; doi:10.3390/ijms18081608
Received: 14 June 2017 / Revised: 20 July 2017 / Accepted: 20 July 2017 / Published: 25 July 2017
PDF Full-text (3852 KB) | HTML Full-text | XML Full-text
Abstract
Perforin is critical for controlling viral infection and tumor surveillance. Clinically, mutations in perforin are viewed as unfavorable, as lack of this pore-forming protein results in lethal, childhood disease, familial hemophagocytic lymphohistiocytosis type 2 (FHL 2). However, many mutations in the coding region
[...] Read more.
Perforin is critical for controlling viral infection and tumor surveillance. Clinically, mutations in perforin are viewed as unfavorable, as lack of this pore-forming protein results in lethal, childhood disease, familial hemophagocytic lymphohistiocytosis type 2 (FHL 2). However, many mutations in the coding region of PRF1 are not yet associated with disease. Animal models of viral-associated blood–brain barrier (BBB) disruption and experimental cerebral malaria (ECM) have identified perforin as critical for inducing pathologic central nervous system CNS vascular permeability. This review focuses on the role of perforin in both protecting and promoting human disease. It concludes with a novel hypothesis that diversity observed in the PRF1 gene may be an example of selective advantage that protects an individual from perforin-mediated pathology, such as BBB disruption. Full article
(This article belongs to the Special Issue Blood–Brain Barrier in CNS Injury and Repair)
Figures

Figure 1

Back to Top