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Blood-Brain Barrier in CNS Injury and Repair, Volume 2

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 (24 June 2019) | Viewed by 25944

Special Issue Editors

Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, 751 85 Uppsala, Sweden
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
Special Issues, Collections and Topics in MDPI journals
Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, 751 85 Uppsala, Sweden
Interests: military medicine; high altitude brain pathology; blood–brain barrier; nanodrug delivery; stem cells; neuroregeneration; nanowired drug delivery; neurodegeneration; behavioural physiology; neurochemistry; Alzheimer’s disease; Parkinson’s disease; brain pathology; neurorepair
Special Issues, Collections and Topics in MDPI journals

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

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Keywords

  • Bloodbrain barrier
  • Brain edema
  • Neurodegeneration
  • Neurorepair
  • Cerebral blood flow
  • Bloodspinal cord barrier
  • BloodCSF-barrier
  • Alzheimer’s disease
  • Parkinson’s disease
  • Psychostimulants
  • Brain pathology
  • Nanomedicine

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Published Papers (4 papers)

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Research

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17 pages, 7853 KiB  
Article
Increased Expression of Vascular Endothelial Growth Factor-D Following Brain Injury
by Sukriti Nag, Janet Manias, James H. Eubanks and Duncan J. Stewart
Int. J. Mol. Sci. 2019, 20(7), 1594; https://doi.org/10.3390/ijms20071594 - 30 Mar 2019
Cited by 18 | Viewed by 3676
Abstract
Alterations in the expression of the vascular endothelial growth factors (VEGF) A and B occur during blood–brain barrier (BBB) breakdown and angiogenesis following brain injury. In this study, the temporal and spatial expression of VEGF-D and VEGF receptors-2 and -3 (VEGFR-2 and VEGFR-3, [...] Read more.
Alterations in the expression of the vascular endothelial growth factors (VEGF) A and B occur during blood–brain barrier (BBB) breakdown and angiogenesis following brain injury. In this study, the temporal and spatial expression of VEGF-D and VEGF receptors-2 and -3 (VEGFR-2 and VEGFR-3, respectively) was determined at the mRNA and protein level in the rat cortical cold-injury model over a period of 0.5 to 6 days post-injury. In order to relate endothelial VEGF-D protein expression with BBB breakdown, dual labeling immunofluorescence was performed using antibodies to VEGF-D and to fibronectin, a marker of BBB breakdown. In control rats, VEGF-D signal was only observed in scattered perivascular macrophages in the cerebral cortex. The upregulation of VEGF-D mRNA expression was observed in the injury site between days 0.5 to 4, coinciding with the period of BBB breakdown and angiogenesis. At the protein level, intracerebral vessels with BBB breakdown to fibronectin in the lesion on days 0.5 to 4 failed to show endothelial VEGF-D. Between days 0.5 to 6, an increased VEGF-D immunoreactivity was noted in the endothelium of pial vessels overlying the lesion site, in neutrophils, macrophages, and free endothelial cells within the lesion. The upregulation of VEGFR-2 and -3 mRNA and protein expression was observed early post-injury on day 0.5. Although there was concurrent expression of VEGF-A, VEGF-B, and VEGF-D post-injury, differences in their spatial expression during BBB breakdown and angiogenesis suggest that they have specific and separate roles in these processes. Full article
(This article belongs to the Special Issue Blood-Brain Barrier in CNS Injury and Repair, Volume 2)
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10 pages, 2674 KiB  
Communication
The Influence of Capsaicin on the Integrity of Microvascular Endothelial Cell Monolayers
by Mathias Kaiser, Malgorzata Burek, Stefan Britz, Frauke Lankamp, Steffi Ketelhut, Björn Kemper, Carola Förster, Christian Gorzelanny and Francisco M. Goycoolea
Int. J. Mol. Sci. 2019, 20(1), 122; https://doi.org/10.3390/ijms20010122 - 30 Dec 2018
Cited by 13 | Viewed by 4510
Abstract
Microvascular endothelial cells are an essential part of many biological barriers, such as the blood–brain barrier (BBB) and the endothelium of the arteries and veins. A reversible opening strategy to increase the permeability of drugs across the BBB could lead to improved therapies [...] Read more.
Microvascular endothelial cells are an essential part of many biological barriers, such as the blood–brain barrier (BBB) and the endothelium of the arteries and veins. A reversible opening strategy to increase the permeability of drugs across the BBB could lead to improved therapies due to enhanced drug bioavailability. Vanilloids, such as capsaicin, are known to reversibly open tight junctions of epithelial and endothelial cells. In this study, we used several in vitro assays with the murine endothelial capillary brain cells (line cEND) as a BBB model to characterize the interaction between capsaicin and endothelial tight junctions. Full article
(This article belongs to the Special Issue Blood-Brain Barrier in CNS Injury and Repair, Volume 2)
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Review

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16 pages, 938 KiB  
Review
Blood–Brain Barrier, Lymphatic Clearance, and Recovery: Ariadne’s Thread in Labyrinths of Hypotheses
by Oxana Semyachkina-Glushkovskaya, Dmitry Postnov and Jürgen Kurths
Int. J. Mol. Sci. 2018, 19(12), 3818; https://doi.org/10.3390/ijms19123818 - 30 Nov 2018
Cited by 30 | Viewed by 7301
Abstract
The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic diseases. The lymphatic clearance of different tissues from waste products, viruses, bacteria, and toxic proteins significantly contributes to the correspondent [...] Read more.
The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic diseases. The lymphatic clearance of different tissues from waste products, viruses, bacteria, and toxic proteins significantly contributes to the correspondent recovery processes. However, understanding of the cerebral lymphatic functions is a challenging problem. The exploration of mechanisms of lymphatic communication with brain fluids as well as the role of the lymphatic system in brain drainage, clearance, and recovery is still in its infancy. Here we review novel concepts on the anatomy and physiology of the lymphatics in the brain, which warrant a substantial revision of our knowledge about the role of lymphatics in the rehabilitation of the brain functions after neural pathologies. We discuss a new vision on the connective bridge between the opening of a blood–brain barrier and activation of the meningeal lymphatic clearance. The ability to stimulate the lymph flow in the brain, is likely to play an important role in developing future innovative strategies in neurorehabilitation therapy. Full article
(This article belongs to the Special Issue Blood-Brain Barrier in CNS Injury and Repair, Volume 2)
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22 pages, 1192 KiB  
Review
Blood‒Brain Barrier Pathology and CNS Outcomes in Streptococcus pneumoniae Meningitis
by Belinda Yau, Nicholas H. Hunt, Andrew J. Mitchell and Lay Khoon Too
Int. J. Mol. Sci. 2018, 19(11), 3555; https://doi.org/10.3390/ijms19113555 - 11 Nov 2018
Cited by 36 | Viewed by 9956
Abstract
Streptococcus pneumoniae is a major meningitis-causing pathogen globally, bringing about significant morbidity and mortality, as well as long-term neurological sequelae in almost half of the survivors. Subsequent to nasopharyngeal colonisation and systemic invasion, translocation across the blood‒brain barrier (BBB) by S. pneumoniae is [...] Read more.
Streptococcus pneumoniae is a major meningitis-causing pathogen globally, bringing about significant morbidity and mortality, as well as long-term neurological sequelae in almost half of the survivors. Subsequent to nasopharyngeal colonisation and systemic invasion, translocation across the blood‒brain barrier (BBB) by S. pneumoniae is a crucial early step in the pathogenesis of meningitis. The BBB, which normally protects the central nervous system (CNS) from deleterious molecules within the circulation, becomes dysfunctional in S. pneumoniae invasion due to the effects of pneumococcal toxins and a heightened host inflammatory environment of cytokines, chemokines and reactive oxygen species intracranially. The bacteria‒host interplay within the CNS likely determines not only the degree of BBB pathological changes, but also host survival and the extent of neurological damage. This review explores the relationship between S. pneumoniae bacteria and the host inflammatory response, with an emphasis on the BBB and its roles in CNS protection, as well as both the acute and long-term pathogenesis of meningitis. Full article
(This article belongs to the Special Issue Blood-Brain Barrier in CNS Injury and Repair, Volume 2)
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