scholarly journals Pathomechanisms of Blood-Brain Barrier Disruption in ALS

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Nicholas Kakaroubas ◽  
Samuel Brennan ◽  
Matthew Keon ◽  
Nitin K. Saksena
Keyword(s):  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Neurological Processes ◽  
Brain Barrier Disruption ◽  
Pass Through ◽  
Blood Spinal Cord Barrier ◽  
Novel Therapeutic Strategies

The blood-brain barrier (BBB) and the blood-spinal cord barrier (BSCB) are responsible for controlling the microenvironment within neural tissues in humans. These barriers are fundamental to all neurological processes as they provide the extreme nutritional demands of neural tissue, remove wastes, and maintain immune privileged status. Being a semipermeable membrane, both the BBB and BSCB allow the diffusion of certain molecules, whilst restricting others. In amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases, these barriers become hyperpermeable, allowing a wider variety of molecules to pass through leading to more severe and more rapidly progressing disease. The intention of this review is to discuss evidence that BBB hyperpermeability is potentially a disease driving feature in ALS and other neurodegenerative diseases. The various biochemical, physiological, and genomic factors that can influence BBB permeability in ALS and other neurodegenerative diseases are also discussed, in addition to novel therapeutic strategies centred upon the BBB.

scholarly journals Epigenetics in blood–brain barrier disruption

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Stephanie A. Ihezie ◽  
Iny Elizebeth Mathew ◽  
Devin W. McBride ◽  
Ari Dienel ◽  
Spiros L. Blackburn ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Barrier Properties ◽  
Brain Barrier ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Gene Level ◽  
The Central Nervous System ◽  
Brain Barrier Disruption ◽  
Novel Therapeutic Strategies ◽  
Brain Homeostasis

AbstractThe vessels of the central nervous system (CNS) have unique barrier properties. The endothelial cells (ECs) which comprise the CNS vessels contribute to the barrier via strong tight junctions, specific transporters, and limited endocytosis which combine to protect the brain from toxins and maintains brain homeostasis. Blood–brain barrier (BBB) leakage is a serious secondary injury in various CNS disorders like stroke, brain tumors, and neurodegenerative disorders. Currently, there are no drugs or therapeutics available to treat specifically BBB damage after a brain injury. Growing knowledge in the field of epigenetics can enhance the understanding of gene level of the BBB and has great potential for the development of novel therapeutic strategies or targets to repair a disrupted BBB. In this brief review, we summarize the epigenetic mechanisms or regulators that have a protective or disruptive role for components of BBB, along with the promising approaches to regain the integrity of BBB.

The treatment of brain metastasis from breast cancer, role of blood-brain barrier disruption and early experience with trastuzumab

Therapy ◽  
2006 ◽  
Vol 3 (1) ◽  
pp. 97-112 ◽  
Author(s):  
Rose Marie Tyson ◽  
Dale F Kraemer ◽  
Matthew A Hunt ◽  
Leslie L Muldoon ◽  
Peter Orbay ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Blood Brain Barrier ◽  
Early Experience ◽  
Brain Barrier ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption

scholarly journals Combined Perfusion and Permeability Imaging Reveals Different Pathophysiologic Tissue Responses After Successful Thrombectomy

2021 ◽  
Author(s):  
Arne Potreck ◽  
Matthias A. Mutke ◽  
Charlotte S. Weyland ◽  
Johannes A. R. Pfaff ◽  
Peter A. Ringleb ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Blood Brain Barrier ◽  
Hemorrhagic Transformation ◽  
Brain Barrier ◽  
Dynamic Susceptibility ◽  
Blood Brain Barrier Disruption ◽  
Flow Maps ◽  
Blood Brain ◽  
Patients At Risk ◽  
Brain Barrier Disruption

AbstractDespite successful recanalization of large-vessel occlusions in acute ischemic stroke, individual patients profit to a varying degree. Dynamic susceptibility-weighted perfusion and dynamic T1-weighted contrast-enhanced blood-brain barrier permeability imaging may help to determine secondary stroke injury and predict clinical outcome. We prospectively performed perfusion and permeability imaging in 38 patients within 24 h after successful mechanical thrombectomy of an occlusion of the middle cerebral artery M1 segment. Perfusion alterations were evaluated on cerebral blood flow maps, blood-brain barrier disruption (BBBD) visually and quantitatively on ktrans maps and hemorrhagic transformation on susceptibility-weighted images. Visual BBBD within the DWI lesion corresponded to a median ktrans elevation (IQR) of 0.77 (0.41–1.4) min−1 and was found in all 7 cases of hypoperfusion (100%), in 10 of 16 cases of hyperperfusion (63%), and in only three of 13 cases with unaffected perfusion (23%). BBBD was significantly associated with hemorrhagic transformation (p < 0.001). While BBBD alone was not a predictor of clinical outcome at 3 months (positive predictive value (PPV) = 0.8 [0.56–0.94]), hypoperfusion occurred more often in patients with unfavorable clinical outcome (PPV = 0.43 [0.10–0.82]) compared to hyperperfusion (PPV = 0.93 [0.68–1.0]) or unaffected perfusion (PPV = 1.0 [0.75–1.0]). We show that combined perfusion and permeability imaging reveals distinct infarct signatures after recanalization, indicating the severity of prior ischemic damage. It assists in predicting clinical outcome and may identify patients at risk of stroke progression.

scholarly journals Blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bailey Hiles-Murison ◽  
Andrew P. Lavender ◽  
Mark J. Hackett ◽  
Joshua J. Armstrong ◽  
Michael Nesbit ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Brain Barrier ◽  
Hippocampal Formation ◽  
Brain Barrier ◽  
Lateral Ventricles ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption ◽  
Underlying Mechanisms

AbstractRepeated sub-concussive impact (e.g. soccer ball heading), a significantly lighter form of mild traumatic brain injury, is increasingly suggested to cumulatively alter brain structure and compromise neurobehavioural function in the long-term. However, the underlying mechanisms whereby repeated long-term sub-concussion induces cerebral structural and neurobehavioural changes are currently unknown. Here, we utilised an established rat model to investigate the effects of repeated sub-concussion on size of lateral ventricles, cerebrovascular blood–brain barrier (BBB) integrity, neuroinflammation, oxidative stress, and biochemical distribution. Following repeated sub-concussion 3 days per week for 2 weeks, the rats showed significantly enlarged lateral ventricles compared with the rats receiving sham-only procedure. The sub-concussive rats also presented significant BBB dysfunction in the cerebral cortex and hippocampal formation, whilst neuromotor function assessed by beamwalk and rotarod tests were comparable to the sham rats. Immunofluorescent and spectroscopic microscopy analyses revealed no significant changes in neuroinflammation, oxidative stress, lipid distribution or protein aggregation, within the hippocampus and cortex. These data collectively indicate that repeated sub-concussion for 2 weeks induce significant ventriculomegaly and BBB disruption, preceding neuromotor deficits.

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