Blood-Brain Barrier: From Physiology to Disease and Back

Physiological Reviews, Journal Year: 2018, Volume and Issue: 99(1), P. 21 - 78

Published: Oct. 3, 2018

The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At same time, BBB regulates transport of molecules into out central nervous system (CNS), which maintains tightly controlled chemical composition neuronal milieu that is required for proper functioning. In this review, we first examine molecular cellular mechanisms underlying establishment BBB. Then, focus on physiology, endothelial pericyte transporters, perivascular paravascular transport. Next, discuss rare human monogenic neurological disorders with primary genetic defect in BBB-associated cells demonstrating link between breakdown neurodegeneration. review effects genes inheritance and/or increased susceptibility Alzheimer's disease (AD), Parkinson's (PD), Huntington's disease, amyotrophic lateral sclerosis (ALS) relation to other pathologies deficits. We next how dysfunction relates deficits majority sporadic AD, PD, ALS cases, multiple sclerosis, neurodegenerative disorders, acute CNS such as stroke, traumatic brain injury, spinal cord epilepsy. Lastly, BBB-based therapeutic opportunities. conclude lessons learned future directions, emphasis technological advances investigate functions living brain, at level, address key unanswered questions.

Language: Английский

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Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders

Epilepsia, Journal Year: 2014, Volume and Issue: 55(6), P. 791 - 802

Published: May 22, 2014

To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regard to its relevance epilepsy and other selected neuropsychiatric disorders. We summarize presentations from conference in which invited participants reviewed relevant aspects physiology, mechanisms action, pharmacology, data studies animal models human subjects. Cannabis has been used treat disease since ancient times. Δ(9) -Tetrahydrocannabinol (Δ(9) -THC) is major psychoactive ingredient CBD nonpsychoactive cannabis. -THC are anticonvulsant most but can be proconvulsant some healthy animals. The psychotropic effects limit tolerability. many acute models, there limited chronic models. antiepileptic not known, may include on equilibrative nucleoside transporter; orphan G-protein-coupled receptor GPR55; transient potential vanilloid type-1 channel; 5-HT1a receptor; α3 α1 glycine receptors. neuroprotective antiinflammatory effects, it appears well tolerated humans, small methodologically have inconclusive. More recent anecdotal reports high-ratio CBD:Δ(9) medical marijuana claimed efficacy, were controlled. bears investigation disorders, including anxiety, schizophrenia, addiction, neonatal hypoxic-ischemic encephalopathy. However, we lack well-powered double-blind randomized, controlled efficacy pure for any disorder. Initial dose-tolerability focusing target intractable populations such as patients Dravet Lennox-Gastaut syndromes being planned. Trials treatment-resistant epilepsies also warranted. A PowerPoint slide summarizing this article available download Supporting Information section here.

Language: Английский

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Blood–brain barrier structure and function and the challenges for CNS drug delivery

Journal of Inherited Metabolic Disease, Journal Year: 2013, Volume and Issue: 36(3), P. 437 - 449

Published: April 22, 2013

Language: Английский

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Glia and epilepsy: excitability and inflammation

Trends in Neurosciences, Journal Year: 2013, Volume and Issue: 36(3), P. 174 - 184

Published: Jan. 5, 2013

Language: Английский

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Epilepsy

Nature Reviews Disease Primers, Journal Year: 2018, Volume and Issue: 4(1)

Published: May 3, 2018

Language: Английский

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Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy

Nature Reviews Neurology, Journal Year: 2019, Volume and Issue: 15(8), P. 459 - 472

Published: July 1, 2019

Language: Английский

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New avenues for anti-epileptic drug discovery and development

Nature Reviews Drug Discovery, Journal Year: 2013, Volume and Issue: 12(10), P. 757 - 776

Published: Sept. 20, 2013

Language: Английский

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Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation

Molecular Neurobiology, Journal Year: 2018, Volume and Issue: 56(5), P. 3295 - 3312

Published: Aug. 17, 2018

Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins in healthy and diseased brain. As a result, there large body evidence that associates BDNF with neuronal maintenance, survival, plasticity, neurotransmitter regulation. Patients psychiatric neurodegenerative disorders often have reduced concentrations their blood A current hypothesis suggests these abnormal levels might be due to chronic inflammatory state brain certain disorders, as neuroinflammation known affect several BDNF-related signaling pathways. Activation glia cells can induce an increase pro- antiinflammatory cytokines reactive oxygen species, which lead modulation function neurotoxicity observed pathologies. Understanding how involved brain, especially disease onset progression, crucial for development new strategies treatment. Despite increasing involvement scarce addresses interaction between neurotrophin diseases. This review focuses on effect acute inflammation common aims shed some light possible biological mechanisms may influence this effect. In addition, will address behavior pharmacological interventions disorders.

Language: Английский

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The role of inflammation in the development of epilepsy

Journal of Neuroinflammation, Journal Year: 2018, Volume and Issue: 15(1)

Published: May 15, 2018

Epilepsy, a neurological disease characterized by recurrent seizures, is often associated with history of previous lesions in the nervous system. Impaired regulation activation and resolution inflammatory cells molecules injured neuronal tissue critical factor to development epilepsy. However, it still unclear as how that unbalanced inflammation contributes Therefore, one goals epilepsy research identify elucidate interconnected pathways systemic disorders may further develop progression. In this paper, molecules, (rheumatoid arthritis, Crohn’s, Type I Diabetes, etc.) could contribute development, are reviewed. Understanding neurobiology epileptogenesis will new biomarkers for better screening patients at risk therapeutic targets both prophylaxis treatment

Language: Английский

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Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability

Neuropharmacology, Journal Year: 2014, Volume and Issue: 96, P. 70 - 82

Published: Nov. 8, 2014

Language: Английский

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