Blood–Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models DOI Open Access
Sarah E. Brandl, Markus Reindl

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12699 - 12699

Published: Aug. 11, 2023

The blood-brain barrier, which is formed by tightly interconnected microvascular endothelial cells, separates the brain from peripheral circulation. Together with other central nervous system-resident cell types, including pericytes and astrocytes, barrier forms neurovascular unit. Upon neuroinflammation, this becomes leaky, allowing molecules cells to enter potentially harm tissue of system. Despite significance animal models in research, they may not always adequately reflect human pathophysiology. Therefore, are needed. This review will provide an overview terms both health disease. It describe all key elements vitro explore how different compositions can be utilized effectively model a variety neuroinflammatory conditions. Furthermore, it existing types that used basic research study respective pathologies thus far.

Language: Английский

Insights into epileptogenesis from post-traumatic epilepsy DOI
Matthew Pease, Kunal Gupta, Solomon L. Moshé

et al.

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(5), P. 298 - 312

Published: April 3, 2024

Language: Английский

Citations

19
Crossing the blood–brain barrier: emerging therapeutic strategies for neurological disease DOI

Josephine H Pedder,

Adam M. Sonabend,

Michael D Cearns

et al.

The Lancet Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

3
Reactive Glia Inflammatory Signaling Pathways and Epilepsy DOI Open Access
Pascual Sanz, María Adelaida García-Gimeno

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(11), P. 4096 - 4096

Published: June 8, 2020

Neuroinflammation and epilepsy are interconnected. Brain inflammation promotes neuronal hyper-excitability seizures, dysregulation in the glia immune-inflammatory function is a common factor that predisposes or contributes to generation of seizures. At same time, acute seizures upregulate production pro-inflammatory cytokines microglia astrocytes, triggering downstream cascade inflammatory mediators. Therefore, epileptic mediators form vicious positive feedback loop, reinforcing each other. In this work, we have reviewed main glial signaling pathways involved neuroinflammation, how they affected conditions, therapeutic opportunities offer prevent these disorders.

Language: Английский

Citations

133
Astrocytes in the regulation of cerebrovascular functions DOI
Martine Cohen‐Salmon,

Leila Slaoui,

Noémie Mazaré

et al.

Glia, Journal Year: 2020, Volume and Issue: 69(4), P. 817 - 841

Published: Oct. 15, 2020

Astrocytes are the most numerous type of neuroglia in brain and have a predominant influence on cerebrovascular system; they control perivascular homeostasis, integrity blood-brain barrier, dialogue with peripheral immune system, transfer metabolites from blood, blood vessel contractility response to neuronal activity. These regulatory processes occur specialized interface composed astrocyte extensions that almost completely cover cerebral vessels. Scientists only recently started study how this is formed it influences functions. Here, we review literature astrocytes' role regulation system. We anatomy development gliovascular interface, known functions, molecular factors, latter's implication certain pathophysiological situations, recent cutting-edge experimental tools developed examine at vascular interface. Finally, highlight some open questions field research.

Language: Английский

Citations

71
Sex differences in the blood–brain barrier: Implications for mental health DOI Creative Commons
Laurence Dion‐Albert, Luisa Bandeira Binder, Béatrice Daigle

et al.

Frontiers in Neuroendocrinology, Journal Year: 2022, Volume and Issue: 65, P. 100989 - 100989

Published: March 8, 2022

Prevalence of mental disorders, including major depressive disorder (MDD), bipolar (BD) and schizophrenia (SZ) are increasing at alarming rates in our societies. Growing evidence points toward sex differences these conditions, high treatment resistance support the need to consider novel biological mechanisms outside neuronal function gain mechanistic insights that could lead innovative therapies. Blood-brain barrier alterations have been reported MDD, BD SZ. Here, we provide an overview sex-specific immune, endocrine, vascular transcriptional-mediated changes affect neurovascular integrity possibly contribute pathogenesis disorders. We also identify pitfalls current literature highlight promising biomarkers. Better understanding how adaptations can health status is essential not only context SZ but cardiovascular diseases stroke which associated with higher prevalence conditions.

Language: Английский

Citations

63
TGF-β as a Key Modulator of Astrocyte Reactivity: Disease Relevance and Therapeutic Implications DOI Creative Commons
Jian Luo

Biomedicines, Journal Year: 2022, Volume and Issue: 10(5), P. 1206 - 1206

Published: May 23, 2022

Astrocytes are essential for normal brain development and functioning. They respond to injury disease through a process referred as reactive astrogliosis, where the reactivity is highly heterogenous context-dependent. Reactive astrocytes active contributors pathology can exert beneficial, detrimental, or mixed effects following insults. Transforming growth factor-β (TGF-β) has been identified one of key factors regulating astrocyte reactivity. The genetic pharmacological manipulation TGF-β signaling pathway in animal models central nervous system (CNS) alters pathological functional outcomes. This review aims provide recent understanding regarding injury, aging, neurodegeneration. Further, it explores how modulates function context CNS injury.

Language: Английский

Citations

61
CNS pharmacology of NKCC1 inhibitors DOI Creative Commons
Wolfgang Löscher, Kai Kaila

Neuropharmacology, Journal Year: 2021, Volume and Issue: 205, P. 108910 - 108910

Published: Dec. 6, 2021

The Na-K-2Cl cotransporter NKCC1 and the neuron-specific K-Cl KCC2 are considered attractive CNS drug targets because altered neuronal chloride regulation consequent effects on GABAergic signaling have been implicated in numerous disorders. While modulators not yet clinically available, loop diuretic bumetanide has used clinical studies to treat brain disorders as a tool for inhibition preclinical models. Bumetanide is known anticonvulsant neuroprotective under some pathophysiological conditions. However, shown several species from neonates adults (mice, rats, dogs, by extrapolation humans), at low doses of approved diuresis, this negligible access into CNS, reaching levels that much lower than what needed inhibit cells within parenchyma. Several discovery strategies over last ∼15 years develop brain-permeant compounds that, ideally, should be selective eliminate diuresis mediated renal NKCC2. employed improve pharmacokinetic pharmacodynamic properties blockers include evaluation other diuretics; development lipophilic prodrugs bumetanide; side-chain derivatives unbiased high-throughput screening approaches based large chemical compound libraries. main outcomes (1), non-acidic diuretics such azosemide torasemide may advantages inhibitors vs. (2), achieve significantly higher parent activity; (3), novel do exhibit any functionally relevant improvement accessibility or selectivity (4) discovered resolve inherent problems bumetanide, but achieved. Thus, further research optimize design inhibitors. Another major challenge identify mechanisms whereby various NKCC1-expressing cellular these (e.g., neurons, oligodendrocytes astrocytes) outside parenchyma blood-brain barrier, choroid plexus, endocrine immune system), well molecular off-target effects, might contribute their reported therapeutic adverse effects.

Language: Английский

Citations

59
Dogs as a Natural Animal Model of Epilepsy DOI Creative Commons
Wolfgang Löscher

Frontiers in Veterinary Science, Journal Year: 2022, Volume and Issue: 9

Published: June 22, 2022

Epilepsy is a common neurological disease in both humans and domestic dogs, making dogs an ideal translational model of epilepsy. In species, epilepsy complex brain characterized by enduring predisposition to generate spontaneous recurrent epileptic seizures. Furthermore, as humans, status epilepticus one the more emergencies with not single but group disorders broad array clinical signs, age onset, underlying causes. Brain imaging suggests that limbic system, including hippocampus cingulate gyrus, often affected canine epilepsy, which could explain high incidence comorbid behavioral problems such anxiety cognitive alterations. Resistance antiseizure medications significant problem human so can be used study mechanisms drug resistance develop novel therapeutic strategies benefit species. Importantly, are large enough accommodate intracranial EEG responsive neurostimulation devices designed for humans. Studies have reported ictal interictal events remarkably similar those occurring Continuous (24/7) recordings select >1 year provided rich dataset unprecedented length studying seizure periodicities developing new methods forecasting. The data presented this review substantiate excellent several facets research. techniques inducing seizures laboratory discussed related advances. development vagus nerve stimulation therapy drug-resistant people was based on series studies induced Dogs naturally or provide large-animal models bridge gap between rodents therapies. because dog only preclinical species medicine also potential patient pet, research serves veterinary medicine.

Language: Английский

Citations

40
Circadian rhythms in the blood–brain barrier: impact on neurological disorders and stress responses DOI Creative Commons
Nicolette Schurhoff, Michał Toborek

Molecular Brain, Journal Year: 2023, Volume and Issue: 16(1)

Published: Jan. 12, 2023

Circadian disruption has become more prevalent in society due to the increase shift work, sleep disruption, blue light exposure, and travel via different time zones. The circadian rhythm is a timed transcription-translation feedback loop with positive regulators, BMAL1 CLOCK, that interact negative CRY PER, regulate both central peripheral clocks. This review highlights functions of rhythm, specifically blood-brain barrier (BBB), during healthy pathological states. BBB highly selective dynamic interface composed CNS endothelial cells, astrocytes, pericytes, neurons, microglia form neurovascular unit (NVU). rhythms modulate integrity through regulating oscillations tight junction proteins, assisting NVU, modulating transporter functions. disruptions within have been observed stress responses several neurological disorders, including brain metastasis, epilepsy, Alzheimer's disease, Parkinson's disease. Further understanding these interactions may facilitate development improved treatment options preventative measures.

Language: Английский

Citations

40
In vivo methods for imaging blood–brain barrier function and dysfunction DOI Creative Commons
William J. Harris, Marie‐Claude Asselin, Rainer Hinz

et al.

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2022, Volume and Issue: 50(4), P. 1051 - 1083

Published: Nov. 28, 2022

Abstract The blood–brain barrier (BBB) is the interface between central nervous system and systemic circulation. It tightly regulates what enters removed from brain parenchyma fundamental in maintaining homeostasis. Increasingly, BBB recognised as having a significant role numerous neurological disorders, ranging acute disorders (traumatic injury, stroke, seizures) to chronic neurodegeneration (Alzheimer’s disease, vascular dementia, small vessel disease). Numerous approaches have been developed study vitro, vivo, ex vivo. complex multicellular structure effects of disease are difficult recreate accurately functional aspects cannot be easily studied As such, value vivo methods intact overstated. This review discusses function how these affected diseases. then depth several established novel for imaging with focus on MRI, nuclear imaging, high-resolution intravital fluorescence microscopy.

Language: Английский

Citations

39