Personalized translational epilepsy research — Novel approaches and future perspectives

Bauer, Sebastian; Alphen, Natascha van; Becker, Albert; Chiocchetti, Andreas G.; Deichmann, Ralf; Deller, Thomas; Freiman, Thomas M.; Freitag, Christine M.; Gehrig, Johannes; Hermsen, A.; Jedlicka, Paul; Kell, Christian A.; Klein, Karl Martin; Knake, Susanne; Kullmann, Dimitri M.; Liebner, Stefan; Norwood, Braxton A.; Omigie, Diana; Plate, Karl-Heinz; Reif, Andreas; Reif, Philipp S.; Reiss, Yvonne; Roeper, Jochen; Ronellenfitsch, Michael; Schorge, Stephanie; Schratt, Gerhard; Schwarzacher, Stephan W.; Steinbach, Joachim P.; Strzelczyk, Adam; Triesch, Jochen; Wagner, Marlies; Walker, Matthew C.; Wegner, Frederic von; Rosenow, Felix

doi:10.1016/j.yebeh.2017.06.040

Cited by 15 publications

(7 citation statements)

References 27 publications

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“…The restoration of Tie2 signalling may also have implications for other disorders associated with defective BBB, i.e. stroke [43], epilepsy [11] and metastasis whereby disease onset may be prevented by vascular stabilising agents.…”

Section: Role Of the Bbb In Glioma-associated Inflammation/immune Celmentioning

confidence: 99%

Functional morphology of the blood–brain barrier in health and disease

et al. 2018

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The adult quiescent blood-brain barrier (BBB), a structure organised by endothelial cells through interactions with pericytes, astrocytes, neurons and microglia in the neurovascular unit, is highly regulated but fragile at the same time. In the past decade, there has been considerable progress in understanding not only the molecular pathways involved in BBB development, but also BBB breakdown in neurological diseases. Specifically, the Wnt/β-catenin, retinoic acid and sonic hedgehog pathways moved into the focus of BBB research. Moreover, angiopoietin/Tie2 signalling that is linked to angiogenic processes has gained attention in the BBB field. Blood vessels play an essential role in initiation and progression of many diseases, including inflammation outside the central nervous system (CNS). Therefore, the potential influence of CNS blood vessels in neurological diseases associated with BBB alterations or neuroinflammation has become a major focus of current research to understand their contribution to pathogenesis. Moreover, the BBB remains a major obstacle to pharmaceutical intervention in the CNS. The complications may either be expressed by inadequate therapeutic delivery like in brain tumours, or by poor delivery of the drug across the BBB and ineffective bioavailability. In this review, we initially describe the cellular and molecular components that contribute to the steady state of the healthy BBB. We then discuss BBB alterations in ischaemic stroke, primary and metastatic brain tumour, chronic inflammation and Alzheimer's disease. Throughout the review, we highlight common mechanisms of BBB abnormalities among these diseases, in particular the contribution of neuroinflammation to BBB dysfunction and disease progression, and emphasise unique aspects of BBB alteration in certain diseases such as brain tumours. Moreover, this review highlights novel strategies to monitor BBB function by non-invasive imaging techniques focussing on ischaemic stroke, as well as novel ways to modulate BBB permeability and function to promote treatment of brain tumours, inflammation and Alzheimer's disease. In conclusion, a deep understanding of signals that maintain the healthy BBB and promote fluctuations in BBB permeability in disease states will be key to elucidate disease mechanisms and to identify potential targets for diagnostics and therapeutic modulation of the BBB.

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Section: Role Of the Bbb In Glioma-associated Inflammation/immune Celmentioning

confidence: 99%

Functional morphology of the blood–brain barrier in health and disease

et al. 2018

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“…The findings described above may contribute to the development of personalized approaches to the treatment of epilepsy, whose motto is to treat a particular patient and not a disease in general [97]. Due to the poly-etiological nature of epilepsy, most epileptologists agree that such approaches will pave the way to highefficacy antiepileptic therapy [98,99].…”

Section: Resultsmentioning

confidence: 99%

Individual Approaches to Diagnosis and Treatment of Epilepsia (Review)

Zemlyanaya¹,

Федотчев²

2018

Sovrem Tehnol Med

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Epilepsy is one of the most common and treatment-resistant neurological diseases; it has heterogenic manifestations and requires individual approaches to its diagnosis and treatment. The ground for such approaches has been laid by modern science-based technologies, currently available in clinical practice. The aim of this review is to analyze publications on personalized approaches to the diagnosis and treatment of epilepsy over the past 10 years. In this review, we discuss the issue of individual markers of epilepsy and their predictive power, new approaches to localizing the epileptic foci, the relationship between the left-sided, right-sided and interhemispheric asymmetry and epileptogenesis, the role of comorbid disorders in epilepsy, as well as the available options for identifying the predictors of treatment efficacy.

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“…Maßgeschneiderte Therapieansätze sind über die letzten Jahre zunehmend in den Fokus der medizinischen Forschung gerückt und gelten insbesondere im Bereich der Epileptologie als vielversprechende zukünftige Behandlungsoptionen [33][34][35]. Mit EVE steht bei Patienten mit TSC eines der wenigen, bereits aktuell verfügbaren krankheitsspezifischen und krankheitsmodulierenden ("disease modifying therapy" [DMT]) Medikamente in der Behandlung von Epilepsie zur Verfügung, wobei EVE pathophysiologisch unmittelbar in den durch die bisher bekannten Mutationen des TSC1-oder TSC2-Gens eingreift und die fehlende regulierende Funktion des TSC-Proteinkomplexes auf den mTOR-Signalweg zumindest teilweise zu restituieren vermag [4,35].…”

Section: Diskussionunclassified

Everolimus als krankheitsspezifische Therapieoption bei mit tuberöser Sklerose assoziierter, therapierefraktärer Epilepsie – ein systematischer Überblick

2021

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ZusammenfassungTuberöse Sklerose („tuberous sclerosis complex“ [TSC]) ist eine seltene genetische Erkrankung, die neben kutanen und viszeralen Organmanifestationen typischerweise bereits in einem sehr frühen Erkrankungsstadium mit einer schweren, meist therapierefraktären Epilepsie einhergeht. Aufgrund seiner direkten Wirkung am durch TSC dysregulierten mTOR-Signalweg sowie der synergistischen Effekte auf andere Organmanifestationen kommt das Rapamycin-Derivat Everolimus (EVE) zunehmend zur Anwendung. Ziel dieses systematischen Reviews ist, die Wirksamkeit, Sicherheit und Verträglichkeit von EVE bei Patienten mit TSC-assoziierter, therapierefraktärer Epilepsie aufzuarbeiten.

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Personalized translational epilepsy research — Novel approaches and future perspectives

Cited by 15 publications

References 27 publications

Functional morphology of the blood–brain barrier in health and disease

Functional morphology of the blood–brain barrier in health and disease

Individual Approaches to Diagnosis and Treatment of Epilepsia (Review)

Everolimus als krankheitsspezifische Therapieoption bei mit tuberöser Sklerose assoziierter, therapierefraktärer Epilepsie – ein systematischer Überblick

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