Transient use of a systemic adenosine kinase inhibitor attenuates epilepsy development in mice

Epilepsia
Ursula S SandauDetlev Boison

Abstract

Over one-third of all patients with epilepsy are refractory to treatment and there is an urgent need to develop new drugs that can prevent the development and progression of epilepsy. Epileptogenesis is characterized by distinct histopathologic and biochemical changes, which include astrogliosis and increased expression of the adenosine-metabolizing enzyme adenosine kinase (ADK; EC 2.7.1.20). Increased expression of ADK contributes to epileptogenesis and is therefore a target for therapeutic intervention. We tested the prediction that the transient use of an ADK inhibitor administered during the latent phase of epileptogenesis can mitigate the development of epilepsy. We used the intrahippocampal kainic acid (KA) mouse model of temporal lobe epilepsy, which is characterized by ipsilateral hippocampal sclerosis with granule cell dispersion and the development of recurrent hippocampal paroxysmal discharges (HPDs). KA-injected mice were treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 1.6 mg/kg, b.i.d., i.p.) during the latent phase of epileptogenesis from day 3-8 after injury; the period when gradual increases in hippocampal ADK expression begin to manifest. HPDs were assessed at 6 and 9 weeks after KA administration follo...Continue Reading

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Citations

Jan 16, 2020·Epilepsy Currents·Devin K BinderUNKNOWN AES/NINDS Epilepsy Benchmarks Stewards
Jun 23, 2020·Journal of Caffeine and Adenosine Research·Fabio C TescarolloDetlev Boison
Sep 22, 2020·Journal of Caffeine and Adenosine Research·David N RuskinSusan A Masino
Jan 29, 2020·Current Neuropharmacology·Nian YuQing Di
Dec 12, 2020·The European Journal of Neuroscience·Iman Imtiyaz Ahmed Juvale, Ahmad Tarmizi Che Has
Sep 10, 2019·Neuropharmacology·Pavel Klein, Ivana Tyrlikova
Aug 28, 2019·Progress in Neurobiology·Ying YuJianxiong Jiang
Dec 10, 2020·Therapeutic Advances in Chronic Disease·Chongyang TangTianfu Li
Nov 9, 2020·Biochemical Pharmacology·Detlev Boison, Michael F Jarvis
May 8, 2021·Neurochemistry International·Madhuvika MuruganDetlev Boison
Jun 1, 2021·Frontiers in Pharmacology·Mercedes Garcia-GilMaria Grazia Tozzi
Jun 19, 2021·Progress in Neurobiology·Edward BeamerTobias Engel
Nov 20, 2021·Neurochemical Research·Haiju ZhangBaozhen Yao

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