Role of adenosine in status epilepticus: A potential new target?
Open Access
- 3 September 2013
- Vol. 54 (s6), 20-22
- https://doi.org/10.1111/epi.12268
Abstract
The homeostatic bioenergetic network regulator adenosine is an endogenous anticonvulsant of the brain that plays critical roles in seizure termination and postictal refractoriness. Adenosine homeostasis in the adult brain is largely under the control of metabolic clearance through adenosine kinase (ADK), expressed predominantly in astrocytes. The role of adenosine in status epilepticus (SE) appears to be a double‐edged sword. We demonstrated that the severity of an SE clearly depends on the expression levels of ADK. A genetic knockdown of ADK prevented SE in a mouse model, whereas transgenic overexpression of the enzyme aggravated the SE. Therefore, ADK inhibition or adenosine augmentation might be a therapeutic strategy to terminate or attenuate an SE. On the other hand, SE triggers a surge of endogenous adenosine, which may initiate secondary events leading to epileptogenesis. Two new findings point into this direction: (1) Elevated adenosine triggers changes in the epigenome; and (2) SE triggers transient changes in ADK expression, which have been linked to neurogenesis. Although the ADK/adenosine system is an attractive target for the attenuation of an SE, the same system may also trigger downstream events related to epileptogenesis.Keywords
This publication has 25 references indexed in Scilit:
- Epigenetic changes induced by adenosine augmentation therapy prevent epileptogenesisJCI Insight, 2013
- Adenosine kinase inhibition selectively promotes rodent and porcine islet β-cell replicationProceedings of the National Academy of Sciences, 2012
- A ketogenic diet suppresses seizures in mice through adenosine A1 receptorsJCI Insight, 2011
- Adenosine kinase regulation of cardiomyocyte hypertrophyAmerican Journal of Physiology-Heart and Circulatory Physiology, 2011
- Adenosine kinase determines the degree of brain injury after ischemic stroke in miceJournal of Cerebral Blood Flow & Metabolism, 2011
- International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An UpdatePharmacological Reviews, 2011
- Inhibitory RNA in epilepsy: Research tools and therapeutic perspectivesEpilepsia, 2010
- Adenosine augmentation therapies (AATs) for epilepsy: Prospect of cell and gene therapiesEpilepsy Research, 2009
- Adenosine kinase is a target for the prediction and prevention of epileptogenesis in miceJCI Insight, 2008
- Lentiviral RNAi-induced downregulation of adenosine kinase in human mesenchymal stem cell grafts: A novel perspective for seizure controlExperimental Neurology, 2007