Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravation.

Adenosine kinase (ADK) is considered to be the key regulator of the brain's endogenous anticonvulsant, adenosine. In adult brain, ADK is primarily expressed in a subpopulation of astrocytes and striking upregulation of ADK in these cells has been associated with astrogliosis after kainic acid-induced status epilepticus (KASE) in the kainic acid mouse model of temporal lobe epilepsy. To investigate the causal relationship between KASE-induced astrogliosis, upregulation of ADK and seizure activity, we have developed a novel mouse model [the Adktm1(-/-)-Tg(UbiAdk) mouse] lacking the endogenous astrocytic enzyme due to a targeted disruption of the endogenous gene, but containing an Adk transgene under the control of a human ubiquitin promoter.

Overexpression of adenosine kinase in epileptic hippocampus contributes to epileptogenesis.

Endogenous adenosine in the brain is thought to prevent the development and spread of seizures via a tonic anticonvulsant effect. Brain levels of adenosine are primarily regulated by the activity of adenosine kinase. To establish a link between adenosine kinase expression and seizure activity, we analyzed the expression of adenosine kinase in the brain of control mice and in a kainic acid-induced mouse model of mesial temporal lobe epilepsy.

entla, a novel epileptic and ataxic Cacna2d2 mutant of the mouse.

entla (ent) is a novel recessive phenotype of mice. The underlying mutation was mapped to chromosome 9 (60.1 centimorgans) and identified as an allele of the Cacna2d2 gene encoding the alpha2delta-2 subunit of voltage-gated calcium channels.

Seizure suppression by adenosine A1 receptor activation in a mouse model of pharmacoresistant epilepsy.

Purpose: Because of the high incidence of pharmacoresistance in the treatment of epilepsy (20-30%), alternative treatment strategies are needed. Recently a proof-of-principle for a new therapeutic approach was established by the intraventricular delivery of adenosine released from implants of engineered cells. Adenosine-releasing implants were found to be effective in seizure suppression in a rat model of temporal lobe epilepsy.