A Novel Murine Neocortical Epilepsy Model Created by Over-expression of Adenosine Kinase (ADK) in Cortical AstrocytesKeywords: epilepsy, cortex, animal model, seizures, astrocyteInteractive Manuscript
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What is the background behind your study?
Animal models of epileptogenesis have been developed that closely mimic the pathogenesis of human mesial temporal lobe epilepsy, while physiological animal models for neocortical epilepsy are lacking. Recent evidence indicates that abnormal expression of adenosine kinase (ADK) is implicated in epileptogenesis.
What is the purpose of your study?
We have developed a novel neocortical epilepsy model by inducing over-expression of ADK in cortical astrocytes in mice.
Describe your patient group.
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Describe what you did.
Healthy adult male mice received a stereotactic intracortical injection of viral vectors that overexpress ADK cDNA or null viral particles without ADK cDNA (control) in a focal area of the left hemisphere. Implanted electrodes were employed to record seizure phenotype. ADK expression levels in the viral injection region were determined using immunohistochemistry. The effect of ADK over-expression on cerebral blood flow (CBF) was measured using a three-dimensional high resolution imaging technique based on the optical property of biological tissues.
Describe your main findings.
Utilizing immunohistochemistry, we confirmed that the viral delivery of ADK cDNA created a distinct focal region of over-expressed ADK in cortical astrocytes. Implanted electrodes recorded focal spontaneous nonconvulsive electrographic seizures originating from all sites of ADK overexpression. In the control animals, no ADK overexpression or focal seizure activity was observed. Furthermore, in regions of ADK overexpression, there was a reduction in CBF of approximately 23% and 29% compared to control and the contralateral hemisphere in the same animal, respectively.
Describe the main limitation of this study.
This is a mouse study.
Describe your main conclusion.
We have developed a novel neocortical epilepsy model based on the abnormal adenosine metabolism implicated in focal epileptogenesis. We have quantitatively demonstrated that focal seizure activity resulting from ADK overexpression is associated with a reduction of CBF in the same region.
Describe the importance of your findings and how they can be used by others.
This suggests that regulation of CBF by adenosine and ADK may play an important role in neocortical epilepogenesis. This murine model may be suitable for investigating both medical and surgical treatments of neocortical epilepsy.
Animal models of epileptogenesis have been developed that closely mimic the pathogenesis of human mesial temporal lobe epilepsy, while physiological animal models for neocortical epilepsy are lacking. Recent evidence indicates that abnormal expression of adenosine kinase (ADK) is implicated in epileptogenesis.
We have developed a novel neocortical epilepsy model by inducing over-expression of ADK in cortical astrocytes in mice.
Healthy adult male mice received a stereotactic intracortical injection of viral vectors that overexpress ADK cDNA or null viral particles without ADK cDNA (control) in a focal area of the left hemisphere. Implanted electrodes were employed to record seizure phenotype. ADK expression levels in the viral injection region were determined using immunohistochemistry. The effect of ADK over-expression on cerebral blood flow (CBF) was measured using a three-dimensional high resolution imaging technique based on the optical property of biological tissues.
Utilizing immunohistochemistry, we confirmed that the viral delivery of ADK cDNA created a distinct focal region of over-expressed ADK in cortical astrocytes. Implanted electrodes recorded focal spontaneous nonconvulsive electrographic seizures originating from all sites of ADK overexpression. In the control animals, no ADK overexpression or focal seizure activity was observed. Furthermore, in regions of ADK overexpression, there was a reduction in CBF of approximately 23% and 29% compared to control and the contralateral hemisphere in the same animal, respectively.
This is a mouse study.
We have developed a novel neocortical epilepsy model based on the abnormal adenosine metabolism implicated in focal epileptogenesis. We have quantitatively demonstrated that focal seizure activity resulting from ADK overexpression is associated with a reduction of CBF in the same region.
This suggests that regulation of CBF by adenosine and ADK may play an important role in neocortical epilepogenesis. This murine model may be suitable for investigating both medical and surgical treatments of neocortical epilepsy.
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