Mechanisms of epileptogenesis and potential treatment targets

• Published in: Lancet neurology Vol. 10; no. 2; pp. 173 - 186
• Main Authors: Pitkänen, Asla, Lukasiuk, Katarzyna
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2011; Elsevier Limited
• Subjects: Animal models; Animals; Antibodies; Anticonvulsants - administration & dosage; Antiepileptic agents; Brain injury; Cell death; Convulsions & seizures; Disease prevention; Drug Delivery Systems - trends; Endothelial cells; Epilepsy; Epilepsy - drug therapy; Epilepsy - etiology; Epilepsy - genetics; Gene expression; Genetic Therapy - trends; GNP; Gross National Product; Humans; Immune response; Immunosuppressive agents; Inflammation; Leukocytes; Medical research; Neural networks; Neurobiology; Neurology; Neurotrophic factors; Plasticity (neural); Traumatic brain injury; Treatment Outcome
• ISSN: 1474-4422; 1474-4465; 1474-4465
• DOI: 10.1016/S1474-4422(10)70310-0

Prevention of epileptogenesis after brain trauma is an unmet medical challenge. Recent molecular profiling studies have provided an insight into molecular changes that contribute to formation of ictogenic neuronal networks, including genes regulating synaptic or neuronal plasticity, cell death, proliferation, and inflammatory or immune responses. These mechanisms have been targeted to prevent epileptogenesis in animal models. Favourable effects have been obtained using immunosuppressants, antibodies blocking adhesion of leucocytes to endothelial cells, gene therapy driving expression of neurotrophic factors, pharmacological neurostimulation, or even with conventional antiepileptic drugs by administering them before the appearance of genetic epilepsy. Further studies are needed to clarify the optimum time window and aetiological specificity of treatments. Questions related to adverse events also need further consideration. Encouragingly, the recent experimental studies emphasise that the complicated process of epileptogenesis can be favourably modified, and that antiepileptogenesis as a treatment indication might not be an impossible mission.