Epileptogenesis Epilepsy

NTs it is now appropriate to consider what evidence there is for a malfunction of NT activity in epilepsy, particularly in those responsible for primary excitation and inhibition, i.e. the amino acids. Before doing so the epileptogenesis of absence seizures (petit mal) justifies separate consideration. 

Anticonvulsant action of the nucleoside transport inhibitor, soluflazine, on synaptic and non-synaptic epileptogenesis in the guinea-pig hippocampus. Epilepsy Res. 2 (2), 65-71. 

Identifying molecular mechanisms of epileptogenesis will provide new targets for developing small molecules to prevent epilepsy 633... 

Epileptogenesis is the process by which a normal brain becomes epileptic. The very complexity of understanding mechanisms underlying the hyperexcitability of the epileptic brain has contributed to enhanced emphasis in attempts to prevent development of epilepsy, i.e. epileptogenesis. 

DeLorey, T. M., and Olsen, R. W. (1999) GABA and epileptogenesis comparing gabrb3 gene-deficient mice with Angelman syndrome in man. Epilepsy Res. 36, 123-132. 

Secondary Epileptogenesis, Kindling, and Intractable Epilepsy A Reappraisal from the Perspective of Neuronal Plasticity Thomas P. Sutula... 

An In Vitro Model of Stroke-Induced Epilepsy Elucidation of the Roles of Glutamate and Calcium in the Induction and Maintenance of Stroke-Induced Epileptogenesis Robert J. DeLorenzo, David A. Sun, Robert E. Blair, and Sompong Sambati... 

Evaluation of oc2A-ARD79N/D79Nmice in the kindling model of epilepsy revealed that these animals exhibited increased epileptogenesis coupled with an enhanced... 

Najm IM, Janigro D, Babb TL. Mechamisms of epileptogenesis and experimental models of seizures. In Wylie E, ed. The Treatment of Epilepsy, 3d ed. Philadelphia, Lippincott Williams Wilkins 2001 33-44. 

The study of epileptogenesis is critical for (a) identifying patients who are at risk of developing epilepsy and (b) targeting drugs that can modify the epileptogenic process and could therefore prevent the development of the disease. 

The prolonged latent period in people suggests that either epileptogenesis is a long process, or that a second insult is necessary for epilepsy to occur. This second hit hypothesis proposes that an initial insult results in lowered seizure threshold, and then a later insult, the second hit , results in the expression of epilepsy (Walker et al., 2002). 

Since the methods of modeling epilepsy are so diverse, it is imperative to select the most appropriate models for studying epileptogenesis. The most common methods of studying this process are in rodents (Table 6.1), in particular the kindling or post-SE models. 

The probability of SE patients subsequently developing epilepsy within 2 years is 41% compared with 13% of those with acute symptomatic seizures but no SE (Hesdorffer et al., 1998). This suggests a relationship between the prolonged seizures of SE and subsequent epileptogenesis, although a relationship between the length of seizure and the nature and severity of the precipitant cannot be discounted. 

Thus multifarious processes are involved in epileptogenesis, and this has complicated the identification of drugs that can be given in the latent period, which will prevent the later development of epilepsy. 

---