Epilepsy and neuroprotection: an illustrated review.
Multiple types of insults, such as status epilepticus, hypoxia and trauma, may alter the central nervous system. Strategies to protect the brain against insults remain a very difficult and challenging problem. Damage to the central nervous system can be modulated via excessive excitatory and reduced inhibitory neurotransmission. In addition, increased sodium and calcium loading through impaired voltage-sensitive channels, as well as alterations in the acid-base balance can contribute to both excitotoxic and apoptotic cell death. Epilepsy treatment has always been related to neuroprotection, since it aims to reduce the duration or totally suppress seizures. Although the debate on the capacity of simple seizures to induce neuronal injury is still ongoing, no doubt persists on the disastrous effects of prolonged episodes of status. The next step would be to prevent epilepsy. Several animal models have been used to study the various aspects of the epileptogenic process. In humans, one of the most compelling examples of a series of epileptogenic events is temporal lobe epilepsy (TLE). Temporal lobe epilepsy is often attributed to prolonged febrile convulsions in childhood resulting in mesial temporal sclerosis. However, the relationship between TLE, seizures in childhood and hippocampal sclerosis may not be apparent as initially believed. Furthermore, it is well recognized that in a number of patients there is a delay from a specific insult to the onset of seizures. This "latent period" could be an opportunity for effective intervention, provided that the underlying mechanisms are understood and that appropriate means for a beneficial modification of the disease process become available. The present review discusses the various steps of temporal lobe epilepsy and provides illustrations of the various mechanisms implicated in neuronal death. Data from animal models is also presented and illustrated with video sequences. Finally, on the basis of what is known on mechanisms of action of available antiepileptic drugs, some suggestions are put forward. Basic science and research are guided by clinical queries and from ongoing dialogue. The present illustrated review deals with only a small part of the important amount of work related to epilepsy and neuroprotection. As such it is necessarily schematic or even simplistic. The review is designed to inform clinicians about the basic issues related to the subject, thus allowing them to follow the ongoing debate and participate with pertinent questions. (Published with video sequences).
Arzimanoglou
Alexis
A
Epilepsy Unit, Child Neurology and Metabolic Diseases Departmentand INSERM E9935, University Hospital Robert-Debré, Paris, France. alexis.arzimanoglou@rdb.ap-hop-paris.fr
Hirsch
Edouard
E
Nehlig
Astrid
A
Castelnau
Pierre
P
Gressens
Pierre
P
Pereira de Vasconcelos
Anne
A
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis / Q000201:enzymology* / Q000503:physiopathology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D018079:Receptors, GABA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
D015220:Calcium Channels; D005609:Free Radicals; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D019001:Nitric Oxide Synthase