Neuroprotection in epilepsy.
Neuroprotection following status epilepticus should encompass not only the prevention of neuronal death, but also preservation of neuronal and network function. This is critical because these aims are not necessarily equivalent; prevention of neuronal loss, for example, does not inevitably prevent epileptogenesis. There are endogenous neuroprotective mechanisms that can serve dichotomous roles (e.g. ERK 1/2 activation can result in either neuroprotection or promote neuronal death). The roles of potential endogenous mechanisms can depend upon the pattern and timing of their activation. The simplest exogenous neuroprotective mechanism is to halt seizure activity. Other approaches consist of early NMDA receptor antagonism or later inhibition of apoptotic pathways. The problem with the latter approach is that calcium accumulation results in the activation of a number of downstream pathways, the importance of which varies from region to region and in a cell-type specific manner. Neuroprotection in epilepsy is not a straightforward concept, and we need to be clear about our eventual objectives (e.g. preventing cognitive decline). There are numerous possible approaches to neuroprotection, and the efficacy of these depends upon their timing, the specific aims and even the method of status epilepticus induction.
Walker
Matthew
M
Department of Clinical & Experimental Epilepsy, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Box 29, Queen Square, London WC1N 3BG, UK. m.walker@ion.ucl.ac.uk
D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000503:physiopathology / Q000517:prevention & control; D004827:Epilepsy / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D013226:Status Epilepticus / Q000503:physiopathology / Q000517:prevention & control* / Q000628:therapy*
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate