The role of cytokines and growth factors in seizures and their sequelae

Although the neuropathological changes caused by severe or repeated seizure s have been well characterized, many questions about the molecular mechanis ms involved remain unanswered. Neuronal cell death, reactive gliosis, enhan ced neurogenesis, and axonal sprouting are four of the best-studied sequela e of seizures. In vitro, each of these pathological processes can be substa ntially influenced by soluble protein factors, including neurotrophins, cyt okines, and growth factors, Furthermore, many of these proteins and their r eceptors are expressed in the adult brain and are up-regulated in response to neuronal activity and injury. We review the evidence that these intercel lular signaling proteins regulate seizure activity as well as subsequent pa thology in vivo. As nerve growth factor and brain derived neurotrophic fact or are the best-studied proteins of this class, we begin by discussing the evidence linking these neurotrophins to epilepsy and seizure. More than a d ozen additional cytokines, growth factors, and neurotrophins that have been examined in the context of epilepsy models are then considered. We discuss the effect of seizure on expression of cytokines and growth factors, and e xplore the regulation of seizure development and aftermath by exogenous app lication or antagonist perturbation of these proteins. The experimental evi dence supports a role for these factors in each aspect of seizure and patho logy, and suggests potential targets for future therapeutics. (C) 2000 Else vier Science Ltd, All rights reserved.