Neuroprotective Strategies in Epilepsy

Binder DK (2004) The role of BDNF in epilepsy and other diseases of the mature nervous system. Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: Evidence for anterograde axonal transport. Hippocampal long-term potentiation is supported by presynaptic and postsynaptic tyrosine receptor kinase B-mediated phospholipase Cg signaling. Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS. What is the biological significance of BDNF mRNA targeting in the dendrites? Clues from epilepsy and cortical development. Introduction From the earliest attempts to develop treatments for epilepsy, the primary goal of epilepsy therapeutics has been seizure control. Since seizures are not only patho-gnomonic for epilepsy, but also represent a significant problem for patients, this strategy has been both rational and fruitful. However, in spite of the development of a wide array of anticonvulsant drugs, some patients have poorly controlled seizures while many more report breakthrough seizures. Efforts to seek better anticonvulsant treatments are ongoing, and these efforts have been accompanied by a concurrent effort to protect the brain from the damaging effects of seizures. Using animal models, epilepsy researchers have discovered that seizures lead to permanent changes in the brain circuitry. Some of these changes, such as mossy fiber sprouting, could potentially be associated with seizure progression. In addition, uncontrolled seizures may cause a loss of brain cells. Humans with chronic temporal lobe epilepsy (TLE) show neuronal loss, sclerosis, and atrophy , especially in the hippocampus. In animal models, the occurrence of severe seizures leads to cell loss in various regions of the brain, especially the limbic system. As illustrated in Figure 1, the hippocampus of rodents has proved to be exquisitely sensitive to the excitotoxic cell death induced by seizures, and this cell loss in the animal model reflects the damage profile seen in human TLE. Behavioral studies in animals have also shown that seizure-related cell loss is associated with functional impairments, such as memory decline and emotional deficits , similar to findings in humans where epilepsy has been associated with functional impairments ranging from memory loss to alterations in mood. Protecting neu-rons in the human epileptic brain may protect against functional impairments. As a consequence of the realization that seizures beget neuronal loss and behavioral impairment, epilepsy researchers are increasingly interested in pursuing neuropro-tective strategies in epilepsy. Protecting neurons from death or functional compromise after seizures …