rwj-333369 and Epilepsy--Temporal-Lobe

Temporal Lobe Epilepsy (TLE) is a chronic condition characterized by epileptic seizures originating mainly in temporal lobe areas. Epileptogenesis is a process in which a central nervous system injury can lead surviving neuronal populations to generate abnormal, synchronous and recurrent epileptiform discharges producing focal or generalized seizures. Hipocampal sclerosis, a massive cell death in the hippocampal formation and in the other regions of temporal lobe, is considered as hallmark of TLE. Despite the numerous antiepileptic drugs (AEDs) commercially available, about 30-40% of patients remain with seizures refractory to pharmacological treatment. In addition, there is no drug with significant efficacy to modify the epileptogenesis process. In this review we present some data regarding the neuroprotective effect of some adenosinergic agents, erythropoietin and carisbamate regarding the disease- and epileptogenesis-modifying effect.

Topics: Anticonvulsants; Carbamates; Epilepsy, Temporal Lobe; Erythropoietin; Humans; Neuroprotective Agents; Purinergic P1 Receptor Agonists

Temporal lobe epilepsy is a relatively frequent, invalidating, and often refractory neurologic disorder. It is associated with cognitive impairments that affect memory and executive functions. In the rat lithium-pilocarpine temporal lobe epilepsy model, memory impairment and anxiety disorder are classically reported. Here we evaluated sustained visual attention in this model of epilepsy, a function not frequently explored.. Thirty-five Sprague-Dawley rats were subjected to lithium-pilocarpine status epilepticus. Twenty of them received a carisbamate treatment for 7 days, starting 1 h after status epilepticus onset. Twelve controls received lithium and saline. Five months later, attention was assessed in the five-choice serial reaction time task, a task that tests visual attention and inhibitory control (impulsivity/compulsivity). Neuronal counting was performed in brain regions of interest to the functions studied (hippocampus, prefrontal cortex, nucleus basalis magnocellularis, and pedunculopontine tegmental nucleus).. Lithium-pilocarpine rats developed motor seizures. When they were able to learn the task, they exhibited attention impairment and a tendency toward impulsivity and compulsivity. These disturbances occurred in the absence of neuronal loss in structures classically related to attentional performance, although they seemed to better correlate with neuronal loss in hippocampus. Globally, rats that received carisbamate and developed motor seizures were as impaired as untreated rats, whereas those that did not develop overt motor seizures performed like controls, despite evidence for hippocampal damage.. This study shows that attention deficits reported by patients with temporal lobe epilepsy can be observed in the lithium-pilocarpine model. Carisbamate prevents the occurrence of motor seizures, attention impairment, impulsivity, and compulsivity in a subpopulation of neuroprotected rats.

Topics: Animals; Anticonvulsants; Attention; Brain; Brain Mapping; Carbamates; Cell Count; Disease Models, Animal; Epilepsy, Complex Partial; Epilepsy, Temporal Lobe; Executive Function; Inhibition, Psychological; Lithium Carbonate; Neurons; Pattern Recognition, Visual; Pilocarpine; Rats; Rats, Sprague-Dawley; Reaction Time; Serial Learning; Status Epilepticus