Environmental Factors Influence Neurogenesis and Modify the Cognitive Outcome after Status Epilepticus.

Abstract

Memory Impairment Following Status Epilepticus in Immature Rats: Time-Course and Environmental Effects Rutten A, Van Albada M, Silveira DC, Cha BH, Liu X, Hu YN, Cilio MR, Holmes GL Eur J Neurosci 2002;16:501–513 Status epilepticus (SE) has a high mortality and morbidity rate in children. Disturbances in learning and memory are frequently associated with SE, although it is not clear when the cognitive deficits occur. If cognitive dysfunction occurs immediately after the seizure, the window of opportunity for therapeutic intervention is limited. The first goal of this study was to determine the timing of cognitive dysfunction after SE in weanling rats. As there is evidence that enriching the environment can improve cognitive and motor deficits after brain injury, our second goal was to determine whether environmental enrichment improves cognitive function after SE. Rats underwent lithium-pilocarpine–induced SE at postnatal (P) day 20 and were then tested for visual–spatial memory in the water maze at P22, P25, P30, or P50. Rats with SE performed significantly worse in the water maze than did control rats at all time points. Once the time courses of visual–spatial memory deficits were determined, a second group of P20 rats were subjected to SE and were then placed in an enriched environment (enriched group) or remained in standard cages in the vivarium (nonenriched group) for 28 days. After environmental manipulation, the animals were tested in the water maze. Rats housed in an enriched environment after the SE performed substantially better in the water maze than did rats housed in standard cages. However, no differences were found between the enriched and nonenriched groups in EEG or histologic evaluation. Although SE results in cognitive impairment within days of the seizure, housing in an enriched environment after SE has a beneficial effect on cognitive performance in rats. Delayed Kindling Epileptogenesis and Increased Neurogenesis in Adult Rats Housed in an Enriched Environment Auvergne R, Lere C, El Bahh B, Arthaud S, Lespinet V, Rougier A, Le Gal La Salle G Brain Res 2002;954:277–285 Environmental risk factors such as stressful experiences have long been recognized to affect seizure susceptibility, but little attention has been paid to the potential effects of improving housing conditions. In this study, we investigated the influence of an enriched environment on epileptogenesis. Epileptic susceptibility was assessed in animals housed in an enriched environment either before or during (group I) or only during (group II) a kindling procedure and in animals placed in isolated conditions (group III). The kindling paradigm provides a reliable assessment of the capacity to develop seizures after repeated daily low-frequency electrical stimulations. As both enriched environment and seizures are known to interfere with hippocampal neurogenesis, the number of newly generated dentate cells was assessed before and after the kindling procedure to investigate in more detail the relation between epileptogenesis and neurogenesis. We found that susceptibility to developing epilepsy differed in animals housed in complex enriched environments and in those housed in isolated conditions. Kindling epileptogenesis occurred significantly later in animals housed in enriched conditions throughout the procedure (group I) than in animals from groups II and III. We also demonstrated that cells generated during kindling survived for at least 42 days and that these cells were more numerous on both sides of the brain after environmental enrichment than in rats housed in isolated conditions. As similar values were obtained regardless of the duration of the period of enrichment, these cellular changes may not play a major role in delaying kindling development. We suggest that the increase response in neurogenesis after seizures may be an adaptive rather than epileptogenic response.