Abstracts

RATIONALE: Status epilepticus (SE) has a high mortality and morbidity rate in children. In children who survive SE disturbances in learning and memory are frequent sequelae. There is increasing evidence that enriching the environment can improve cognitive and motor deficits following a variety of brain injuries. The goal of this study was to determine whether the environment in which animals are raised influences cognitive function following SE.
METHODS: Rats underwent lihium-pilocarpine-induced SE at postnatal (P) day 20. Following SE animals were randomly assigned to either an enriched environment or standard vivarium care for 28 days. Assessments of neurogenesis using bromodeoxyuridine (BrdU) analysis and pCREB immunostaining were made at two time points during the enriched environment phase of the study: P29 when the rats had been exposed to the enriched or non-enriched environment for nine days; and P49, the last day in the environment. The animals were tested in the water maze from P50-P55. BrdU analysis and pCREB immunostaining were made at two time points during the water maze testing: P51 following one day of testing; and P55, following completion of the probe test.
RESULTS: While both the enriched and non-enriched showed reductions in escape latencies over four days of testing (F(3,46)=6.007; p=0.002), the enriched group performed significantly better than the non-enriched group in the water maze (F(1,20)=5.5203; p=0.029). In addition, the enriched group spent more time in the target quadrant during the probe test than the controls (t=2.751; p=0.012). No differences were noted in the swimming speed in the two groups (t=0.445, p=0.660 ). There was a significantly increased number of BrdU-labeled cells in the animals raised in the enriched environment at P29 (t=3.041; p=0.038), but not at the other time points. To determine the identity of the BrdU-labeled cells, sections from both enriched and non-enriched sacrificed at P29 underwent fluorescence double-label immunohistochemistry. In both the enriched and non-enriched groups the majority of BrdU-labeled nuclei in the dentate granule cell layer exhibited co-localization with NeuN (enriched 233/332 [70.2%]; non-enriched 169/211 [80.1%]; Chi square =0.474, p=0.491). A significant increase in pCREB immunostained cells was found in animals exposed to the enriched environment at P29 (t=3.315; p=0.030); P49 (3.834; p=0.018), and P51 (t=4.060; p=0.015) but not at P55 (p[gt]0.05).
CONCLUSIONS: This study demonstrates that exposure to an enriched environment following SE in weanling rats significantly improves cognitive function. The increased neurogenesis and activation of transcription factors associated with the enriched environment likely contributes to this enhanced visual-spatial memory.
At the end of this presentation participants should be able to understand the importance of environmental stimulation following status epilepticus.
[Supported by: A Mental Retardation Research Center grant from NIH (2P30HD18655) and a grant from the NINDS (NS27984) to GLH.]