Abstracts

Rationale: Hypoxia at P10 is associated with later long term impairments in memory and behavior. Topiramate (TPM) has been shown to be neuroprotective in many models of hypoxia-ischemia. Our goal was to investigate if continuous topiramate therapy during early stages of development has long term effects on memory and behavior and whether it prevents the long term impairments in memory and behavior resulting from an acute hypoxic injury in P10 rat pups. Methods: Four groups of rats were studied. Group1: control group injected daily with PBS from P0-P21. Group2: control group injected with topiramate (30mg/kg every 24h, i.p.) from P0-P21. Group3: acute hypoxia group injected daily with PBS from P0-P21 and subjected to acute hypoxia for 20 min down to 4% on P10. Group4: acute hypoxia group injected with topiramate from P0-P21, similar to group 2, and subjected to acute hypoxia at P10, similar to group 3. Handling test for aggression (Kruskal Wallis test) and Morris water maze test (ANOVA, multiple groups with repeated measures with post hoc LSD analysis) for memory were performed starting P81. Results: The handling test scores showed increase aggressivity in the Acute group (mean±SE 22.1±0.89) as compared to the control+PBS (19.69±0.94) and to Acute+ TPM (19.38±0.76) groups (p=0.048 and p=0.018 respectively). Acute+ TPM group was not different from the control+PBS or control + TPM (18.23±1.4) groups (p=0.7 and 0.78 respectively). Morris water maze test (F=11.67 p=0.002) showed that Acute group (time to reach platform for days 1, 2, 3, and 4 were 471±33, 411±40, 342± 48, 292± 45 seconds respectively) had long term memory impairment as compared to the control+PBS group (359±40, 375±55, 318±50, 219±55) and to the Acute+ TPM group (388±32, 294±35, 222±35, 244±42) (p=0.048 and 0.001 respectively). The Acute+ TPM group was not different from control+PBS or control+ TPM (365±54, 274±48, 251±44, 182±40) groups (p=0.313 and p=0.532 respectively). Conclusions: Continuous topiramate therapy in the developing brain did not have long term detrimental effects on behavior or memory, but did prevent the long term consequences of an acute hypoxic insult on these functions.