Objective: 

Maternal systemic hypotension associated with fetal hypoxia/ischemia may cause impaired spatial learning and memory. Topiramate, an antiepileptic drug, exhibited neuroprotective effects in animal models of hypoxia/ischemia, excitotoxic insults and stroke. Therefore, we investigated water maze performances of 70-day-old rats to explore the possible favorable effects of topiramate against the outcomes of maternal systemic hypotension-induced neuronal damage.

Methods: 

Pregnant Wistar rats were assigned to control (n=7), control+topiramate (n=5), hypotension (n=3), hypotension+topiramate (n=6) groups. Hypotension groups were subjected to transient systemic hypotension by blood withdrawal for 30 minutes on the 15th day of pregnancy. Randomly selected animals were injected intraperitoneally with topiramate (40 mg/kg/day) or saline 15 minutes after the termination of the hypotensive period. After spontaneous vaginal delivery, cognitive functions of pups were evaluated via Morris water maze test on postnatal day 70. The latency to reach the platform (seconds) and percentage of the time spent in the target quadrant were measured. Data were analyzed statistically.

Results: 

Morris water maze performances improved in all groups over time (P<0.05, 1st vs. 5th day). Animals in the hypotension group took longer time to reach the hidden platform (P>0.05) and spent significantly less time in the target quadrant in comparison with other groups. Both parameters were improved with topiramate treatment (P<0.05).

Conclusions: 

Since topiramate treatment immediately after hypoxic-ischemic insult significantly improved long-term cognitive functions, it may offer a therapeutic potential for neuroprotection over a prolonged period in the developing rat brain.