The Role of Postictal Hypoxia in Seizure-Induced Neurogenesis, Dentate Gyrus Area and Ectopic Migration of Granule Cells

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Background: Adult neurogenesis is influenced by several external factors such as exercise, enrichment, and seizures. The mechanism behind seizure-induced neurogenesis, however, is unknown. Following seizures, a phenomenon known as postictal severe hypoxia occurs in areas localized to seizure activity. Hippocampal oxygen levels drop from the normoxic range of 18-30mmHg below the severe hypoxic threshold of 10mmHg. This can be prevented with the pre-administration of a COX inhibitor (ibuprofen) or L-type calcium blocker (nifedipine). We hypothesized that the postictal hypoxia phenomenon would result in increased neurogenesis and alter the migration pattern of newborn granule cells causing them to ectopically migrate into the hilus. Methods: Electrical kindling was utilized to elicit hippocampal seizures in rats. An oxygen sensing probe and a bipolar electrode to elicit and record seizures were implanted ipsilaterally into the dorsal and ventral hippocampus, respectively. Rats were separated into a no seizure and seizure group. Rats undergoing kindling were administered DMSO, 20mg/kg ibuprofen, or 15mg/kg nifedipine 30 minutes prior to each session while rats without seizures were handled identically. All rats were perfused following 30 kindling or control sessions. Cryostat sections of 40μm were taken and labelled for doublecortin (DCX). DCX expressing cells were analyzed using confocal microscopy. Results: Seizures with hypoxia increased the total number of DCX expressing cells by 90%. Seizures with attenuated hypoxia via ibuprofen or nifedipine did not prevent the increase in neurogenesis following kindled seizures. Dentate gyrus area was significantly increased with seizures except when treated with nifedipine. The density of DCX cells was increased with seizure activity and was unaffected by hypoxia, though nifedipine treated rats had a higher increase in density following seizures. Lastly, the ectopic migration of cells into the hilus was also increased with seizure activity independent of hypoxia. Conclusion: Postictal hypoxia is not the underlying mechanism in seizure-induced neurogenesis, the increase in dentate gyrus area and the ectopic migration of cells into the hilus. It is the seizure activity driving these phenomena.
Seizures, Epilepsy, Postictal, Hypoxia, Neurogenesis, Ectopic
Addo-Osafo, K. (2020). The Role of Postictal Hypoxia in Seizure-Induced Neurogenesis, Dentate Gyrus Area and Ectopic Migration of Granule Cells (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from