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Investigation on the effect of fingolimod on epileptogenesis and cognitive impairments in adult rats following hypoxia-induced neonatal seizure
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Seyed Ahmad Najafian   , Yaghoob Farbood , Alireza Sarkaki , Samireh Ghafouri |
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Abstract: (264 Views) |
Introduction: Hypoxia-induced neonatal seizure (HINS) mainly leads to deleterious effects on brain function, especially cognitive impairments and increased susceptibility to epilepsy in later life. Early inflammation plays an important role in the pathology of these consequences. Therefore, we explored the long-term outcomes of Fingolimod (FTY720) treatment as an anti-inflammatory and neuroprotective agent in a rat model of HINS.
Methods and Materials: Seizures were induced in P10 rats by exposure to 5% O2 for 20 minutes.Sixty minutes after the onset of hypoxia, pups received FTY720 (0.3 mg.kg−1) or saline for 12 consecutive days (lactation period) and they were used at P60-P63 for behavioral tests, ELISA and Pentylenetetrazole (PTZ) kindling model.
Results: The results of OF, NOR and EPM tasks showed that, FTY720 prevent hippocampal memory dysfunction and anxiety-like behavior in both male and female hypoxic groups which was accompanied with decreased TNF-α in hippocampus. In addition, FTY720 postpone epileptogenesis just in female hypoxic+FTY group and decreased severity of seizures in both genders.
Conclution: Our results suggest, FTY720 treatment in immature rats prevent the long-lasting deficits, like increased inflammation, related cognitive impairments and decreased the severity of seizures in rats which previously subjected to HINS. In addition, FTY720 did not show significant interaction with gender in the most of experiments, except the average day to reach fully kindled state. Taken together, FTY720 has therapeutic potential for long lasting effects of HINS in both male and female animals at puberty.
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| Keywords: HINS, Fingolimod, Memory, Anxiety, Inflammation |
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Full-Text [PDF 326 kb]
(41 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/01/18 | Accepted: 2023/08/23 | Published: 2023/08/23
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