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Published on: February 27, 2018
Long-term behavioral deficits following pilocarpine seizures in immature rats
1Department of Neurology, Harvard Medical School, Children's Hospital, Boston, MA 02115.
Insights
Early-life seizures in rats can lead to long-term behavioral changes and learning deficits, with effects varying significantly based on the age of seizure onset. Immature rats experiencing seizures showed lasting impacts.
Area of Science:
- Neuroscience
- Developmental Biology
- Behavioral Science
Background:
- Seizures during early brain development can have lasting consequences.
- Understanding age-dependent effects of seizures is crucial for predicting long-term outcomes.
Purpose of the Study:
- To investigate the long-term behavioral effects of induced seizures in immature rats at different developmental stages.
- To determine if early-life seizures cause persistent neurological and behavioral deficits.
Main Methods:
- Induced seizures using pilocarpine in 20-day-old (P20) and 45-day-old (P45) rats.
- Assessed long-term behavior, learning (water maze), seizure susceptibility (flurothyl), and hippocampal histology.
Main Results:
- P45 rats developed spontaneous recurrent seizures, aggression, hyperactivity, learning deficits, and hippocampal CA3 cell loss.
- P20 rats, despite more severe initial seizures, showed no recurrent seizures or significant histological damage, but exhibited mild learning impairments.
- Behavioral deficits were more pronounced in P45 rats compared to P20 rats.
Conclusions:
- Prolonged seizures in immature rats can induce age-dependent long-term behavioral deficits.
- The developing brain's vulnerability to seizure-induced damage and subsequent behavioral changes is critically dependent on age.
Abstract:
The effect of seizures on subsequent long-term behavior was studied in immature rats. A similar severity of seizures were induced in 20-day old rats (P20) and 45-day old rats (P45) by intraperitoneal injections of pilocarpine at doses of 200 mg/kg and 380 mg/kg, respectively. Immediately after injection of pilocarpine, prolonged seizures with electroencephalographic ictal discharges were observed in both groups of rats. These seizures were followed by seemingly complete neurological recovery. In rats that received pilocarpine at P45 spontaneous recurrent seizures appeared after 4-10 days and persisted until completion of the study at P100. Behavioral tests performed when the rats were fully mature demonstrated that they were more aggressive when handled, more active in open field, and had deficits in learning platform position in the water maze as compared to controls. Furthermore, flurothyl seizure latency was significantly lower in pilocarpine-treated P45 rats than controls. Histology examination showed gross cell loss in the CA3 subfield of the hippocampus in four out of six pilocarpine-treated rats while no cell loss was found in control rats. Rats that received pilocarpine at P20, despite having more severe seizures than the P45 rats, had no histological lesions, did not develop spontaneous recurrent seizures, and had no significant difference in the flurothyl seizure latency test when compared to their controls. While there was no difference between the control and pilocarpine-treated rats in the handling and open field test, P20 rats receiving pilocarpine were slower in learning platform position in the water maze than the controls. Rats receiving pilocarpine at P45 performed significantly more poorly than rats treated at P20 in the water maze. These results suggest that prolonged seizures in immature rats can cause long-term behavioral deficits. However, the severity and nature of these deficits are highly age dependent.
