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Aminophylline aggravates long-term morphological and cognitive damages in status epilepticus in immature rats
Li-Tung Huang1, Chia-Wei Liou, San Nan Yang
1Department of Pediatrics, Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, Taiwan. huang_li@taiwan.com
Insights
Aminophylline, an apnea treatment, worsened seizures and brain damage in developing rats. Adenosine receptor antagonists may exacerbate seizure-induced injury in young brains.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Status epilepticus (SE) is a severe neurological condition.
- The developing brain's response to SE and potential drug interactions require further investigation.
- Aminophylline is an adenosine receptor antagonist used for apnea.
Purpose of the Study:
- To investigate the synergistic effects of aminophylline on status epilepticus in the developing brain.
- To determine if aminophylline exacerbates seizure-induced damage and cognitive deficits.
Main Methods:
- Rats were treated with saline, aminophylline, lithium-pilocarpine (Li-PC), or Li-PC plus aminophylline on postnatal day 14.
- Behavioral testing (Morris water maze) was conducted at P80.
- Histological analysis (cresyl violet and Timm stain) assessed brain lesions and mossy fiber sprouting.
Main Results:
- Aminophylline alone did not induce seizures.
- Both Li-PC and Li-PC plus aminophylline groups exhibited seizures.
- Aminophylline aggravated spatial memory deficits and histological brain damage in Li-PC-treated rats at adulthood.
Conclusions:
- Adenosine receptor antagonists, such as aminophylline, can exacerbate seizure-induced damage in the developing brain.
- These findings suggest caution when using aminophylline in contexts involving developing brains and seizure activity.
Abstract:
Here, we investigated whether aminophylline, an adenosine receptor antagonist used usually as a treatment for premature apnea, had synergistic effects on status epilepticus in the developing brain. On postnatal day 14 (P14), four groups of rats intraperitoneally received saline, aminophylline, lithium--pilocarpine (Li-PC), and Li-PC plus aminophylline, respectively. Subsequently, the Morris water maze task was performed at P80. The brains were then analyzed with cresyl violet stain for histological lesions and evaluated for mossy fiber sprouting with the Timm stain. No seizures were elicited in the saline-treated or aminophylline-treated rats. Both the Li-PC-treated and aminophylline plus Li-PC-treated rats exhibited seizures and there was no significant difference in mortality between the two groups. More interestingly, as in adulthood (P80), aminophylline aggravated the spatial deficits and histological damages seen in Li-PC-treated rats. In summary, this present study suggests that the use of adenosine receptor antagonists, such as aminophylline, exacerbates seizure-induced damage in the developing brain.