Aminophylline aggravates long-term morphological and cognitive damages in status epilepticus in immature rats.
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.
Huang
Li-Tung
LT
Department of Pediatrics, Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, Taiwan. huang_li@taiwan.com
Liou
Chia-Wei
CW
Yang
San Nan
SN
Lai
Ming-Chi
MC
Hung
Pi-Lien
PL
Wang
Tzu-Jou
TJ
Cheng
Shu-Chun
SC
Wu
Chia-Lu
CL
D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000628:Aminophylline / Q000633:toxicity*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D020439:Growth Cones / Q000187:drug effects / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology; D018020:Lithium Compounds / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000473:pathology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000633:toxicity*; D010862:Pilocarpine / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*
D018020:Lithium Compounds; D018721:Muscarinic Agonists; D010726:Phosphodiesterase Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D010862:Pilocarpine; D000628:Aminophylline