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Adenosine is an endogenous modulator that has an inhibitory effect on neuronal activity. The aim of this work was to investigate the role of aminophylline, an adenosine receptor antagonist, on the long-term effects of status epilepticus (SE) in the developing brain. Four groups of rats at the postnatal age of 12 days were intraperitoneally administered with saline, aminophylline (50 mg/kg), lithium-pilocarpine (Li-PC) (3 mEq/kg-60 mg/kg), and Li-PC plus aminophylline, respectively. The four groups were tested for spatial memory using the Morris water maze task at P80 and motor performance by the Rotarod test at P100. The brains were then analyzed with cresyl violet stain for histological lesions and evaluated for mossy fiber sprouting with the Timm stain. At the acute stage, all rats subjected to Li-PC developed SE and no seizures were elicited in the saline-treated or aminophylline-treated rats. The seizure duration was longer in the Li-PC plus aminophylline group (346.9+/-32.7 min) as compared with that in the Li-PC group (265.2+/-9.8 min). The difference of mortality was not significant. Rats without seizures exhibited no motor imbalance, spatial deficits, or morphological changes. The rats with Li-PC-induced SE demonstrated spatial memory deficits without motor incoordination or morphological changes. However, the rats subjected to Li-PC plus aminophylline exhibited motor impairment and morphological changes, including neuronal cell loss in CA1 area and increased mossy fiber sprouting in CA3 area. In addition, the rats of Li-PC plus aminophylline had greater spatial memory deficits than that seen in rats with Li-PC. We concluded that an adenosine receptor antagonist, such as aminophylline, had synergistic effects on the SE-induced long-term deficit of cognition and motor performance in the developing brain. The present study may provide experimental evidence and lead to novel therapeutic interventions.

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.