Theophylline reduces cerebral hyperaemia and enhances brain damage induced by seizures

Hippocampal and neocortical blood flows and tissue pO2 were investigated by mass spectrometry in unanaesthetized spontaneously breathing rats during kainic acid-induced seizures to determine whether adenosine is involved in the coupling of cerebral blood flow to metabolism during enhanced metabolic demand. The possible involvement of adenosine in the neuronal damage induced by seizures was also analyzed. The intrinsic effects of theophylline and the duration of the adenosine receptor blockade by this xanthine were first tested in 8 rats. Two groups of rats were then compared: one (n = 6) received kainic acid, and the other (n = 10) theophylline 15 min prior to kainic acid administration. An additional group of 10 rats was taken for classical histology 48 h after kainic acid treatment. Theophylline significantly reduced the hyperaemia observed during seizures, prevented any tissue hyperoxia and enhanced brain damage. This strongly suggests that adenosine is partly responsible for the increase in cerebral blood flow during kainic acid-induced seizures and has neuroprotective properties.