Circulation Research, Vol 47, 568-577, Copyright © 1980 by American Heart Association

ARTICLES

Changes in brain adenosine during bicuculline-induced seizures in rats. Effects of hypoxia and altered systemic blood pressure

HR Winn, JE Welsh, R Rubio and RM Berne

We analyzed brain tissue in 139 rats for adenosine and its metabolites, inosine and hypoxanthine, during the initial 120 seconds of seizures induced by bicuculline. We also measured ATP, ADP, AMP, phosphocreatine (PCr), and lactate. We divided the rats into four groups by adjustment of their preictal arterial oxygen tension: group I, PaO2 > 200 mm Hg; group II PaO2 = 50 mm Hg; and group III: PaO2 = 100 mm Hg. We treated a fourth group whose PaO2 = 100 mm Hg with phentolamine to block the 44% rise in blood pressure which occurred with the onset of seizures. PaCO2 was maintained between 30 anf 40 mm Hg in all groups. Brain tissue was sampled rapidly after 0, 10, 20, 30, 60, and 120 seconds of seizures by the freeze-blow technique. With normoxia (PaO2 = 100 mm Hg) or hyperoxia (PaO2 > 200 mm Hg), adenosine increased within ten seconds of the onset of seizures and remained elevated even after 120 seconds. Elevations in inosine and hypoxanthine were delayed compared to the increases in adenosine. A reduction in PaO2 (50 mm Hg) or systemic blood pressure during seizures caused a further augmentation in the increase in brain adenosine levels. During the seizure period, transient changes in adenine nucleotides and energy charge were observed, but PCr remained depressed and lactate continued to rise. The rapid and sustained increase in cerebral adenosine levels, temporally paralleling the changes in cerebral blood flow, supports the role for adenosine in the regulation of cerebral blood flow.

This article has been cited by other articles:

				T. Pearson, F. Nuritova, D. Caldwell, N. Dale, and B. G. Frenguelli A Depletable Pool of Adenosine in Area CA1 of the Rat Hippocampus J. Neurosci., April 1, 2001; 21(7): 2298 - 2307. [Abstract] [Full Text] [PDF]

				J. B. Wiesner, B. G. Ugarkar, A. J. Castellino, J. Barankiewicz, D. P. Dumas, H. E. Gruber, A. C. Foster, and M. D. Erion Adenosine Kinase Inhibitors as a Novel Approach to Anticonvulsant Therapy J. Pharmacol. Exp. Ther., June 1, 1999; 289(3): 1669 - 1677. [Abstract] [Full Text]

				R. J. DiGeronimo, C. A. Gegg, and S. L. Zuckerman Adenosine depletion alters postictal hypoxic cerebral vasodilation in the newborn pig Am J Physiol Heart Circ Physiol, May 1, 1998; 274(5): H1495 - H1501. [Abstract] [Full Text] [PDF]

				T. Porkka-Heiskanen, R. E. Strecker, M. Thakkar, A. A. Bjørkum, R. W. Greene, and R. W. McCarley Adenosine: A Mediator of the Sleep-Inducing Effects of Prolonged Wakefulness Science, May 23, 1997; 276(5316): 1265 - 1268. [Abstract] [Full Text]

				C.-J. Tseng, L.-P. Ger, H.-C. Lin, and C.-S. Tung Attenuated Cardiovascular Response to Adenosine in the Brain Stem Nuclei of Spontaneously Hypertensive Rats Hypertension, February 1, 1995; 25(2): 278 - 282. [Abstract] [Full Text]

				D. Rainnie, H. Grunze, R. McCarley, and R. Greene Adenosine inhibition of mesopontine cholinergic neurons: implications for EEG arousal Science, February 4, 1994; 263(5147): 689 - 692. [Abstract] [PDF]