Experimental Studies on Cerebral Metabolic Alterations Induced by Penicillin.

Shin, Kyu Man; Chu, Jeong Wha

Original Article

Journal of Korean Neurosurgical Society 1981;10(1): 27-38.

¹Department of Neurosurgery, College of Medicine, Korea University, Seoul, Korea.
²Department of Neurosurgery, College of Medicine, Ewha Womans University, Seoul, Korea.

ABSTRACT

It has been postulated that central nervous system disorders characterized by convulsive seizures are caused by alterations in one or more cerebral metabolism especially in cellular energy metabolism, electrolyte metabolism and glutamate metabolism. In the present study, alterations in cerebral energy metabolism, cellular electrolyte metabolism and glutamate metabolism were studied to investigate biochemical nature of cerebral disturbances in rats injected intraperitoneally with massive doses of penicillin. Also carried out were in vitro experiments by which direct effects of penicillin on concentrations of high energy compounds and Na+, K+-ATPase activity in the brains were determined. Intraperitoneal injections of pencillin G sodium(1,000,000 I.U. per kg body weight) to rats twice daily for 3 to 5 days resulted in significant decreases in cerebral concentrations of ATP, phosphocreatine and lactate, suggesting that penicillin induces cerebral dysfunctions by inhibiting energy production. While cerebral Na+, K+-ATPase activity and brain K+ content were significantly decreased in rats with penicllin-induced cerebral dysfunctions, brain Na+ and water contents were significantly increased. Observations that, in rats with penicillin-induced cerebral dysfunctions, the fall in high-energy phosphate contents in the brain took place as rapidly as the cation shifts indicate that alterations in both energy metabolism and electrolyte metabolism in the brain may be responsible for cerebral dysfunctions induced by penicillin. These assumptions were further supported by the findings that Na+, K+-ATPase activity and high-energy phosphate contents in the isolated cerebral hemispheres were profoundly affected by the addition of penicillin to the medium in which in vitro experiment was carried out. While the activity of glutamine synthetase in the brain was increased in rats exhibiting cerebral dysfunctions induced by penicillin, the activity of glutamine dehydrogenase was significantly decreased. Significance of changes in activities of these two brain enzymes in penicillin-induced cerebral dysfunctions was not immediately understood. It may be possible, however, that penicillin may influence glutamate contents in the brain directly orindirectly through the alteration of these two brain enzyme activities so as to modify the cerebral functions.