No abstract

For the systematic study of the role of inflammation in the morbidity and mortality associated with bacterial meningitis, techniques for quantitation of the inflammatory reaction in the meninges of rabbits with experimental pneumococcal infection were developed. The brains of 19 infected animals were removed intact, and the area of inflammation in microscopic sections was quantitated by an electronic X-Y plotter connected to a computer. Exudate was maximal along the ventral surface of the brain at the level of the cerebellum. Inflammation increased progressively with time and peaked at 72 hr. In a separate group of 29 animals, lactic acid dehydrogenase concentrations in cerebrospinal fluid increased significantly during infection, and the rate of increase wirh time coincided with the increase in inflammation documented histologically. The described method of quantitating inflammation in the meninges during experimental meningitis makes it possible to study the increase in granulocyte involvement with time. The establishment of a direct relation between the concentration of lactic acid dehydrogenase in the cerebrospinal fluid and the inflammatory mass validates the use of lactic acid dehydrogenase as an indicator of inflammation.

Prior to 1930, experimental models of pneumococcal meningitis employing monkeys and cats were described (1-3), but in recent years only a dog model has been reported in detail (4, 5). Experimental infection in rabbits heretofore has been unsuccessful (6).The present study was undertaken to develop and characterize a reproducible, inexpensive and convenient model of pnueumococcal meningitis in rabbits. Such a model can be used in the study of basic processes responsible for the morbidity and mortality associated with bacterial meningitis.Materials and Methods. Animals and method of inducing meningitis. New Zealand white rabbits weighing between 2.5 and 3.2 kg were employed. All rabbits were anesthetized with pentobarbital given intravenously, and in 22 animals (Group I ) , 0.5 ml of cerebrospinal fluid (CSF) was removed from the basal cistern according to the technique of ChaImars and Wurtman (7). Within 2 min of cisternal puncture, 1 ml of a saline suspension containing I O7 colony forming units/ ml (cfu/ml) of pneumococci was injected into a marginal ear vein. Five min later, blood for quantitative culture was obtained from the opposite ear. An additional 53 rabbits (Group 11) were infected similarly, except that the CSF withdrawn from the cistern was replaced with 0.5 ml of a sterile 0.125% suspension of mucin (Sigma Chemical Co., St. Louis, Mo. )in Ringer's lactate adjusted to pH 7.34. All animals were followed to spontaneous death; 2 animals in Group I1 died from excess anesthesia and were excluded from subsequent analyses. CSF and blood were obtained a t 24-48 hr intervals.Six control animals served as non-infected mucin controls. Each received 0.5 ml of a 0.1 2 5% suspension of mucin intracisternally, and was sacrificed 72 hr later. Blood and CSF were obtained at 24 hr intervals. A normal animal served as a control for histological purposes.