Experimental Pneumococcal Meningitis. II. Characterization and Quantitation of the Inflammatory Process

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.

Influence of Granulocytes on Brain Edema, Intracranial Pressure, and Cerebrospinal Fluid Concentrations of Lactate and Protein in Experimental Meningitis

“…The statistical significance of this difference has not been determined. McAllister et al [21] observed an association between the maximal inflammation in CSF and the time of death in rabbits with experimental pneumococcal meningitis. Extensive work by Fishman et al [23], Chan and Fishman [24], and Chan et al [25] has implicated granulocytes as an important factor in development of brain edema.…”

“…In animal studies the time of death is associated with maximal inflammation in the subarachnoidal space [21], and one study suggested that neutropenic dogs with pneumococcal meningitis may survive longer than animals with a normal inflammatory reaction in the CSF [22]. Fishman et al [23], Chan and Fishman [24], and Chan et al [25] have demonstrated that products of leukocytes, such as polyunsaturated fatty acids and oxygen-free radicals, can induce brain edema, increased lactate production, and energy depletion in cortical brain slices of rats.…”

Nonsteroidal Anti-Inflammatory Agents in the Therapy for Experimental Pneumococcal Meningitis

“…The mortality from pneumococcal meningitis is directly correlated with the amount of meningeal inflammation [1]. Two parameters used to quantitate the inflammatory response are the density of CSF leukocytes and the protein concentration, both of which are increased during natural infection.…”

“…The morbidity and mortality associated with pneumococcal meningitis is directly proportional to the amount of inflammation in the subarachnoid space [1]. Much of the inflammatory response to the pneumococcus arises from the triggering of local host defenses by the pneumococcal cell surface, particularly the cell wall, which underlies the capsule [2,3].…”

The Relative Role of Bacterial Cell Wall and Capsule in the Induction of Inflammation in Pneumococcal Meningitis

“…The potential clinical relevance of the CSF response to cell wall material rests on the correlation between the clinical outcome of meningitis and the degree of inflammation [23]. Pneumococcal cell wall components are released into the surrounding medium during stationary-phase autolysis and, perhaps more importantly, during treatment of pneumococci with fJ-Iactam antibiotics.…”