NITRIC-OXIDE CONCENTRATIONS AND CEREBROSPINAL-FLUID PARAMETERS IN AN EXPERIMENTAL ANIMAL-MODEL OF STREPTOCOCCUS-PNEUMONIAE MENINGITIS

Streptococcus pneumoniae is a common cause of meningitis. Nitric oxide (NO) has been implicated in causing cerebral edema. Modulating NO pro duction in cerebrospinal fluid (CSF) may have a role in the treatment of bacterial meningitis. Experimental S. pneumoniae meningitis was ind uced in a rabbit model to determine CSF parameters and NO concentratio ns. An electrochemical probe in the CSF throughout the 7-hour experime nt monitored NO concentrations. The animals had S. pneumoniae (10(5)) injected intracisternally and incubated for 1 hour. Cerebrospinal flui d 200-300 yl was obtained by intracisternal puncture at zero, 2, 4, an d 7 hours after drug administration to measure glucose, protein, and l actic acid by standard chemical methods. White blood cell count was me asured by hemocytometry. Three groups of five animals were used-contro l (C), ceftriaxone (CTX), and ceftriaxone plus dexamethasone (CTX+D). Ceftriaxone concentrations in CSF were obtained by microdialysis and a nalyzed by high-performance liquid chromatography. Mean (+/- SEM) CSF white blood cell count was significantly higher at 2 hours in the C gr oup than in the other two groups (C 7307 +/- 1302, CTX 605 +/- 345, CT X+D 730 +/- 43/mm(3), p<0.002). Ceftriaxone induced a significant rise in protein at 4 hours compared with the other groups (C 364 +/- 107, CTX 1158 +/- 797, CTX+D 365 +/- 100 mg/dl, p<0.02). Cerebrospinal flui d lactic acid was significantly different at 4 and 7 hours between C a nd CTX+D groups (4-hr C 8.0 +/- 2.2, CTX+D 2.0 +/- 0.4 mmol/L, p<0.05; 7-hr C 10.2 +/- 2.4, CTX+D 2.8 +/- 0.8 mmol/L, p<0.01). Median NO con centrations were significantly elevated in the control group compared with the other two groups (C 11.7, CTX 6.8, CTX+D 6.5 mu M, p<0.02 C v s CTX, p<0.01 C vs CTX+D). Average (+/- SEM) NO concentrations were si gnificantly higher in the C group at 4 hours (18.1 +/- 0.4, CTX 5.8 +/ - 1.8 mu M, p<0.05; CTX+D 11.5 +/- 4.0 mu M, p>0.05), whereas they did not rise significantly until 7 hours in the CTX group (CTX 18.7 +/- 0 .7, C 8.9 +/- 0.4 mu M, p=0.055; CTX+D 8.1 +/- 2.2 mu M, p<0.05). Thes e results indicate that ceftriaxone with or without dexamethasone sign ificantly decreases lactic acid concentrations and white cell penetrat ion into the CSF in an experimental model of S. pneumoniae meningitis. In addition, ceftriaxone induced a significant elevation in CSF prote in. Median NO production in the CSF was significantly attenuated by ce ftriaxone.