The free radical scavenger alpha-phenyl-tert-butyl nitrone aggravates hippocampal apoptosis and learning deficits in experimental pneumococcal meningitis

The effect of adjuvant therapy with the radical scavenger alpha -phenyl-ter t-butyl nitrone (PBN; 100 mg/kg given intraperitoneally every 8 h for 5 day s) on brain injury and learning function was evaluated in an infant rat mod el of pneumococcal meningitis. Meningitis led to cortical necrotic injury ( median, 3.97% [range, 0%-38.9%] of the cortex), which was reduced to a medi an of 0% (range, 0%-30.9%) of the cortex (P <.001) by PBN. However, neurona l apoptosis in the hippocampal dentate gyrus was increased by PBN, compared with that by saline (median score, 1.15 [range, 0.04-1.73] vs. 0.31 [range , 0-0.92];). Learning function 3 weeks after cured infection, as assessed b y the Morris water maze, was decreased, compared with that in uninfected co ntrol animals (P<.001). Parallel to the increase in hippocampal apoptosis, PBN further impaired learning in infected animals, compared with that in sa line-treated animals (P<.02). These results contrast with those of an earli er study, in which PBN reduced cortical and hippocampal neuronal injury in group B streptococcal meningitis. Thus, in pneumococcal meningitis, antioxi dant therapy with PBN aggravates hippocampal injury and learning deficits.