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-tert-butyl nitrone (PBN; 100 mg/kg given intraperitoneally every 8 h for 5 days) on brain injury and learning function was evaluated in an infant rat model of pneumococcal meningitis. Meningitis led to cortical necrotic injury (median, 3.97% [range, 0%-38.9%] of the cortex), which was reduced to a median of 0% (range, 0%-30.9%) of the cortex (P<.001) by PBN. However, neuronal 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]; P<.001). Learning function 3 weeks after cured infection, as assessed by the Morris water maze, was decreased, compared with that in uninfected control animals (P<.001). Parallel to the increase in hippocampal apoptosis, PBN further impaired learning in infected animals, compared with that in saline-treated animals (P<.02). These results contrast with those of an earlier study, in which PBN reduced cortical and hippocampal neuronal injury in group B streptococcal meningitis. Thus, in pneumococcal meningitis, antioxidant therapy with PBN aggravates hippocampal injury and learning deficits.
Loeffler
J M
JM
Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
Ringer
R
R
Hablützel
M
M
Täuber
M G
MG
Leib
S L
SL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002540:Cerebral Cortex / Q000473:pathology; D003497:Cyclic N-Oxides; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D018782:Maze Learning / Q000187:drug effects; D008586:Meningitis, Pneumococcal / Q000473:pathology* / Q000523:psychology; D009474:Neurons / Q000473:pathology; D009589:Nitrogen Oxides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013296:Streptococcus pneumoniae / Q000302:isolation & purification
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone