Caspases inhibition decreases neurological sequelae in meningitis.
OBJECTIVE
To evaluate the effects of sustained caspase inhibition during the acute phase of meningitis-induced brain injury. Changes in neurobehavioral performance were the primary outcome variables.


METHODS
Randomized prospective animal study.


METHODS
University research laboratory.


METHODS
Male Wistar rats.


METHODS
Animals underwent a basilar cistern inoculation of group B Streptococci to induce meningitis. Sixteen hours later animals were randomized to receive Bocaspartyl (OMe)-fluoromethyketone (BAF) for 4 days or placebo in addition to antibiotic therapy. The assessment of neurobehavioral performance was started 7 days after initiation of treatment and continued for the following 3 wks. A subgroup underwent early kill, at 5 days, to evaluate caspase 3 activity in brain tissue. There was a group of Sham instrumented animals.


RESULTS
BAF decreased caspase 3 activation in meningitic animals. There were no significant motor deficit differences between the infected groups. Cognitive performance was significantly improved in the BAF group.


CONCLUSIONS
These findings demonstrate that sustained systemic administration of BAF inhibits caspase 3 activation and decreases neurologic sequelae in a rat model of bacterial meningitis.
Irazuzta
Jose
J
University of Florida at Jacksonville, Wolfson's Children Hospital, Jacksonville, FL, USA. Irazuzta@aol.com
Pretzlaff
Robert K
RK
Zingarelli
Basilia
B
D000590:Amino Acid Chloromethyl Ketones / Q000627:therapeutic use*; D000818:Animals; D001927:Brain Diseases / Q000209:etiology* / Q000517:prevention & control*; D061945:Caspase Inhibitors; D008297:Male; D008586:Meningitis, Pneumococcal / Q000150:complications*; D051381:Rats; D017208:Rats, Wistar
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; C103192:butyloxycarbonyl-O-methyl-aspartyl-fluoromethyl ketone