Hemophilus influenzae meningitis in the rat: Behavioral, electrophysiological, and biochemical consequences

Abstract

Hemophilus influenzae is the most common cause of bacterial meningitis in children, and a high percentage of survivors are at risk for long-term sequelae. To explore the mechanisms responsible for these sequelae, a neonatal rat model was used to define the behavioral, electrophysiological, and biochemical changes following meningitis. Three days after inoculation of 6-day-old rats with a minimum of 1 X 10(7) colony-forming units of a virulent Hemophilus influenzae, type b, cerebrospinal fluid and blood were cultured to confirm the presence of meningitis and bacteremia, respectively. At this time, forebrain norepinephrine and dopamine levels were significantly elevated in meningitic rats when standardized on a wet-weight basis. No changes in brain serotonin or heart norepinephrine levels could be found in the 9-day-old rats. No residual changes were found in steady-state concentrations of norepinephrine or dopamine in surviving adult rats. However, survivors that had had meningitis as neonates showed significant impairment in active and passive avoidance learning tasks and demonstrated a significantly higher level of activity during a habituation period in circular photocell activity cages. No change in the flinch-jump threshold was detected. Brainstem auditory evoked potentials showed delays of various waves in 3 of 10 Hemophilus influenzae type b-treated adult rats tested. These rats also exhibited markedly augmented locomotory responses to d-amphetamine (1 mg/kg), suggesting a long-lasting perturbation of central monoamine neuronal transmission.