Pneumococcal meningitis is a relevant clinical disease characterized by an intense inflammatory reaction into the subarachnoid and ventricular spaces, leading to blood-brain barrier breakdown,
hearing loss, and
cognitive impairment.
Matrix metalloproteinases (
MMPs) are capable of degrading components of the basal
laminin, thus contributing to BBB damage and neuronal injury. In the present study, we evaluated the effects of MMP-2, MMP-9, and
MMP-2/9 inhibitors on BBB integrity, learning, and memory in Wistar rats subjected to
pneumococcal meningitis. The animals underwent a magna cistern tap and received either 10 µL sterile saline as a placebo or an equivalent volume of a Streptococcus pneumoniae
suspension at a concentration of 5 × 10(9)cfu/mL. The rats were randomized into different groups that received adjuvant treatment with MMP-2, MMP-9 or
MMP-2/9 inhibitors. The BBB integrity was evaluated, and the animals were habituated to open-field and object recognition tasks 10 days after
meningitis induction. Adjuvant treatments with inhibitors of MMP-2 or
MMP-2/9 prevented BBB breakdown in the hippocampus, and treatments with inhibitors of MMP-2, MMP-9 or
MMP-2/9 prevented BBB breakdown in the cortex. Ten days after
meningitis induction, the animals that received adjuvant treatment with the inhibitor of
MMP-2/9 demonstrated that animals habituated to the open-field task faster and enhanced memory during short-term and long-term retention test sessions in the object recognition task. Further investigation is necessary to provide support for
MMP inhibitors as an alternative treatment for
bacterial meningitis; however, these findings suggest that the
meningitis model could be a good research tool for studying the biological mechanisms involved in the behavioral alterations associated with
pneumococcal meningitis.