MATRIX METALLOPROTEINASES CONTRIBUTE TO THE BLOOD-BRAIN-BARRIER DISRUPTION DURING BACTERIAL-MENINGITIS

In this study, we investigated the involvement of matrix metalloprotei nases (MMPs) in the pathophysiology of bacterial meningitis. By using an enzyme immunoassay, high concentrations of MMP-3 mere detected in t he cerebrospinal fluid (CSF) of adult patients with bacterial meningit is but not in controls, and in patients with Guillain-Barre syndrome. Moreover, we observed significantly elevated concentrations of the tis sue inhibitor of metalloproteinase-1 (TIMP-1) in the CSF of patients w ith bacterial meningitis, compared with controls. In a rat model of me ningococcal meningitis, intracisternal injection of heat-killed mening ococci caused a disruption of the blood-brain barrier (BBB), an increa se in intracranial pressure, and CSF pleocytosis paralleled by the occ urrence of MMP-9 activity in the CSF 6 hours after meningococcal chall enge. The MMP inhibitor batimastat (BB-94) significantly reduced the B BB disruption and the increase in intracranial pressure irrespective o f the time of batimastat administration (15 minutes before and 3 hours after meningococcal challenge) but faded to significantly reduce CSF white blood cell counts. In conclusion, our results suggest that MMPs are involved in the alterations of BBB permeability during experimenta l meningococcal meningitis.