Levels of matrix metalloproteinase-9 within cerebrospinal fluid in a rabbit model of coccidioidal meningitis and vasculitis.
Matrix metalloproteinase (MMP)-9 is produced by the central nervous system and inflammatory cells in a variety of inflammatory conditions in both animals and humans. MMP-9 promotes inflammation, breakdown of the blood-brain barrier, and vasculitis. Because vasculitis is seen frequently in patients with coccidioidal meningitis (CM), this study evaluated the presence of MMP-9 within the cerebrospinal fluid (CSF) of rabbits infected intracisternally with Coccidioides immitis arthroconidia. Infected rabbits demonstrated systemic and neurological sequelae to infection, including CSF pleocytosis. Levels of MMP-9 within CSF were assayed by use of zymography and compared with MMP-2 levels, which served as an internal control. Elevated levels of MMP-9 were detectable by day 3, continued to increase through day 10, and declined by day 15 after infection. MMP-9 may contribute to inflammation and vasculitis in this animal model. Future work can focus on evaluation of MMP inhibitors, to gain a better perspective of the role of this MMP in CM.
Williams
Paul L
PL
Kaweah Delta Health Care District, Visalia. Pwilliam@pol.net
Leib
Stephen L
SL
Kamberi
Perparim
P
Leppert
David
D
Sobel
Raymond A
RA
Bifrare
Yoeng-Delphine
YD
Clemons
Karl V
KV
Stevens
David A
DA
D000818:Animals; D003045:Coccidioides / Q000472:pathogenicity*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid*; D016921:Meningitis, Fungal / Q000382:microbiology / Q000503:physiopathology*; D011817:Rabbits; D020293:Vasculitis, Central Nervous System / Q000382:microbiology / Q000503:physiopathology*
D020780:Matrix Metalloproteinase 9