The bands observed in the CSF of the MI-503 in vitro control dogs had a homogeneous intensity, whereas the bands observed in the CSF

of the infected animals presented remarkable variation. We detected the latent form of MMP-2 (72 kDa) in all dogs of both groups. However, only 24·0% (12/50) of the infected dogs and 60·0% (6/10) of the uninfected ones presented bands indicative of active MMP-2 (66 kDa). The level of the latent MMP-2 was significantly different between the infected and uninfected dogs (P = 0·0041) and no difference regarding the active MMP-2 was noticed (P = 0·3285). In contrast, both the latent (92 kDa) and the active (86 kDa) forms of MMP-9 were detected in some infected dogs, and no activity was observed in the RXDX-106 control group

(P = 0·0005 and P = 0·0003, respectively). The latent form of MMP-9 was detected in 34·0% (17/50), whereas the active MMP-9 was found in 32·0% (16/50) of the infected dogs (Figure 2). Although MMP-9 has not been detected in all the infected dogs, in the animals which this enzyme was present, there was observed a moderate positive correlation (P < 0·0001) between the latent and active forms (Figure 3). Regarding MMP-2, no correlation was noticed. From the 50 infected dogs, 17 animals were classified as asymptomatic; 12 were classified as oligosymptomatic (one or more mild and/or localized symptom) and 21 dogs were designed as symptomatic (one or more severe and/or diffuse symptom). those When these three subgroups were compared, there was still no difference among them regarding any forms of MMPs (Figure 4). In this study, the latent and active forms of MMP-9 were detected in the CSF of some dogs with VL, but not in the CSF of uninfected dogs, and, surprisingly, in the infected dogs, it was noted a decrease in both active and latent forms of MMP-2 in comparison with the control dogs. It has been previously reported that the latent and active forms of MMP-9 are present in the CSF and brain of dogs only during inflammation (13–15). In a study using

dogs with acute spinal cord injury because of intervertebral disc disease, MMP-2 was detected in all the animals and frequently detected MMP-9 in dogs with paraplegia (14). Paraparesis and paraplegia are also the most common neurological alterations in dogs with VL (2). Therefore, VL should be included in the differential diagnosis for all patients presented with neurological involvement, including infectious, neoplastic and traumatic diseases. During bacterial meningitis, MMP-9 mRNA within the CSF was elevated in 10–100 times, while MMP-2 mRNA was kept in basal levels (16). Additionally, it was noticed a positive correlation between the latent and active forms of MMP-9, and, even if this correlation was moderate, it is indicative of MMP-9 activation within the CSF.