Glucosamine reduces blood-brain barrier disruption by inhibiting the expression of matrix metalloproteinase-9 in experimental autoimmune encephalomyelitis rats

doi:10.5246/jcps.2011.02.024

Abstract

Abstract: We investigated the effects of glucosamine (GS) on blood-brain barrier (BBB) function and matrix metalloproteinase-9 (MMP-9) expression in rats with experimental autoimmune encephalomyelitis (EAE). Animals were randomly divided into three groups, among which the EAE and GS groups were immunized with complete antigen and pertussis toxin, and the adjuvant group was immunized with complete Freund’s adjuvant and pertussis toxin. Rats were treated by peritoneal injection of GS 180 mg/(kg·d) in the GS group and peritoneal injection of phosphate-buffered saline 4.5 mL/(kg·d) in the EAE and adjuvant groups. We proposed to assess the integrity of BBB by calculating cerebrospinal fluid to serum albumin quotient (QA) on days 6, 8, 10, 12, 14, 16 and 18 post-immunization. At the same time, the brains and spinal cords were removed for MMP-9 immunohistochemical staining. Experiments demonstrated that in the EAE group, QA value and MMP-9 expression were highly elevated and up-regulated and correlated to disease severity. Moreover, there was statistically significantly positive correlation between QA value and MMP-9 expression. In the GS group, we observed that the mean disease onset date was delayed, the incidence and mean score of symptom were suppressed at the peak phase of disease (P<0.05). Furthermore, QA value and MMP-9 expression in the GS group showed stronger inhibition when compared with those of the EAE group (P<0.05). Our study showed that GS would reduce the BBB breakdown and leukocyte trafficking by inhibiting the production of MMP-9 and mitigate EAE.

Key words: Glucosamine, Experimental autoimmune encephalomyelitis, Blood-brain barrier, Matrix metalloproteinase-9

CLC Number:

R964

Supporting:

Chun-Yun Liu, Ling Feng, Jie-Zhong Yu, Min-Fang Guo, Yong-Sheng Sun, Ning Ji, Jian Meng, Li-Yun Liang, Cun-Gen Ma^*. Glucosamine reduces blood-brain barrier disruption by inhibiting the expression of matrix metalloproteinase-9 in experimental autoimmune encephalomyelitis rats [J]. , DOI: 10.5246/jcps.2011.02.024.

References

[1] Guo, M.F.; Ji, N.; Ma, C.G. Neurosci. Bull. 2008, 24, 381-386.
[2] Buhler, L.A.; Samara, R.; Guzman, E.; Wilson, C.L.; Krizanac-Benqez, L.; Janiqro, D.; Ethell D.W. BMC. Neurosci. 2009, 10, 17.
[3] Kurzepa, J.; Bartosik-Psujek, H.; Suchozebrska-Jesionek, D.; Rejdak, K.; Stryjecka-Zimmer, M.; Stelmasiak, Z. Neurol. Neurochir. Pol. 2005, 39, 63-67.
[4] Ma, L.; Rudert, W.A.; Harnaha, J.; Wright, M.; Machen, J.; Lakomy, R.; Qian, S.; Lu, L.; Robbins, P.D.; Trucco, M.; Giannoukakis, N. J. Biol. Chem. 2002, 277, 39343-39349.
[5] Zhang, G.X.; Yu, S.; Gran, B.; Rostami, A. J. Immunol. 2005, 175, 7202-7208.
[6] Reginster, J.Y.; Deroisy, R.; Rovati, L.C.; Lee, R.L.; Lejeune, E.; Bruyere, O.; Giacovelli, G.; Henrotin, Y.; Dacre, J.E.; Gossett, C. Lancet. 2001, 357, 251-256.
[7] Toft-Hansen, H.; Nuttall, R.K.; Edwards, D.R.; Owens, T. J. Immunol. 2004, 173, 5209-5218.
[8] Pachter, J.S.; de Vries, H.E.; Fabry, Z. J. Neuropathol. Exp. Neurol. 2003, 62, 593-604.
[9] Nessler, S.; Boretius, S.; Stadelmann, C.; Bittner, A.; Merkler, D.; Hartung, H.P.; Michaelis, T.; Brück, W.; Frahm, J.; Sommer, N.; Hemmer, B. Brain. 2007, 130, 2186-2198.
[10] Dong, M.; Liu, R.C.; Guo, L.; Li, C.Y. Chin. J. Immunol. 2006, 22, 870-875.
[11] Ma, C.G.; Yu, J.Z.; Ji, N. J. Neuroimmunol. 2008, 203, 145-146.
[12] Engelhardt, B.; Wolburg-Buchholz, K.; Wolburg, H. Microsc. Res. Tech. 2001, 52, 112-129.
[13] Yu, J.Z.; Ji, N.; Sun, Y.S.; Liu, Y.; Liang L.Y.; Ma, C.G. Chin. J. Neuroimmunol. Neurol. 2009, 16, 109-113.
[14] Ma, C.G.; Fan, H.C.; Yu, J.Z.; Guo, M.F.; Ren, X.R.; Ji, N.; Feng, L.; Liang, L.Y.; Xiao, B.G. J. Neurol. Sci. 2009, 285, S200-S201.
[15] Weaver, A.; Goncalves da Silva., A.; Nuttall, R.K.; Edwards, D.R.; Shapiro, S.D.; Rivest, S.; Yong, V.W. FASEB J. 2005, 19, 1668-1670.
[16] Rosenberg, G.A.; Dencoff, J.E.; Correa, N. Jr.; Reiners, M.; Ford, C.C. Neurology. 1996, 46, 1626-1632.
[17] Stamenkovic, I. J. Pathol. 2003, 200, 448-464.
[18] Fitzgerald, D.C.; Ciric, B.; Touil, T.; Harle, H.; Grammatikopolou, J.; Das, Sarma. J.; Gran, B.; Zhang, G.X.; Rostami, A. J. Immunol. 2007, 179, 3268-3275.