Intraspinal administration of an antibody against CD81 enhances functional recovery and tissue sparing after experimental spinal cord injury
- 作者：S. Dijkstra ; S. Duis ; I.M. Pans ; A.J. Lankhorst ; F.P.T. Hamers ; H. Veldman ; P.R. Bä ; r ; W.H. Gispen ; E.A.J.Joosten and E.E. Geisert ; Jr.
- 关键词：Drug delivery ; Tetraspanins ; Therapeutic antibodies ; Spinal cord injury ; Inflammation ; Gliosis ; Neuroprotection
- 刊名：Experimental Neurology
- 出版年：2006
- 期刊代码：78_00144886
- 类别：neu
- 出版时间：November 2006
- 卷：200
- 期：2
- 页码：57-66
- 文件大小：500 K
摘要
We previously demonstrated that the tetraspanin protein CD81 is up-regulated by astrocytes and microglia after traumatic spinal cord injury in rats and that CD81 is involved in adhesion and proliferation of cultured astrocytes and microglia. Since these reactive glial cells contribute to secondary damage and glial scar formation, we studied the effect of local administration of an anti-CD81 antibody in experimental spinal cord injury. Adult rats were subjected to a moderate spinal cord contusion injury and treated for 2 weeks with different doses of the anti-CD81 antibody AMP1 (0.5–5 μg/h) or non-immune IgG (5.0 μg/h). A technique was developed to infuse the antibodies directly into the lesion site via an intraspinal cannula connected to a pump. Functional recovery was monitored during 8 postoperative weeks by means of the Basso, Beattie and Bresnahan (BBB) locomotor rating scale, the BBB subscore and Grid-walk test. At the end of the study, quantitative histology was performed to assess tissue sparing. Our data showed that by itself cannulation of the lesion site resulted in minimal functional and histological impairments. Application of 0.5 μg/h AMP1 resulted in a marked functional recovery (BBB 2 points; Grid-walk 30%less errors compared to control). This recovery was accompanied by an 18%increase in tissue sparing at the lesion epicentre. No gross histological changes in glial scarring were apparent. Our data demonstrate beneficial effects of an anti-CD81 antibody on functional recovery in spinal cord injured rats and suggest that this effect is mediated through a reduction in secondary tissue loss.