| Experimental autoimmune encephalomyelitis is a myelin antigen-driven, T cell-mediated CNS autoimmune disease, which is characterized by perivascular inflammatory infiltration, BBB breakdown and white matter demyelination. The disease shows an acute clinical phase followed by recovery and is an animal model of MS which mechanism is unknown. The present study is designed to investigate the kinetic changes and correlation of BBB function and ICAM-1 expression during EAE in Wistar rats. The EAE rats were induced by injecting subcutaneously an emulsion of GPSCH and CFA. In addition, each rat received an intracutaneous injection of pertussis. Albumin in serum and CSF samples was examined on the days of 4,6,8,10,12,14,16,18 and 20 p.i.. The integrity of BBB was assessed by caculating CSF to serum albumin quotient (QA). At the same time the brains, spinal cords, thymus and inguinal lymph nodes were removed for paraffin sections cutting. These sections were used for HE staining and ICAM-1 semiquantitative immunohistochemical staining. The results showed as follows:1. None of EAE rats on days 4,6 and 8 p.i. showed clinical signs whichbecame apparent on day 10 p.i. (2.33±0.76; n=6). On days 12 and 14 p.i. the symptoms reached the peak (3.75±0.54; n=12). EAE rats showed loss of weight, hindlimb paralysis with incontinence, ataxia and even dying state. On day 16 p.i. most of animals began to remit (2.08±0.66; n=6) until all the symptoms disappeared on day 20 p.i.. Clinical scores exhibited time p.i.- dependent dynamic changes which corresponded with pathological findings.2. On day 6 p.i. QA of EAE rats had a slight increase which showed little significant difference from one of controls. While from day 8 to 20 p.i. there was a significant increase of QA. The increase of QA on day 8 p.i. was prior to development of clinical symptoms. QA of EAE rats showed dynamic changes with days p.i. The enhancement of QA on days 10, 12 and 14 p.i. was significant as compared to ones on days 6,8,18 and 20 p.i.. The peak of QA was on day 12 p.i. (8.82±2.41), but it was a little significant increase in comparision to QA on day 14 p.i. (q=0.68; p=0.46). There was no significant difference of QA among on days 8,18 and 20 p.i.3. The results of ICAM-1 semiquantitative IHC showed that on days 4,6 and 20 p.i. there was similar ICMA-1 staining between EAE rats and controls, but from day 8 to 18 p.i. the expression of ICAM-1 in EAE rats had a significant enhancement as compared to that in controls. The expression of ICAM-1 on day 8 p.i. was prior to onset of clinical symptoms. There was a significant increase of expression on days 10,12,14,16 p.i. as compared to that on days 8,18 p.i. and the peak of thatwas on day 12 p.i. But there was little significant difference among on days 10,12 and 14 p.i. The positive expression on day 16 p.i. showed significant reduction in comparision to that on day 12 p.i. while there was no significant difference among on days 16,10 and 14 p.i.. 4. The results in EAE rats from day 10 to 16 p.i. (n=24) showed positive correlation among clinical scores, QA and ICAM-1 semiquantitativeexpression, respectively. Conclusion1. During EAE both BBB damage and expression of ICAM-1 in CNS were prior to development of clinical signs and showed dynamic changes along with days p.i..2. During EAE BBB destruction involved many factors and up-regulation expression of ICAM-1 may play an important role. |
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