Intracerebral injection of myelin basic protein (MBP) induces inflammation in brain and causes paraplegia in MBP-sensitized B6 mice

Abstract

SUMMARY Brain inflammation and paraplegia can be induced by an additional intraperitoneal (i.p.) and intracerebral (i.c.) restimulation in B6 mice after standard immunization with MBP in Freund's complete adjuvant (FCA) and Bordetella pertussis coadjuvant. Only the combination of i.p. MBP/FCA and i.c. MBP injection could induce clinical paraplegia; either one alone was not effective. Clinical symptoms would develop 2 days after the i.c. injection. The induction of paraplegia was MBP-specific, as irrelevant bovine serum albumin with the same protocol could not induce it. The i.p. restimulation was requisite and needed the MBP in FCA, as MBP in PBS was ineffective. Histopathological observation manifested cellular infiltration by leucocytes in perivascular spaces and cerebral cortex. Neutrophils were prominent at 12 h after i.c. injection, then were replaced by mononuclear cells 24 h later. There were dynamic changes in cell number and immunophenotype of VLA-4+ expression in cervical lymph node cells after i.c. injection. The cells derived from cervical lymph nodes had higher MBP-stimulated proliferation than that of distal lymph nodes. This additional i.p. and i.c. stimulation provides a new manipulation to study brain inflammation.