[Abstract Title]. - Society for Neuroscience

Abstract: Multiple sclerosis (MS) is an inflammatory and demyelinating CNS disease that
affects ~400,000 adults in the US; however, currently available treatments remain unsatisfactory.
Clinical MRI is routinely utilized for diagnosis and prognosis of MS and as a primary outcome
measure in clinical trials. Preclinically, experimental autoimmune encephalomyelitis (EAE) is
characterized by many of the same pathophysiological processes observed in MS and is therefore
commonly employed for development of new therapeutics for MS. Recently, ultrasmall
superparamagnetic iron oxide (USPIO)-enhanced T2-weighted MRI was described as an
invaluable tool that allows in vivo monitoring of infiltrating macrophages, the predominant
effector cells in EAE, allowing visualization of new lesions during disease development. Here,
we describe how we have developed imaging methods to visualize these inflammatory responses
(macrophage infiltration and blood-brain barrier breakdown) using molecular MRI in EAE rats
immunized with myelin oligodendrocyte glycoprotein (MOG). With a goal to characterize the
CNS lesions and elucidate the implications on observed neurological deficits, behavioral
symptoms were scored daily, and rats were imaged longitudinally during acute, remission, and
relapse phases using a 7T MRI scanner. We demonstrated a distinct spatiotemporal pattern of
CNS lesions that unveils the involvement of spino-olivocerebellar pathways. In particular,
lesions of the inferior olives were observed primarily in the acute phase whereas lesions of
cerebellum and spinal cord were observed during the relapse phase and appeared to correlate
with severity. Histological and immunochemical studies in the same animal confirm the presence
of USPIO uptake as well as activated macrophages in demyelinated lesion areas. Further, clinical
scores recorded from these animals revealed observations of loss of tail tone, abnormal gait, and
paralysis that agree with the functional role of spino-olivocerebellar pathways in coordination
and movement. Collectively, our results provide a new perspective for further understanding the
underlying pathology of this MS model.
Disclosures: M.V. Pai, None; P.F. Bousquet, None; A. Schwartz, None; B.L. Mcrae,
None; E.M. O'Connor, None; C.M. Nelson, None; V.P. Hradil, None; B.F. Cox, None; G.B.
Fox, None; C. Chin, None.
Poster
251. Demyelinating Disorders: Animal Models and Human Studies I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 251.21/W14
Topic: C.08.b. Animal models
Support: NINDS, 5R01NS056427
Sanitätsrat Dr. Emil Alexander Huebner & Gemahlin Foundation, Germany