Distinct spatiotemporal pattern of CNS lesions revealed by USPIO-enhanced MRI in MOG-induced EAE rats implicates the involvement of spino-olivocerebellar pathways

Chin, Chih-Liang; Pai, Madhavi; Bousquet, Peter F.; Schwartz, Annette J.; O'Connor, Elizabeth M.; Nelson, Christine M.; Hradil, Vincent P.; Cox, Bryan F.; McRae, Bradford L.; Fox, Gerard B.

doi:10.1016/j.jneuroim.2009.03.012

« Previous Next »Journal of Neuroimmunology
Volume 211, Issue 1 , Pages 49-55, 25 June 2009

Distinct spatiotemporal pattern of CNS lesions revealed by USPIO-enhanced MRI in MOG-induced EAE rats implicates the involvement of spino-olivocerebellar pathways

Chih-Liang Chin
- Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
- Corresponding author. GPRD/Experimental Imaging, Dept. R4DF Bldg. AP9-1, 100 Abbott Park Road, Abbott Park, IL 60064-6119, USA. Tel.: +1 847 937 8093; fax: +1 847 935 9293.
Madhavi Pai
- Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
Peter F. Bousquet
- Department of Pharmacology, Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA
Annette J. Schwartz
- Department of Pathology, Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA
Elizabeth M. O'Connor
- Department of Pathology, Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA
Christine M. Nelson
- Department of Pharmacology, Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA
Vincent P. Hradil
- Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
Bryan F. Cox
- Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
Bradford L. McRae
- Department of Pharmacology, Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA
Gerard B. Fox
- Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA

Received 14 November 2008; received in revised form 16 February 2009; accepted 5 March 2009. published online 06 April 2009.

Abstract

USPIO-enhanced MRI allows non-invasive visualization of mononuclear cell infiltration into CNS lesions in MS and EAE. Herein, we show a distinct spatiotemporal pattern of CNS lesions that reveals the involvement of spino-olivocerebellar pathways in MOG-induced EAE rats using USPIO-enhanced MRI. Specifically, lesions of the inferior olives were observed primarily in the acute phase whereas lesions of cerebellum or spinal cord/brainstem were observed during the relapse phase. Further, behavioral deficits observed from these animals are consistent with the functional role of spino-olivocerebellar pathways in coordination and movement. Collectively, our results provide new insights into the pathophysiology of this animal model of MS.

Abbreviations: EAE, experimental autoimmune encephalomyelitis, MS, multiple sclerosis, CNS, central nervous system, MRI, magnetic resonance imaging, MRS, magnetic resonance spectroscopy, MR, magnetic resonance, MOG, myelin oligodentrocyte glycoprotein, MBP, myelin basic protein, BBB, blood–brain barrier, IFA, incomplete Freund's Adjuvant, DBA, diaminobenzidine, Gd-DTPA, gadolinium-diethyltriaminepenta acetic acid, USPIO, ultra-small superparamagnetic iron oxide, NBF, neutral buffered formalin, DA, dark agouti, BN, brown Norway