Nathan Kung, Serena Shimshak, Jamie Wong, and Saud A. Sadiq, MD Presented at the American Academy of Neurology (AAN) 2018 Annual Meeting, held April 21-27, 2018 in Los Angeles, CA.
Objective: To investigate whether primary progressive MS (PPMS) cerebrospinal fluid (CSF) impacts
remyelination after lysolecithin-induced demyelination.
Background: In PPMS the clinical course is progressive from disease onset suggesting that remyelination is
impaired in contrast to relapsing-remitting (RRMS) forms of the disease. To investigate this phenomenon we
used the lysolecithin-induced demyelination model of the disease. In this model, remyelination spontaneously
commences usually 7 days post lysolecithin administration. We studied whether factors present in CSF from
PPMS patients would inhibit this remyelination.
Mice underwent a laminectomy at cervical level 5 (C5) and 1μl of 1% lysolecithin was injected into the dorsal
column. At 5 days post lysolecithin injection, 3μl cerebrospinal fluid from untreated PPMS patients was
injected into the subarachnoid space also at C5. Control mice were injected with saline or CSF obtained from
healthy individuals. Behavioral deficits were assessed at multiple time points post CSF administration. Mice were
perfused 12 days after lysolecithin injection and pathology was assessed in the spinal cord.
PPMS CSF-injected mice exhibited significantly impaired forelimb function and increased tail flaccidity compared
to controls. Luxol fast blue staining revealed a significantly larger volume of demyelination in PPMS CSF-injected
mice than mice injected with saline or healthy control CSF. Mice injected with PPMS CSF also showed a
significant increase in microglial activation and an increase in reactive astrogliosis, as assessed by Iba-1 and
GFAP immunostaining respectively. No significant change in the number of proliferating oligodendrocyte
progenitor cells, as assessed by NG2 and Ki67, or mature oligodendrocytes, assessed by APC and Olig2, was
Conclusions: Intrathecal delivery of PPMS CSF at the site of a lysolecithin-induced lesion yielded larger lesions,
accompanied by increased microglial activation and reactive astrogliosis in the cervical spinal cord, as compared
to controls. Identification of the CSF factors responsible for this delay in remyelination is an important next step.
Study Supported by: Tisch MS Research Center of New York (private funds)