Contributions
Abstract: EP1417
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Multiple sclerosis (MS) is thought to be an immune mediated disorder of the central nervous system that results in the damage of myelin as well as nerve fibers in the brain and in the spinal cord. Whereas currently available treatment options primarily modulate the immune system, the underlying neurodegeneration and demyelination is not addressed. Thus therapeutics promoting endogenous remyelination and reducing demyelination, as well as promoting neuroregeneration are highly promising for MS patients.
Currently available animal models for MS are limited by the fact of multifocal lesions and lack of clear separation of de and remyelination. This study aimed to generate two rat models of Lysophosphatidylcholine (LPC) induced focal de and remyelination in the spinal cord (SC) and corpus callosum (CC) in order to test the effect of remyelination therapies on myelin protection, remyelination and motor functional recovery. LPC could induce rapid demyelination and shows the spatial and temporal separation of demyelination and remyelination with minimal inflammation. This allows accurate quantitative biochemical readout of pharmacological agents on remyelination.
Adult male Sprague Dawley rats were subjected to unilateral stereotactic injection with 1% of LPC at Th8-9 for SC model and at CC for the CC model. As a control, rats were injected with 0.9% saline. Rats were perfused at days 3, 7, 15, 21, 28 and 42. Motor function tests like Open field test and horizontal ladder rung tests were done on weekly basis for the SC lesion model. Immunohistochemical analysis was done for inflammation, demyelination, neurofilament and NG2. Demyelination and inflammation were obvious from day 3 with the maximum extent by day 15 and remyelination was continued for 6 weeks after LPC injection.
Thus we describe robust pre-clinical models of demyelination and remyelination in the SC and CC. Using these models functional change can be objectively measureable by motor behavior (SC model) in correlation to histology improvement, as a proof concept of the study for screening candidate for remyelination promoting therapeutics.
Disclosure: All authors are employees of AbbVie. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication
Abstract: EP1417
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Multiple sclerosis (MS) is thought to be an immune mediated disorder of the central nervous system that results in the damage of myelin as well as nerve fibers in the brain and in the spinal cord. Whereas currently available treatment options primarily modulate the immune system, the underlying neurodegeneration and demyelination is not addressed. Thus therapeutics promoting endogenous remyelination and reducing demyelination, as well as promoting neuroregeneration are highly promising for MS patients.
Currently available animal models for MS are limited by the fact of multifocal lesions and lack of clear separation of de and remyelination. This study aimed to generate two rat models of Lysophosphatidylcholine (LPC) induced focal de and remyelination in the spinal cord (SC) and corpus callosum (CC) in order to test the effect of remyelination therapies on myelin protection, remyelination and motor functional recovery. LPC could induce rapid demyelination and shows the spatial and temporal separation of demyelination and remyelination with minimal inflammation. This allows accurate quantitative biochemical readout of pharmacological agents on remyelination.
Adult male Sprague Dawley rats were subjected to unilateral stereotactic injection with 1% of LPC at Th8-9 for SC model and at CC for the CC model. As a control, rats were injected with 0.9% saline. Rats were perfused at days 3, 7, 15, 21, 28 and 42. Motor function tests like Open field test and horizontal ladder rung tests were done on weekly basis for the SC lesion model. Immunohistochemical analysis was done for inflammation, demyelination, neurofilament and NG2. Demyelination and inflammation were obvious from day 3 with the maximum extent by day 15 and remyelination was continued for 6 weeks after LPC injection.
Thus we describe robust pre-clinical models of demyelination and remyelination in the SC and CC. Using these models functional change can be objectively measureable by motor behavior (SC model) in correlation to histology improvement, as a proof concept of the study for screening candidate for remyelination promoting therapeutics.
Disclosure: All authors are employees of AbbVie. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication