Table 2.

Future research strategies for experimental multiple sclerosis research

MS-related topic	MS pathology	Suggested strategy
Role of CD8+ T-cells	Major contribution of CD8+ T-cells in the inflammatory process of MS [24, 53, 62]	(1) Expand knowledge on mechanisms of inflammation and tissue injury in existing models of CD8+ T-cell-mediated brain inflammation (2) Define mechanisms, how CD8+ T-cell autoimmunity can be induced by active sensitization
Role of B-cells	Therapeutic effect of B-cell depleting therapies [61, 150, 152]	Create new in vivo models to test the role of B-cells in neuroinflammation
Mechanisms of Demyelination	Presence of a soluble demyelinating (cytotoxic) factor in serum and cerebrospinal fluid of MS patients [98]	(1) Define the nature of the demyelinating factor in serum and CSF of MS patients beyond anti-MOG antibodies (2) Define its role in different models of brain inflammation in vivo
Models for progressive MS	MS lesions develop on the background of pro-inflammatory microglia activation seen already in the normal white matter of age matched controls [53, 144]	(1) Test the effect of different microglia pre-activation in different models of brain inflammation (a) non-SPF environment (b) systemic innate immunity activation prior to induction of autoimmune inflammation (c) genetic models of microglia pre-activation
	Mitochondrial damage and “virtual” hypoxia play an important role in demyelination and neurodegeneration in MS, being most pronounced in the progressive stage [103, 104]	(1) Define mechanisms of tissue injury in mitochondrial mutants (2) Combine models of mitochondrial dysfunction with models of brain inflammation