Table 1.
Disease-modifying effects of pharmacological agents in EAE, CPZ and TMEV animal models of MS
| Effect of pharmacological agent | Pharmacological agent |
|---|---|
| EAE mouse studies | |
| Improved behavioral performance | CTK 01512-2, glatiramer acetate |
| Alleviated demyelination of spinal cord | Cerebrolysin, CTK 01512-2, C-phycocyanin, lanthionine ketamine ester, adrenomedullin |
| Alleviated demyelination of optic nerve | ST266, lanthionine ketamine ester |
| Protected against demyelination of cerebral cortex | caffeine |
| Decreased the number of microglia in medulla | Cerebrolysin |
| Decreased inflammation in the brain and spinal cord by altering the balance of proinflammatory/anti-inflammatory cytokines | CTK 01512-2, C-phycocyanin, caffeine, adrenomedullin |
| Decreased astrocyte activation in the spinal cord and microglia activation in the brain | CTK 01512-2 |
| Decreased astrocyte activation and microglia/macrophage activation in the striatum | Siponimod |
| Decreased activated microglia/macrophages in the spinal cord | C-phycocyanin |
| Decreased the number of macrophages in CNS infiltrates | Adrenomedullin |
| Decreased infiltration of inflammatory cells into the spinal cord and optic nerve | Melatonin, ST266, trichostatin A, caffeine, adrenomedullin, glatiramer acetate |
| Decreased the numbers of infiltrating CD4 T cells into the brain, particularly of IFN-γ- and IL- 17-producing Th1 and Th17 cells | Adrenomedullin |
| Increased the percentage of IL-10-secreting CD4+CD25+FoxP3+ Treg cells in the CNS | Adrenomedullin |
| Decreased the levels of oxidative stress in the brain and spinal cord | Melatonin, white grape juice extract |
| Decreased the levels of ROS in optic nerve during optic neuritis | ST266 |
| Decreased parameters of oxidative stress in blood lysates | C-phycocyanin |
| Decreased the number of injured axons in the spinal cord | Diarylpropionitrile |
| Decreased proinflammatory phenotype of myeloid cells in the CNS | Diarylpropionitrile |
| Increased the percentages of mature and immature oligodendrocytes in dorsal white matter of spinal cord | Diarylpropionitrile |
| Decreased T-lymphocytes in the blood | Siponimod |
| Decreased the number of infiltrating lymphocytes in the striatum | Siponimod |
| Rescued GABAergic interneuron loss in the striatum | Siponimod |
| Decreased infiltration of T lymphocytes, monocytes and neutrophils in the white matter of the spinal cord | White grape juice extract |
| Decreased TNF-α in the spinal cord | White grape juice extract |
| Decreased the number of apoptotic cells in the spinal cord | White grape juice extract |
| Decreased neurodegeneration in the optic nerve | Lanthionine ketamine ester |
| Decreased the percentage of axons with abnormal mitochondria and loss of contact in the optic nerve | Lanthionine ketamine ester |
| Decreased the number of axons with condensation in the spinal cord | Lanthionine ketamine ester |
| Decreased the ratio between MOG-specific IgG2a and IgG1 antibodies | Adrenomedullin |
| Increased the gene expression of neuroprotective factors BDNF and ADNP in the spinal cord | Adrenomedullin |
| Increased MBP staining intensity in spinal cord dorsal column | Glatiramer acetate |
| Reversed a decrease in oligodendrocyte lineage cells in the spinal cord dorsal column | Glatiramer acetate |
| Decreased axonal loss and the number of damaged axons in the spinal cord ventral column | Glatiramer acetate |
| Decreased inflammatory lesions in the corpus callosum | Glatiramer acetate |
| Decreased CD45+ activated microglia and CD3+ T cell infiltrates in the corpus callosum | Glatiramer acetate |
| EAE rat studies | |
| Decreased demyelination of the optic nerve | Memantine hydrochloride |
| Decreased inflammatory cell infiltration in the brain, brainstem, and spinal cord | Pien Tze Huang |
| Decreased inflammatory cell infiltration in the optic nerve | Memantine hydrochloride |
| Decreased axonal loss in the optic nerve | Memantine hydrochloride |
| Decreased proinflammatory cytokines and chemokines in the spinal cord | Pien Tze Huang, dihydrotestosterone |
| Increased the Olig2 and MBP levels in the brain | Pien Tze Huang |
| Decreased astrocytes in the spinal cord | Dihydrotestosterone |
| Decreased microglia/macrophages and their reactive phenotype in the white matter of the spinal cord | Dihydrotestosterone |
| Decreased reactivity of microglia at lamina IX of ventral horn of the spinal cord in exacerbation phase of EAE | Pregabalin |
| Decreased astrocyte reactivity at lamina IX of ventral horn of the spinal cord in the exacerbation phase during peak disease | Pregabalin |
| Decreased oxidative stress in the spinal cord | Dihydrotestosterone |
| Reversed the decrease in mtDNA levels in the spinal cord | Dihydrotestosterone |
| Effect of pharmacological agent | Pharmacological agent |
| CPZ mouse studies | |
| Improved behavioral performance | Bilobalide, linagliptin |
| Increased myelin in the corpus callosum | Bilobalide, linagliptin |
| Increased MBP and mature oligodendrocytes in the brain | Bilobalide |
| Decreased MOG35-55 specific antibody in serum and the brain | Bilobalide |
| Decreased infiltration of CD4+ T cells, CD68+ macrophages and B220+ B cells into the brain | Bilobalide |
| Decreased the number of microglia in the brain | Bilobalide, BLZ945 |
| Inhibited the activation of microglia or M1 polarization of microglia in the brain | Bilobalide |
| Decreased the levels of the proinflammatory cytokines IL-1β, IL-6 and TNF-α in the brain | Bilobalide, linagliptin |
| Decreased the migration and accumulation of microglia toward the myelin sheath in the corpus callosum, striatum and medial septal nucleus | Bilobalide |
| Decreased oxidative stress in the brain | Linagliptin |
| Increased MBP-positive remyelination and mature oligodendrocytes in cortex/striatum | BLZ945 |
| Increased the numbers of mature oligodendrocytes, accelerated remyelination, and increased the numbers of myelinated axons | Indomethacin |
| TMEV study | |
| Improved nocturnal motor activity | rHIgM12 |
| Increased neuron cell bodies in the brainstem, and increased number of axons in the spinal cord | rHIgM12 |
ADNP: Activity-dependent neuroprotective protein; BDNF: brain-derived neurotrophic factor; CNS: central nervous system; CPZ: cuprizone; EAE: experimental autoimmune encephalomyelitis; GABA: gamma-aminobutyric acid; IFN-γ: interferon-γ; IL: interleukin; MBP: myelin basic protein; MOG: myelin oligodendrocyte glycoprotein; MS: multiple sclerosis; TMEV: Theiler’s murine encephalomyelitis virus; TNF-α: tumor necrosis factor-α.