Table 1 Potential treatments targeting peripheral immune responses for central nervous system injuries
Drug | Drug target/type | Disease | Effector cell | Primary role | references |
|---|---|---|---|---|---|
Fingolimod | Sphingosine 1-phosphate receptor | Ischemic Stroke | Microglia | Regulation of microglia M2 polarization Neuroprotective function Reduces volume of brain tissue damage | Proc Natl Acad Sci USA. 2014 Dec 23;111(51):18315-20. Circulation. 2015 Sep 22;132(12):1104-1112. |
SAH | Neutrophil | Significantly reduced intravascular leukocyte adhesion Improved neurologic prognosis after SAH in rats | J Neuroinflammation. 2015 Jan 27:12:16. | ||
ICH | T-cell NK cell | Blocking T or NK cell infiltration into the CNS Improves neurologic prognosis after SAH in rats | Neurosci Bull. 2015 Dec;31(6):755 − 62. | ||
Minocycline | Antibiotics | Ischemic Stroke | Microglia | Resulted in a significant reduction in the patient’s MRS score | Neurology. 2007 Oct 2;69(14):1404-10. Stroke. 2010 Oct;41(10):2283-7. |
TBI | Inhibits microglia polarization to M1 type and promotes mechanization to M2 type Reduces the size of the injury site | J Neurotrauma. 2010 May;27(5):911 − 21. | |||
ICH | Microglia/macrophage | Decreased number of microglia and macrophages around the hematoma Decreased brain water content Reduced levels of TNF-α and MMP12 | Acta Neurochir Suppl. 2010:106:147 − 50. Exp Neurol. 2007 Oct;207(2):227 − 37. | ||
BI1002494 | Splenic tyrosine kinase(SYK) inhibitor | Ischemic Stroke | Platelet | Inhibits thrombosis and reduces damage | Arterioscler Thromb Vasc Biol. 2016 Jun;36(6):1247-53. |
Recombinant T-cell receptor ligand(RTL) | Recombinant T-cell receptor | T-cell | Reduced infarct size by 50% Reduced the number of immune cells recruited in the brain | Transl Stroke Res. 2016 Feb;7(1):70 − 8. Neuroscience. 2015 Mar 12:288:112-9. | |
Bexarotene | Retinoid X receptor(RXR) | N2 neutrophil | Increases the number of N2 neutrophils Neuroprotective effect | Pharmacol Res. 2015 Dec:102:298–307. | |
Bone marrow mononuclear cell(BMMCs) | / | Monocyte | Improved clinical functional prognosis | Cell Transplant. 2014:23 Suppl 1:S57-64. Stroke. 2016 Jul;47(7):1817-24. | |
Granulocyte colony-stimulating factor(G-CSF) | Granulocyte colony-stimulating factor receptor(G-CSFR) | Monocyte Microglia | Promotes microglia polarization to M2 type Promotes axonal germination | Stroke. 2012 Feb;43(2):405 − 11. Exp Neurol. 2015 Jan:263:17–27. | |
Recombinant human IL-1 receptor antagonists | IL-1 receptor | Multi-cell type | NIH Stroke Scale Scores and Modified Rankin Scale (mRS) Scores Increased | J Neurol Neurosurg Psychiatry. 2005 Oct;76(10):1366-72. | |
Natalizumab | α4-integrin | T-cell | Reduction of cerebral infarct volume | Brain. 2011 Mar;134(Pt 3):704 − 20. Stroke. 2014 Jun;45(6):1610-1. | |
Dexamethasone/hydrocortisone | Ras homolog family member (Rho)-A and-B proteins | TBI | Multi-cell type | Reduces the intensity of the immune response Reduces the number of circulating lymphocytes | J Neurotrauma. 2014 Apr 15;31(8):699–712. J Neuroinflammation. 2016 Aug 25;13(1):197. |
Atorvastatin | HMG-CoA reductase | T-reg cell Microglia Macrophage | Neuroprotective effects Increases the number of Tregs Increases expression of IL-10 | Neurocrit Care. 2017 Feb;26(1):122–132. J Neurotrauma. 2016 Aug 15;33(16):1492 − 500. J Neuroinflammation. 2017 Aug 23;14(1):167. | |
Anti-HMGB1 monoclonal antibody | HMGB1 | Endothelial cell Microglia | Reducing disruption of the blood-brain barrier Reduces cerebral edema Limit inflammatory cascade | Ann Neurol. 2012 Sep;72(3):373 − 84. Stroke. 2011 May;42(5):1420-8. | |
Methylene blue | GABAA | Microglia | Improves blood-brain barrier integrity Reduces volume of damage Protects against neuronal death | Front Neurol. 2019 Nov 8:10:1133. Neuropharmacology. 2017 Jun:119:100–110. | |
Metformin | ERK1/2 p38-MAPK | Microglia Neutrophil Monocyte | Reduced microglia activation Decreased neutrophil/lymphocyte ratio | J Neurol. 2019 Aug;266(8):1988–1997. Brain Res Bull. 2018 Jun:140:154–161. | |
T-0080 | Formyl peptide receptor 1(FPR1) | ICH | Microglia Neutrophil | Attenuates activation of neutrophils by microglia May reduce cerebral edema Improves neurologic prognosis after ich | Curr Neuropharmacol. 2021;19(9):1590–1605. |
Rapamycin | mTOR | T-reg cell | Increase Tregs cells in brain tissue Improves neurological function after ICH | J Cereb Blood Flow Metab. 2017 Mar;37(3):967–979. J Neuroinflammation. 2014 Mar 6:11:44. | |
Celecoxib | Cyclooxygenase2 | Multi-cell type | Reduction of inflammatory cell infiltration, cerebral edema and subsequent perihematoma cell death | J Cereb Blood Flow Metab. 2004 Aug;24(8):926 − 33. Eur J Neurol. 2013 Aug;20(8):1161-9. | |
Rosiglitazone | PPAR-γ/CD36 | Microglia/macrophage | Facilitate hematoma clearance after ICH | J Neuropathol Exp Neurol. 2000 Aug;59(8):641 − 51. Int J Stroke. 2013 Jul;8(5):388 − 96. | |
IL-2 | IL-2 receptor | SAH | Neutrophil | Suppression of brain pro-inflammatory factors and peripheral neutrophils Reduces neuronal damage | ACS Chem Neurosci. 2021 Feb 3;12(3):430–440. |