Table 1.
Preclinical attempts to target neutrophils for treating AIS.
| Mechanism | Drug | Molecular targets | Outcomes | Reference |
|---|---|---|---|---|
| Infiltration inhibition | reparixin | CXCR1 CXCR2 | Reduced infarct volume; improved functional outcome | (205) |
| evasin-3 | CXCL1 CXCL2 | No improvement in BBB leakage, infarct volume, or functional outcome | (206) | |
| Anti-CKLF1 antibody | CKLF1 | Decreased BBB permeability | (207) | |
| Adhesion interferes | Anti-ICAM-1 antibody/antisense oligonucleotides | ICAM-1 | Decreased infarct volume and neurological deficit | (208) |
| Anti-MAC-1 antibody (Hu23F2G) | Mac-1 | Reduced ischemic injury | (209) | |
| Anti-E-selectin antibody | E-selectin | Decreased infarct volume and neurological deficit | (210) | |
| Anti-P-selectin antibody | P-selectin | Decreased BBB leakage, infarct volume, and neurological deficit | (211) | |
| anfibatide | GPIbα | (43) | ||
| JAM-Ap | JAM-A | (212) | ||
| Deleterious factor neutralization | KYC | MPO | (213) | |
| Anti-lipocalin-2 antibody | lipocalin-2 | (65) | ||
| melatonin | MMP9 | (214) | ||
| S-oxiracetam | (215) | |||
| alpha-1 antitrypsin | elastase | Decreased infarct volume and neurological deficit | (216) | |
| Polarization regulation | All trans-retinoic acid | STAT1 | (217) | |
| bexarotene | RXR/PPARγ | Decreased BBB leakage and infarct volume, improved neurological outcome | (218) | |
| rosiglitazone | PPARγ | (73) |
CXCR1, C-X-C chemokine receptor 1; CXCR2, C-X-C chemokine receptor 2; CXCL1 CXC chemokines ligand 1; CXCL2, CXC chemokines ligand 1; BBB, blood-brain barrier; CKLF1, chemokine-like factor 1; G31P, ELR-CXC, CXC chemokines bearing the glutamic acid-leucine-arginine; ICAM-1, intercellular adhesion molecule-1; MAC-1, macrophage-1 antigen; GPIbα, glycoprotein Ib alpha; JAM-Ap, JAM-A antagonist peptide; JAM-A, Junctional adhesion molecule-A; KYC, N-acetyllysyltyrosylcysteine amide; MPO, myeloperoxidase; STAT1, signal transducer and activator of transcription; RXR/PPARγ, retinoid X receptors/peroxisome proliferator-activated receptor gamma.