Table 2 Candidate acute and 3-month protein markers statistically significantly associated to neurological outcome in the present study, for which experimental ischemic stroke models provide evidence or suggestion of a causal influence on functional outcome.
Protein | Full protein name | Gene, localisation | Highest expression (GTEx) | Ischemic stroke outcome study | ||||
|---|---|---|---|---|---|---|---|---|
Animal model | Clinical study | |||||||
Knockout | Induced overexpression or agonistic treatment | Induced inactivation, down-regulation or inhibition | Other | |||||
Proteins inversely associated to the NIH Stroke Scale | ||||||||
NTRK2 | BDNF/NT-3 growth factors receptor Common alias: Tropomyosin-Related Kinase B (TrkB) | NTRK2, 9q21 | Brain | Interference in isoform processing: improved neurological outcome, reduced infarct size33 | Candidate NTRK2 SNPs associated to neurological outcome35 and post-stroke depression36,37. Low blood levels of BDNF (ligand) associated to poor functional outcome2,8,9,10 | |||
Treatment with Neurotrophin-3 (ligand): improved sensorimotor recovery38,39 | ||||||||
NTRK3 | NT-3 growth factor receptor | NTRK3, 15q25 | Arterial tissue | |||||
DDR1 | Epithelial discoidin domain-containing receptor 1 | DDR1, 6p21 | Brain | Improved neurological outcome, reduced infarct size40 | Treatment with Imatinib (non-selective inhibition): improved neurological outcome41, varying effects on infarct size41,42,43 | Imatinib added to iv thrombolysis: possible effect on functional outcome (phase II trial)44. Phase III ongoing (Clinical Trials/NCT03639922) | ||
PDGF-R-alpha | Platelet-derived growth factor receptor alpha | PDGFRA, 4q12 | Ovary | |||||
RGMA | Repulsive guidance molecule A | RGMA, 15q26 | Esophagus | |||||
BCAN | Brevican core protein | BCAN, 1q23 | Brain | Four-gene KO: delayed sensorimotor recovery within first 14 days, no effect on infarct size47 | ||||
NCAN | Neurocan core protein | NCAN, 19p13 | Brain | Direct delivery (infarct cavity): no effect on functional outcome48 | ||||
CD38 | ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 | CD38, 4p15 | Spleen | Improved neurological recovery, reduced infarct size49 | Day 5 intraventricular siRNA administration: Poorer neurological outcome, no effect on infarct size50 | |||
GDF-8 | Growth/differentiation factor 8 | MSTN, 2q32 | Cervix | Improved skeletal muscle restoration and motoric recovery51 | ||||
CD200R1 | Cell surface glycoprotein CD200 receptor 1 | CD200R1, 3q13 | Spleen | Poorer neurological outcome, no effect on infarct size30 | Inhibited functional recovery52 | |||
Protein positively associated to the NIH stroke scale | ||||||||
NMNAT1 | Nicotinamide/nicotinic acid mononucleotide adenylyl-transferase 1 | NMNAT1, 1p36 | Thyroid gland | Increased infarct size54 | ||||
