Table 1.
Pharmacological approaches to augment proliferation and/or migration of SVZ-derived NPCs in the uninjured and injured rodent brain.
| Neurotrophic factor or signaling peptide (alphabetical) | Administration | Species | Type of injury | In vivo treatment effect | Evaluation method | References |
|---|---|---|---|---|---|---|
| Ang1 | SC administration for 7 days beginning 1 day post-injury | Mice | Experimental stroke (MCAO) | Increased DCX-positive neuroblasts in the injured cortex | DCX | (132) |
| BDNF | IV administration for 5 days beginning 1 h post-injury | Rats | Experimental stroke (photothrombotic) | Increased DCX-positive neuroblast migration from the SVZ to the ipsilateral striatum but not to the ischemic cortex | DCX | (133) |
| EGF | IV administration for 6 days | Mice | Uninjured | Increased SVZ NPC proliferation; increased neuroblast migration away from LV walls; differentiation into BrdU/NeuN-positive neurons and BrdU/S100-positive glial cells | lacZ reporter gene, [3H] thymidine, BrdU, NeuN, S100 | (134) |
| EGF | IV administration for 14 days | Rats | Uninjured | Increased SVZ NPC proliferation; increased BrdU-positive cells in the striatum 4 weeks post-infusion | BrdU | (135) |
| EGF | IV administration for 7 days beginning 2 days post-injury | Mice | Experimental stroke (MCAO) | Increased DCX/BrdU-positive SVZ NPC proliferation; migration of DCX/BrdU-positive cells to the injured striatum and maturation into PV-containing interneurons | DCX, BrdU, PV | (136) |
| EGF and EPO | IV administration of EGF for 7 days followed by EPO for 7 days beginning 4 days post-injury | Rats | Experimental stroke (focal PVD) | Increased BrdU-positive NPC migration from the SVZ to the injured cortex; differentiation into BrdU/NeuN-positive neurons and BrdU/GFAP-positive glial cells in the injured cortex | BrdU, NeuN, GFAP | (137) |
| EGF and FGF-2 | IV co-administration for 3 days beginning 1 day post-injury | Rats | Experimental stroke (MCAO) | Increased BrdU-positive SVZ NPC proliferation | BrdU | (138) |
| EGF and NGF | IV co-administration for 4 days followed by single infusion of NGF 4 days later | Mice (Aged) | Uninjured | Increased Ki-67-positive SVZ NPC proliferation | Ki-67 | (139) |
| EPO | IV administration for 6 days | Mice | Uninjured | Increased migration of BrdU-positive NPCs from the SVZ to the OB; increased BrdU/TH-positive neurons in the OB | BrdU, TH | (140) |
| FGF-2 | IV administration for 14 days | Rats | Uninjured | Increased SVZ NPC proliferation; increased BrdU-positive cells in the OB 4 weeks post-infusion | BrdU | (135) |
| G-CSF | SC administration for 15 days beginning 1-h post-injury | Rats | Experimental stroke (MCAO) | Increased BrdU-positive SVZ NPC proliferation; subset of cells was BrdU/NeuN-positive | BrdU, NeuN | (141) |
| IL-15 | Single IV administration | Mice | Uninjured | Increased BrdU-positive and DCX-positive SVZ NPCs | BrdU, DCX | (142) |
| NAME (NOS inhibitor) | Single IV administration | Rats | Uninjured | Increased BrdU-positive cells in the SVZ, RMS, and OB | BrdU | (143) |
| NGF | Single administration in the form of eye drops | Rats | Uninjured | Increased Ki-67-positive SVZ NPC proliferation | Ki-67 | (144) |
| PKRA7 (PROK2 antagonist) | IP administration for 4 days beginning 1 h post-injury | Mice | Blunt force TBI | Decreased BrdU-positive neuroblast migration from the SVZ to the injured cortex | BrdU | (145) |
| PROK2 | Single intracortical administration | Mice | Uninjured | Increased BrdU-positive cells in the cortex | BrdU | (145) |
| SDF-1 | SC administration for 7 days beginning 1 day post-injury | Mice | Experimental stroke (MCAO) | Increased DCX-positive neuroblasts in the injured cortex | DCX | (132) |
| TGF-1 | IN administration 2 and 24 h post-injury | Mice | Experimental stroke (MCAO) | Increased BrdU-positive cells in the SVZ and injured striatum; increased BrdU/DCX/NeuN-positive cells in the striatum | BrdU, DCX, NeuN | (146) |
| VEGF | IV administration for 3 days beginning 1 day post-injury | Rats | Experimental stroke (MCAO) | Increased BrdU-positive SVZ NPC proliferation | BrdU | (147) |
SVZ, subventricular zone; NPC, neural precursor cell; OB, olfactory bulb; IV, intraventricular; IP, intraperitoneal; IN, intranasal; SC, subcutaneous; LV, lateral ventricle; EGF, epidermal growth factor; FGF, fibroblast growth factor; EPO, erythropoietin; NGF, nerve growth factor; BDNF, brain-derived neurotrophic factor; TGF, transforming growth factor; G-CSF, granulocyte-colony stimulating factor; VEGF, vascular endothelial growth factor; SDF, stromal derived factor; ang, angiopoietin; PROK2, prokineticin 2; IL, interleukin; NAME, Nω-nitro-methyl-L[D]-arginine-methyl ester; NOS, nitric oxide synthase; PVD, pial vessel disruption; MCAO, middle cerebral artery occlusion; PV, parvalbumin; TH, tyrosine hydroxylase; DCX, doublecortin.