Table 1.
Viral gene delivery in animal models of stroke.
| Protein | Viral vector | Administration (pre-/post-injury) | Stroke model | Neuroprotective | Reference |
|---|---|---|---|---|---|
| Bcl-XL | Ad | 7 days pre- | Mouse; 30 min or 2 h MCAO | Yes | Kilic et al., 2002 |
| Bcl-2 | Lentivirus | 3 weeks pre- | Rat; NMDA in hippocampus | Yes | Wong et al., 2005 |
| HSV | 24 h pre- | Rat; permanent MCAO | Yes | Linnik et al., 1995 | |
| HSV | 30 mins post- | Rat; 1 h MCAO | Yes | Lawrence et al., 1997 | |
| HSV | 1.5 h post- | Rat; 1 h MCAO | Yes | Yenari et al., 2001 | |
| HSV | 4 h post- | Rat; 1 h MCAO | No | Lawrence et al., 1997 | |
| Bcl-w | rAAV | 3 weeks pre- | Rat; 1.5 h MCAO | Yes | Sun et al., 2003 |
| BDNF | rAAV | 4–5 weeks pre- | Rat; 30 min MCAO | Yes | Andsberg et al., 2002 |
| rAAV | 14 days pre- | Rat; various MCAO models | Yes | Zhang et al., 2011 | |
| CDNF | rAAV | 2 days post- | Rat; 1 h bilateral CCA and right MCAO | No | Matlik et al., 2014 |
| CNTF | Ad | 7 days pre- | Mouse; 30 min MCAO | Yes | Hermann et al., 2001b |
| GDNF | Lentivirus | 3 weeks pre- | Rat NMDA to hippocampus | Yes | Wong et al., 2005 |
| Ad | 7 days pre- | Mouse; 30 min MCAO | Yes | Hermann et al., 2001a,b | |
| HSV | 4 days pre- and | Rat; 1 h MCAO | Yes | Harvey et al., 2003 | |
| HSV | 3 days post- | Rat; 1 h MCAO | No, but behavioral improvement | Harvey et al., 2003 | |
| Ad | During and | Rat; 1.5 h MCAO | Yes | Zhang et al., 2002 | |
| Ad | 1 h post- | Rat; 1.5 h MCAO | No | Zhang et al., 2002 | |
| rAAV | During | Rat; 1.5 h bilateral CCA and right MCAO | Yes | Tsai et al., 2000, 2006 | |
| HB-EGF | rAAV | 6–7 days post- | Rat; 80 min MCAO | No, but functional recovery with neurogenesis and angiogenesis | Sugiura et al., 2005 |
| NGF | rAAV | 4–5 weeks pre- | Rat; 30 min MCAO | Yes | Andsberg et al., 2002 |
| NT3 | rAAV | 24 h post- | Rat; endothelin-1 | No, but improved behavioral and sensory outcomes | Duricki et al., 2016 |
| HSP-27 | HSV | 3 days pre- | Rat; 30 min MCAO | Yes | Badin et al., 2006 |
| HSV | 30 mins post- | Rat; 30 min MCAO | Yes | Badin et al., 2009 | |
| HSP-70 | HSV | 3 days pre- | Rat; 30 min MCAO | No | Badin et al., 2006 |
| HSV | 30 mins post- | Rat; 30 min MCAO | No | Badin et al., 2009 | |
| HSP-72 | HSV | 24 h pre- | Rat; 1 h MCAO | Yes | Yenari et al., 1998 |
| HSV | 17 h pre- | Rat; 8 min bilateral CCA | Yes | Kelly et al., 2002 | |
| HSV | 0.5 and 2 h post- | Rat; 1 h MCAO | Yes | Hoehn et al., 2001 | |
| HSV | 5 h post- | Rat; 1 h MCAO | No | Hoehn et al., 2001 | |
| Gpx | HSV | 12 h pre- | Rat; 1 h MCAO | Yes | Hoehn et al., 2003 |
| 2 and 5 h post- | Rat; 1 h MCAO | Yes | Hoehn et al., 2003 | ||
| CXCL12 (SDF-1α) | Ad | 3 days pre- and | Rat; 1.5 h MCAO | Yes | Yoo et al., 2012 |
| Ad | 7 days post- | Rat; 1.5 h MCAO | Yes | Yoo et al., 2012 | |
| rAAV | 7 days post- | Mouse; permanent MCAO | Protects myelin sheath | Li et al., 2015 | |
| rAAV | 7 days post - | Mouse; permanent MCAO | Yes | Li et al., 2014 | |
| IL-1 receptor antagonist | rAAV | During | Rat; 1.5 h bilateral CCA and right MCAO | Yes | Tsai et al., 2003 |
| Netrin-1 | rAAV | 1 day post- | Rat; 1 h bilateral CCA and left MCAO | No, but increased vascularisation and improved behavior | Sun et al., 2011 |
The efficacy of gene therapy as a treatment option following stroke, to facilitate the expression of various proteins, has been assessed in several animal models of stroke with the administration of viral vectors tested both pre- and post-ischemia. Outcomes of neuroprotection varied between infarct volume and neuronal cell counts. Ad, adenovirus; rAAV, recombinant adeno-associated virus; BDNF, brain derived neurotrophic factor; CCA, common carotid artery; CDNF, cerebral dopamine neurotrophic factor; CNTF, ciliary neurotrophic factor; CXCL – CXC chemokine ligand; GDNF, glial cell-derived neurotrophic factor; Gpx, glutathione peroxidase; HB-EGF, heparin-binding epidermal growth factor-like growth factor; HSP, heat shock protein; HSV, herpes simplex virus; MCAO, middle cerebral artery occlusion; NMDA, N-methyl D-aspartate; NT, neurotrophin; SDF, stromal cell-derived factor.