Table 1A. Studies on the neuroprotective or neurotoxic effect of TNF in experimental stroke.
| Ischemia model | Strain | Intervention | Results | Effect of TNF | Reference |
|---|---|---|---|---|---|
| Mouse | |||||
| Distal pMCAO (electrocoagulation) | BALB/c | Intracisternal injection of 0.5 μg TNF 48 hours before occlusion | Intracisternal administration decreased infarct volume | Neuroprotective | Nawashiro et al (1997c) |
| Distal pMCAO (electrocoagulation) | BALB/c | i.p. or i.v. injection of 3 mg/kg TNF-bp immediately after occlusion | TNF-bp decreased infarct volume in a dose-dependent manner in all experiments | Neurotoxic | Nawashiro et al (1997a) |
| Distal pMCAO (electrocoagulation) | BALB/c | Topic administration of 3 mg/kg TNF-bp immediately and 1 hour after occlusion | TNF-bp decreased infarct volume at 1 hour, 24 hours and 2 weeks | Neurotoxic | Nawashiro et al (1997b) |
| Distal pMCAO (electrocoagulation) | TNF-KO, C57BL/6, B6129 TNF-RI-KO, TNF-RII-KO, TNF-RI/RII-KO, C57x129 TNF-KO → TNF-KO TNF-KO → C57BL/6 C57BL/6 → TNF-KO C57BL/6 → C57BL/6 | — | TNF-KO displayed larger infarcts compared with C57BL/6 and B6129 at 24 hours and 5 days TNF-RI-KO displayed larger infarcts compared with TNF-RII-KO, TNFRI/RII-KO, and C57x129 TNF-KO → TNF-KO and C57BL/6 → TNF-KO displayed larger infarcts compared with TNF-KO → C57BL/6 and C57BL/6 → C57BL/6 | Neuroprotective | Lambertsen et al (2009) |
| Distal pMCAO (electrocoagulation) | TNF-RI-KO C57BL/6 | — | TNF-RI-KO displayed larger infarcts compared with control at 24 hours, but not at 3 and 6 hours | Neuroprotective | Taoufik et al (2007) |
| Distal tMCAO (1 hour, filament) | TNF-RI/RII-KO, C57BL/6(B6), B6x129F | — | TNF-RI/RII-KO displayed larger infarcts compared with C57BL/6 and B6x129F | Neuroprotective | Bruce et al (1996) |
| Distal tMCAO (1 hour, filament) | TNF-RI-KO, TNF-RII-KO, TNF-RI/RII-KO, C57BL/6 | — | TNF-RI-KO and TNF-RI/RII-KO mice display larger infarcts compared with TNF-RII-KO and C57BL/6 | Neuroprotective | Gary et al (1998) |
| Distal tMCAO (1 hour, filament) | CD-1 | i.c.v. injection of 300 μg/kg anti-TNF-Ab 1 hour after occlusion | Anti-TNF-Ab decreased infarct volume | Neurotoxic | Yang et al (1998, 1999) |
| Rat | |||||
| Distal tMCAO (80 and 160 minutes) | SHR | 2.5 pmol TNF pre-treatment 24 hours before occlusion | TNF increased infarct volume | Neurotoxic | Barone et al (1997) |
| Distal pMCAO (occluded and cut) | SHR | 2.5 and 25 pmol TNF pre-treatment 24 hours before occlusion 10 μg TNF mAb or 12.5 μg sTNF-RI, 30 minutes before and 3 and 6 hours after occlusion | TNF increased infarct volumes in a dose-related manner. This was reversed by injection of 60 pmol TNF mAb TNF mAb and sTNF-RI reduced infarct volumes | Neurotoxic | Barone et al (1997) |
| Distal pMCAO (thromboembolic) | SD | 30 mg/kg TACE-inhibitor (DHP-067517), 15 minutes before and 6 hours after occlusion | TACE-inhibitor decreased infarct volume | Neurotoxic | Wang et al (1994) |
| Proximal tMCAO (1 hour, filament) | SD | i.v. injection of 0.36 mg/kg anti-TNF Ab 1 hour before occlusion | Anti-TNF-Ab reduced infarct volume | Neurotoxic | Lavine et al (1998) |
| Distal pMCAO (electrocoagulation) | SHR | i.v. injection of 1 mg/kg TNF-bp 30 minutes pre- or post- occlusion | TNF-bp reduced infarct volumes | Neurotoxic | Dawson et al (1996) |
Ab, antibody; i.c.v., intracerebroventricular; i.p., intraperitoneal; i.v., intravenous; KO, knock out; pMCAO, permanent middle cerebral artery occlusion; rh, recombinant human; s.c., subcutaneous; SD, sprague dawley; SHR, spontaneously hypertensive rats; tMCAO, transient middle cerebral artery occlusion; TNF, tumor necrosis factor; TNF-bp, TNF-binding protein; TNF-RI, TNF receptor I; TNF-RII, TNF receptor II; WT LM, wild-type littermates.