Table 1. Results of meta-analysis of efficacy of therapies tested alone and in combination with a second therapy in animal models of ischemic stroke.
| Therapy | Tested with (NP/NA) | NP/NA | Q | Time M (Med) | Stroke models | Species |
Therapeutic efficacy infarct (neurological score) |
|||
|---|---|---|---|---|---|---|---|---|---|---|
| Alone | Additive | Combined | Synergy | |||||||
| M±s.e. | M±s.e. | M±s.e. | M±s.e. | |||||||
| Pharmacological neuroprotection | 231/242 | 4 | −738 (45) | 22±1 (14±1) | 18±0 (25±1) | 41±1 (41±1) | −10±1 (−4±1) | |||
| 1,5-Isoquinolinediol (ISO) | FeTMPyP (1/1) | 1/1 | 6 | 60 | Filament | Rat | 61±5 (60±12) | 28±2 (20±10) | 82±5 (59±12) | −33±2 (−41±10) |
| 3-Aminobenzamide | Melatonin (1/1), z-VAD-fmk (1/1) | 2/2 | 4 | 45 | Filament | Rat | 45±7 (41±11) | 16±2 (21±2) | 82±6(62±11) | −37±2 (−20±2) |
| AG490 | DMTU (1/1) | 1/1 | 5 | −20 | Filament | Rat | 32±9 | 39±5 | 65±8 | 7±5 |
| Albumin | tPA (1/1) | 1/1 | 5 | 120 | Filament | Rat | 43±17(42±19) | 61±16 (39±14) | 18±18 (14±17) | 18±16 |
| Alcohol | Caffeine (2/2) | 2/2 | 5 | −75 | Clip/wire | Rat | −69±10 | 99±9 | 74±5 | 170±12 |
| Alpha –PBN | tPA (0/1) | 0/1 | 4 | 360 | Embolic | Rat | — | 30±9 | 6±9 | — |
| Ang-1 | Stem cells (0/1) | 0/1 | 3 | 360 | Filament | Rat | — | 1±5 | 38±5 | — |
| Anti-CD 18 | tPA (2/2) | 2/2 | 4 | 120 | Embolic | Rat | 26±12 (0±71) | 23±10 (0±24) | 30±12 (50±71) | −3±10 (0±24) |
| Atorvastatin | Hypothermia (3/3), tPA (1/1) | 4/4 | 5 | −10,740 | Filament, embolic | Rat | 36±3 (19±6) | 38±3 (30±6) | 63±3 (40±6) | 2±3 |
| Basic fibroblast growth factor (BFGF) | Citicholine (1/1), Heparin (1/1), z-DEVD.FMK (2/1), z-VAD.FMK (1/1) | 5/4 | 6 | 30 | Filament | Mice, rat | 3±6 (10±2) | 37±6 (47±2) | 41±6 (52±3) | 38±6 (35±3) |
| Batroxobin | Urokinase (2/2) | 2/2 | 2 | 120 | Filament | Rat | 50±15 (−3±50) | 61±8 (−17±39) | 27±15 (−55±52) | −69±9 (−8±27) |
| BB-823 | Sipatrigine (1/1) | 1/1 | 4 | −15 | Filament | Rat | 29±20 (24±24) | 6±18 (53±20) | 47±16 (25±23) | −23±18 (29±32) |
| BDNF | Hypothermia (1/1), Ox26 (2/2), stem cells (1/1) | 4/4 | 5 | 398 | Filament | Rat | 14±5 | 18±3 | 43±5 | 0±3 |
| Butoxamine | Clenbuterol (1/2) | 1/2 | 3 | −300 | Coagulation | Mice | −2±6 | −8±4 | −1±6 | −11±6 |
| Cadesartan | Pioglitazone (1/1), Rosuvastatin (2/2) | 3/3 | 6 | −1,960 | Filament | Rat | 61±4 (44±5) | 19±4 (9±6) | 54±5 (37±6) | −42±4 (−36±6) |
| Caffeine | Alcohol (2/2), CNS-1102 (0/1), MK801 (0/1), MgSO4 (0/1) | 2/5 | 5 | −180 | Clip/wire | Rat | −21±18 | 88±6 | 78±16 | 170±12 |
| Citicholine | BFGF (1/1), Lamotrigine (2/2), MK801 (2/2), Nimodipine (1/1), tPA (7/7), Urokinase (1/1) | 14/14 | 4 | 60 | Filament, embolic, clip/ligation | Rat | 22±3 (6±8) | 17±2 (1±6) | 45±3 (24±8) | −12±2 (−4±6) |
| Clenbuterol | Butoxamine (2/1), Memantine (9/9) Metoprolol (2/1), Propranolol (1/1) | 14/12 | 2 | −6 | Electrocoagulation | Mice | 8±1 | 7±1 | 17±1 | 1±1 |
| CNS-1102 | Caffeine (1/0) | 1/0 | 4 | 15 | Wire/clip | Rat | 42±22 | — | 92±17 | — |
| CP101,606-27 | tPA (2/1) | 2/1 | 4 | 120 | Embolic | Rat | 63±11 (17±8) | 15±10 (−11±12) | 57±11 (11±9) | −57±10 (−26±13) |
| Cycloheximide | Dextrorphan (1/1) | 1/1 | 2 | −18 | Clip/ligation | Rat | 52±13 | 34±16 | 87±11 | −18±16 |
| Cyclosporine-A | Methylprednisolone (2/2) | 2/2 | 5 | 180 | Filament | Rat | 2±9 (−2±3) | −4±7 (−1.3±5) | −1±8 (−3±5) | −7±7 (7±5) |
| DETA NONOate | Stem cells (2/2) | 2/2 | 6 | 1,440 | Filament | Rat, mice | 11±29 (13±31) | 6±16 (5±13) | 23±26 (42±30) | −4±16 (−7±13) |
| Dexamethasone | Mannitol (0/1) | 0/1 | 1 | 0 | Implanted occluder | Cat | — | −4±9 | −5±9 | — |
| Dexanabinol | Tempol (2/2) | 2/2 | 5 | 60 | Electrocoagulation | Rat | 54±12 (72±18) | −2±8 (29±15) | 47±11 (77±16) | −56±8 (−44±15) |
| Dextromethorphan | Tirilazad (1/1) | 1/1 | 7 | −15 | Filament | Rat | 45±14 | −36±12 | 12±16 | −80±12 |
| Dextrorphan | Cycloheximide (1/1) | 1/1 | 2 | −15 | Clip/ligation | Rat | 53±17 | 35±11 | 87±11 | −18±11 |
| Diaspirin crosslinked hemoglobin (DCLHb) | Lubeluzole (1/1) | 1/1 | 4 | 15 | Clip | Rat | 11±3 | 19±3 | 72±3 | 8±3 |
| Dizocilpine | Caffeine (1/1), Citicholine (2/2), EG761 (1/1), Hypothermia (1/1), Muscimol (2/2), NBQX (1/1), Nimodipine (1/0), RSR13 (2/1), tPA (1/1), zVAD-fmk (7/7) | 18/16 | 5 | 32 | Filament, clip/wire/ligation, embolic, electrocoagulation | Rat, mice, cat, gerbil | 21±4 (22±8) | 9±2 | 39±3 (56±8) | −15±2 |
| Dimethylthiourea | AG490 (1/1) | 1/1 | 5 | −60 | Filament | Rat | 26±8 | 33±5 | 65±8 | 7±5 |
| DtBHB | -NAME (1/1) | 1/1 | 2 | 240 | Filament | Rat | −4±24 | 49±24 | 45±26 | 53±24 |
| Edavarone | Normobaric hyperoxia (1/1), tPA (0/1) | 1/2 | 4 | 2 | Filament | Rat, mice | 13±16 (16±20) | 29±7 (8±17) | 45±17 (58±21) | 8±14 |
| EGb 761 | Dipyrone (2/2), FK506 (1/0), MgSO4 (1/0), MK801 (1/0) | 5/2 | 4 | −10,092 | Filament, ligation | Rat, gerbil | 18±5 | −3±5 | 17±4 | −14±5 |
| Eliprodil | tPA (1/1) | 1/1 | 4 | 10 | Embolic | Rat | 49±40 (48±18) | 31±22 (16±12) | 88±36 (70±18) | −18±22 (−32±12) |
| Enlimolab | tPA (0/1) | 0/1 | 4 | 240 | Embolic | Rat | — | 35±13 | 25±13 | — |
| EPC-K1 | Heparin (1/1) | 1/1 | 5 | 180 | Photochemical | Rabbit | 28±10 (16±13) | 72±9 (129±7) | 56±8 (69±14) | 44±10 (112±13) |
| Erythropoietin (EPO) | GCSF (1/1), IGF-1 (1/1), stem cells (1/1), tPA (3/3) | 6/6 | 5 | 585 | Filament, embolic, ligation/clip | Rat, mice | 5±7 (22±38) | 4±5 (2+29) | 14±7 (17±35) | −8±5 |
| Estrogen | Progesterone (1/1), tPA (0/1) | 1/2 | 5 | −10,080 | Filament | Rat | 63±26 | 64±12 | 67±26 | −17±21 |
| Ethyl pyruvate | Aspirin (4/4) | 4/4 | 5 | 413 | Filament | Rat | 71±11 (67±29) | 20±4 | 74±11 (78±29) | −55±4 |
| FeTMPyP | 1,5-Isoquinolinediol (1/1) | 1/1 | 6 | 115 | Filament | Rat | 54±5 (39±13) | 21±1 (−1±8) | 82±5 (59±12) | −33±1 (−41±8) |
| Fluosol | Risperidone (1/0) | 1/0 | 1 | 0 | Balloon occlusion | Cat | −171±64 | — | 6±16 | — |
| Fluoxetine | Risperidone (1/1) | 1/1 | 4 | −10,080 | Photochemical | Rat | −34±36 | −30±19 | −16±32 | 4±19 |
| Glucose | Insulin (0/1) | 0/1 | 3 | −50 | Electrocoagulation | Rat | − | −20±4 | −7±6 | — |
| Glyercol | NS-7 (1/1) | 1/1 | 5 | 5 | Electrocoagulation | Rat | 20±16 | −1±11 | 64±16 | −21±11 |
| Granulocyte colony stimulating factor | EPO (1/1), stem cells (0/1), tPA (1/1) | 2/3 | 5 | 750 | Embolic, clip/ligation, cauterization | Rat, mice | 55±5 | −4±4 | 63±5 | −33±22 |
| IGF-1 | EPO (1/1) | 1/1 | 7 | 60 | Filament | Mice | 22±20 | 23±11 | 55±17 | 1±11 |
| Insulin | Glucose (1/0), Hypothermia (1/1), MgCl2 (0/1), tPA (1/1) | 3/3 | 3 | −30 | Embolic, electrocoagulation | Rat | 15±4 | 11±3 | 15±4 | −12±5 |
| Isoflurane | z-IETD-fmk (1/1), zVAD-fmk (1/1) | 2/2 | 7 | 8 | Filament | Rat | 9±11 | 31±6 | 70±9 | 23±6 |
| Ketamine | Nicotinamide (1/1) | 1/1 | 3 | −10 | Filament | Rat | −4±8 | 68±12 | 63±5 | 72±12 |
| Lamotrimine | Citicholine (2/2) | 2/2 | 7 | 90 | Filament | Rat | 14±12 (25±10) | 5±6 (22±5) | 45±12 (24±9) | −10±6 (−1±5) |
| -Name | DtBHB (1/1) | 1/1 | 2 | 240 | Filament | Rat | −4±27 | 49±21 | 45±26 | 53±21 |
| Lubeluzole | DCLHb (1/1) | 1/1 | 4 | 15 | Clip | Rat | 53±3 | 61±3 | 72±3 | 8±3 |
| Magnesium chloride (MgCl2) | Insulin (1/0), Tirilazad (1/1) | 2/1 | 6 | −10 | Electrocoagulation, filament | Rat | 26±6 | 11±10 | 46±5 | −14±10 |
| Magnesium sulphate (MgSO4) | Caffeine (1/0), EGB761 (0/1), FK506 (1/1), Hypothermia (1/1), Mexiletine (1/1), Nicardipine (0/1) | 4/5 | 4 | 28 | Filament, ligation, wire/clip | Rat, gerbil, | 23±9 | 18±3 | 44±9 | −11±7 |
| Mannitol | Dexamethasone (1/1), Fluosol (1/1), Hypothermia (1/1), Tirilazad (1/1) | 4/4 | 4 | −1 | Filament, electrocoagulation, balloon occlusion | Rat, cat, rabbit | 11±4 (49±13) | 11±3 (21±9) | 40±4 (83±10) | −5±3 (−27±9) |
| MC-1 | tPA (1/1) | 1/1 | 3 | 60 | Embolic | Rat | 37±16 (17±58) | 3±11 (−17±48) | 41±14 (17±59) | −34±11 (−33±48) |
| Melatonin | 3-AB (1/1), Meloxicam (1/1), Nicotinamide (0/1), tPA (1/1) | 3/4 | 4 | 68 | Filament | Rat, mice | 45±8 (41±11) | 23±2 (21±2) | 60±8 (62±11) | −33±2 (−20±2) |
| Meloxicam | Melatonin (1/1) | 1/1 | 3 | 240 | Filament | Rat | 23±16 | 18±8 | 64±15 | −5±8 |
| Memantine | Clenbuterol (9/9) | 9/9 | 2 | −3 | Electrocoagulation | Mice | 11±2 | 16±2 | 19±2 | 5±2 |
| Methohexital | Hypothermia (1/1) | 1/1 | 5 | −30 | Filament | Rat | 32±25 (38±23) | −4±10 (−8±23) | 66±24 (69±22) | −36±10 (−50±23) |
| Methylprednisolone | Cyclosporine (2/2) | 2/2 | 5 | 180 | Filament | Rat | 3±9 (−2±3) | −4±6 (−1±5) | −1±8 (−3±5) | −7±6 (1±5) |
| Metoprolol | Clenbuterol (1/2) | 1/2 | 3 | −300 | Coagulation | Mice | 5±4 | 4±3 | 24±3 | 3±4 |
| Mexiletine | MgSO4 (1/1) | 1/1 | 4 | −60 | Filament | Rat | 36±17 | −17±19 | 16±16 | −53±19 |
| Minocycline | Hypothermia (2/2), tPA (1/2) | 3/4 | 4 | 120 | Filament, embolic | Rat | 29±6 (50±13) | 29±4 (34±7) | 49±6 (54±13) | −15±4 (−13±8) |
| Muscimol | Dizocilpine (2/2) | 2/2 | 6 | 123 | Embolic, filament | Rat | 7±32 | −16±14 | 30±30 | −12±14 |
| NBQX | Dizocilpine (1/1), tPA (2/2) | 3/3 | 3 | 0 | Embolic, electrocoagulation | Rat, mice | 23±4 | 7±3 | 29±5 | −17±3 |
| NEP 1-40 | Motor training (1/1) | 1/1 | 4 | 10,080 | ET-1 | Rat | −5±20 | 5±20 | −9±21 | 10±20 |
| Nerve growth factor (NGF) | Electroacupuncture (1/1) | 1/1 | 6 | 120 | Filament | Rat | 21±15 (23±11) | 34±9 (21±5) | 59±15 (44±11) | 13±9 |
| Nicardipine | Magnesium sulphate (1/0) | 1/0 | 3 | −120 | Electrocoagulation, filament | Rat | 58±10 | — | 79±9 | — |
| Nicotinamide | Ketamine (1/1), Melatonin (1/0) | 2/1 | 4 | 75 | Filament | Rat | 33±8 (44±13) | 67±9 | 67±4 (59±12) | 72±9 |
| Nimodipine | Citicholine (1/1), MK801 (0/1) | 1/2 | 4 | 45 | Clip/ligation | Rat, cat, rabbit | 34±19 | 18±5 | 60±19 | −17±9 |
| NS-7 | Glycerol (1/1) | 1/1 | 5 | 5 | Electrocoagulation | Rat | 65±16 | 44±11 | 64±16 | −21±11 |
| Ox26 | BDNF (2/2) | 2/2 | 5 | 60 | Filament | Rat | −1±16 | 46±7 | 54±8 | 47±7 |
| Pentasaccharide | tPA (1/1) | 1/1 | 7 | 10 | Embolic | Rat | 6±17 | −40±7 | 40±17 | −46±7 |
| Pioglitazone | Candesartan (1/1) | 1/1 | 5 | −7,200 | Filament | Rat | 43±9 (30±16) | −4±12 (5±18) | 39±11 (32±18) | −47±12 (−25±18) |
| Pravastatin | tPA (1/1) | 1/1 | 0 | −40,320 | Filament | Rat | 65±5 | 61±4 | 81±5 | −4±4 |
| Progesterone | Estrogen (1/1) | 1/1 | 5 | −30 | Filament | Rat | 21±31 | 4±12 | 67±26 | −17±12 |
| Propranolol | Clenbuterol (1/1) | 1/1 | 3 | −300 | Electrocoagulation | Mice | −2±6 | −18±5 | −12±6 | −16±5 |
| PS519 | tPA (3/2) | 3/2 | 5 | 240 | Embolic | Rat | 25±16 (44±17) | 37±9 (29±13) | 44±17 (46±16) | −2±9 (−27±13) |
| Qingpi | Hypothermia (1/1) | 1/1 | 3 | 120 | Filament | Rat | 41±28 (32±17) | 22±15 (12±13) | 65±22 (40±15) | −19±15 (−20±13) |
| Rapamycin | Tacrolimus (1/1) | 1/1 | 4 | −20 | Filament | Rat | 5±23 | −62±15 | −18±24 | −67±15 |
| Risperidone | Fluoxetine (1/1) | 1/1 | 4 | −10,080 | Photochemical | Rat | 14±31 | 18±27 | −16±32 | 4±27 |
| Rosiglitazone | tPA (0/2) | 0/2 | 3 | −20,160 | Embolic | Rat | — | 9±2 | 38±3 | — |
| Rosuvastatin | Candesartan (2/2), tPA (1/1) | 3/3 | 5 | −6,690 | Filament | Rat, mice | 36±5 (29±7) | −6±4 (−7±4) | 55±5 (38±7) | −43±4 (−36±4) |
| RSR13 | Dizocipline (1/2) | 1/2 | 6 | −30 | Filament | Rat | 15±16 | 19±6 | 72±10 | 6±9 |
| S-0139 | tPA (1/1) | 1/1 | 7 | 120 | Embolic | Rat | 19±2 (45±4) | 30±2 (48±3) | 28±2 (57±4) | 12±2 |
| Simvastatin | Stem cells (1/1) | 1/1 | 7 | 1,440 | Not stated | Rat | 16±26 (15±17) | 13±22 (36±17) | 38±26 (38±17) | −3±22 |
| Sipatrimine (BW619C89) | BB-823 (1/1) | 1/1 | 4 | −15 | Filament | Rat | 41±18 (−29±21) | 18±19 (0.4±23) | 47±16 (25±23) | −23±19 (29±23) |
| Tacrolimus (FK506) | EGB761 (0/1), Hypothermia (1/1), MgSO4 (1/1), Rapamycine (1/1), tPA (5/5) | 8/9 | 4 | 83 | Filament, ligation, photochemical | Rat, gerbil | 20±4 | 13±3 | 30±4 | −7±3 |
| Tempol | Dexanabinol (2/2) | 2/2 | 5 | 60 | Electrocoagulation | Rat | 51±10 (51±19) | −9±8 (6±11) | 47±11 (77±16) | −54±8 (−42±11) |
| Tirilazad | Dextromethorphan (1/1), Mannitol (1/1), MgCl2 (1/1), tPA (2/2) | 5/5 | 6 | 22 | Electrocoagulation, embolic, filament | Rat, rabbit | 44±6 | 38±4 | 48±6 | −6±4 |
| Topiramate | Urokinase (2/2) | 2/2 | 3 | 120 | Embolic | Rat | 63±10 (40±10) | 34±7 (7±14) | 82±10 (45+14) | −29±7 (−39±14) |
| TS-011 | tPA (1/1) | 1/1 | 3 | 1 | Embolic | Primate | 26±19 (10±7) | 54±16 (12±6) | 38±22 (16±8) | 28±16 (2±6) |
| U-101033E | U-74389G (1/1) | 1/1 | 6 | −15 | Filament | Rat | 53±17 | 29±13 | 54±18 | −24±13 |
| U-74389G | U-101033E (1/1) | 1/1 | 6 | −15 | Filament | Rat | 25±18 | 1±11 | 54±18 | −24±11 |
| UK-279, 276 | tPA (2/2) | 2/2 | 7 | 180 | Embolic | Rat | 3±11 (7±9) | 44±6 (9±7) | 57±9 (22±8) | 41±6 (1±7) |
| Vapiprost | SUN9216 (0/1) | 0/1 | 3 | 60 | Photochemical | Rat | — | 14±18 | 11±17 | — |
| VEGF | Stem cells (0/1) | 0/1 | 2 | 360 | Filament | Rat | — | −42±5 | −5±6 | — |
| Velcade | tPA (1/1) | 1/1 | 6 | 120 | Embolic | Rat | 33±20 (19±12) | 40±15 (34±12) | 55±19 (36±13) | 7±15 (15±12) |
| Xg-102 | Hyperbaric oxygen (1/1), tPA (1/1) | 2/2 | 7 | 105 | Filament | Rat, mice | 46±6 (38±9) | 49±5 | 76±6 (42±14) | −6±5 (−33±15) |
| YM872 | tPA (1/1) | 1/1 | 3 | 120 | Embolic | Rat | 46±18 | 38±9 | 82±13 | −8±9 |
| z-DEVD.FMK | BFGF (2/2), Dizocipline (4/4) | 6/6 | 5 | 33 | Filament | Mice | 14±7 (3±3) | 43±5 | 45±6 (54±4) | 25±4 (44±2) |
| z-IETD-fmk | z-IETD-fmk (1/1) | 1/1 | 6 | −30 | Filament | Rat | 35±14 | 54±11 | 67±13 | 20±11 |
| zVAD-fmk | 3-AB (1/1), BFGF (1/1), Dizocilpine (3/3), Isoflurane (1/1) | 6/6 | 5 | −3 | Filament | Rat, mice | 31±7 (10±4) | 42±3 | 70±5 (48±7) | 3±4 (19±7) |
| Reperfusion therapy | 100/92 | 4 | 136 (120) | 15±1 (6±2) | 13±1 (15±1) | 35±1 (37±2) | −6±1 (10±2) | |||
| Abciximab | tPA (4/4) | 4/4 | 6 | 210 | Embolic | Rat | 36±7 (15±5) | 18±4 (23±3) | 47±7 (28±5) | −10±4 (18±3) |
| Annexin (rA2) | tPA (1/1) | 1/1 | 8 | 120 | Embolic | Rat | 2±14 | 45±13 | 49±13 | 43±13 |
| Argatroban | Hypothermia, tPA | 3/3 | 5 | 162 | Clip, embolic, filament | Rat | 5±14 | 31±8 | 35±15 | 20±8 |
| Aspirin | Ethyl pyruvate (4/4), Ticlopidine (1/1) | 5/5 | 5 | 318 | ADP ephinephrine, filament | Rat, guinea pig | 53±12 (2±13) | 3±2 (9±10) | 72±11 (37±14) | −48±2 (−10±10) |
| Cilostazol | Normobaric hyperoxia (2/2) | 2/2 | 6 | 1 | Filament | Mice | 18±13 | 33±10 | 50±12 | 16±10 |
| Clopidogrel | tPA (1/1) | 1/1 | 4 | 5 | Embolic | Rat | −2±5 (43±25) | 2±4 (−17±18) | −1±5 (30±22) | 4±4 (−60±18) |
| Dipyrone | EGB 761 (2/2) | 2/2 | 3 | −30 | Filament | Rat | 14±5 | 1±6 | 6±5 | −14±6 |
| Heparin | BFGF (0/1), EPC-K1 (1//1), Ozagrel (1/1), tPA (2/3) | 4/5 | 5 | 91 | Embolic, filament, photochemical | Rat, rabbit | −12±10 (−60±12) | 20±5 (52±14) | 55±7 (70±9) | 19±5 (112±9) |
| Melagatran | tPA (2/2) | 2/2 | 2 | 180 | Embolic | Rat | 22±10 | 17±8 | 38±11 | −8±8 |
| Ozagrel | Heparin (1/1) | 1/1 | 3 | 5 | Photochemical | Rat | 30±13 | 48±21 | 40±20 | 17±21 |
| SUN9216 | Vapiprost (1/0) | 1/0 | 3 | 60 | Photochemical | Rat | −3±7 | — | 11±17 | — |
| Ticlopidine | Aspirin (1/1) | 1/1 | 3 | −180 | ADP ephinephrine | Guinea pig | 47±37 (20±17) | 26±30 (33±15) | 47±39 (27±16) | −21±30 (13±15) |
| Tissue plasminogen activiator (tPA) | Abciximab (4/4), Albumin (1/1), Alpha-PBN (1/0), Annexin (1/1), Anti-CD18 (2/2), Aortic occlusion (1/1), Argatroban (2/2), Atorvastatin (1/1), Citicholine (7/7), Clopidogrel (1/1) , CP101,606-27 (1/2), Dizocilpine (4/1), Edaravone (1/0), Eliprodil (1/1), Enlimomab (1/0), EPO (3/3), Estrogen (1/0), GCSF (1/1), Heparin (2/2), Hypothermia (3/3), Insulin (1/1) , MC-1 (1/1), Melagatran (2/2), Melatonin (1/1), Minocycline (2/1), NBQX (1/2), Normobaric oxygen (2/2), Pentasaccharide (1/1), Pravastatin (1/1), PS519 (2/3), Rosiglitazone (2/0), Rosuvastatin (1/1), S-0139 (1/1), Tacrolimus (5/5), Tirilizad (2/2), TS-011 (1/1), UK-279,276 (2/2), Velcade (1/1), XG-102 (1/1), YM872 (1/1) | 68/63 | 4 | 138 | Filament, embolic, photochemical | Rat, mice, primate, rabbit | 15±1 (6±2) | 13±1 (12±2) | 36±1 (39±2) | −3±1 (5±2) |
| Urokinase | Batroxobin (2/2), Citicholine (1/1), Topiramate (2/2) | 5/5 | 3 | 120 | Filament, embolic | Rat | 26±7 (34±13) | 7±5 (−5±12) | 65±7 (38±14) | 19±5 (−32±13) |
| Nonpharmacological neuroprotection | 30/29 | 6 | 733 (60) | 24±2 (28±3) | 21±1 (19±2) | 50±2 (53±3) | −6±1 (−6±4) | |||
| Electroacupunture | NGF (1/1) | 1/1 | 6 | 120 | Filament | Rat | 25±15 (18±5) | 38±9 (21±5) | 59±15 (44±6) | 13±9 (3±5) |
| Exercise/environmental enrichment | NEP 1-40 (1/1), stem cells (1/1) | 2/2 | 5 | 10,080 | ET-1, cauterization | Rat | −16±6 | −3±3 | −14±6 | 13±3 |
| Hyperbaric oxygen | XG-102 (1/1) | 1/1 | 8 | 190 | Filament | Rat | 63±7 (37±9) | 34±5 | 76±6 (42±14) | −29±5 |
| Hypothermia | Argatroban (1/1), Atorvastatin (3/3), BDNF (1/1), Craniectomy (3/2), Insulin (1/1), MgSO4 (1/1), Mannitol (2/2), Methohexital (1/1), Minocycline (2/2), MK801 (1/1), Qingpi (1/1), Tacrolimus (1/1), tPA (3/3) | 21/20 | 4 | 68 | Filament, electrocoagulation, embolic | Rat | 28±2 (32±5) | 24±1 | 55±2 (59±5) | −10±1 (−10±4) |
| Normobaric oxygen | Cilostazol, Edaravone, tPA | 5/5 | 7 | 19 | Embolic, filament | Rat, mice | 15±4 (50±21) | 26±4 | 43±4 (58±21) | 10±4 |
| Surgical therapy | 3/4 | 6 | 230 (60) | 43±5 (24±12) | 40±3 (33±2) | 63±6 (36±12) | 1±5 (9±6) | |||
| Aortic occlusion | tPA (1/1) | 1/1 | 6 | 90 | Embolic | Rat | 43±20 | 21±13 | 73±17 | −21±13 |
| Craniectomy | Hypothermia (2/3) | 2/3 | 6 | 300 | Filament | Rat | 43±7 (24±12) | 42±4 (33±10) | 61±6 (36±12) | 4±5 (9±9) |
| Cellular therapy | 9/6 | 5 | 3,120 (1,440) | 22±4 (12±15) | 4±3 (22±2) | 10±3 (36±14) | 8±3 (1±23) | |||
| Stem cells | Ang-1 (1/0), BDNF (1/1), DETA-NONOate (2/2), EPO (1/1), environmental enrichment (1/1), GCSF (1/0), Simvastatin (1/1), VEGF (1/0) | 9/6 | 5 | 3,120 | Filament, cauterization | Rat, mice | 22±3 (15±14) | 4±3 (22±9) | 10±3 (36±12) | 8±3 (1±9) |
Tested with=names of the other therapies with which the therapy is tested in combination, together with the number of times it has been tested with the other therapy. NP/NA=number of experiments the therapy is tested individually as the primary therapy/number of experiments in which it is tested as the additional therapy. Q=average quality across experiments. Time=mean (median) time of delivery of the therapy postocclusion, measured in minutes. Stroke models=experimental models in which the therapy was tested. Species=species in which the therapy was tested. Therapeutic efficacy=effect size and standard error of the therapeutic efficacy derived from random effects meta-analyses. Alone=therapeutic efficacy of the treatment tested individually versus control. Additive=therapeutic efficacy of the treatment derived from the therapy in combination with another therapy versus the individual effect of the other therapy. Combined=therapeutic efficacy of the treatment in combination versus control. Synergy=therapeutic ‘Gestalt,' that is, the extent to which efficacy in combination exceeds efficacy of the constituents. Please refer to the Supplementary Materials for the references for each therapy.