Table 2.
Compiled Data of Outcomes Including Cord Edema/Inflammation, Neuronal Sprouting, Cystic Cavitation, and Apoptosis Comparing Intervention to Control.
| Study | Outcomes Measured | Results—Control | Results—NSAIDs | Significance Level |
|---|---|---|---|---|
| Cord edema/inflammation | ||||
| Campolo et al40,a | Total myeloperoxidase activity | 300 mU/g | Nap: 250 mU/g, ATB-346: 125 mU/g | P < .05 with nap compared to control and P < .05 for ATB-346 compared to nap |
| TNF-α levels | 100 mU/g | Nap: 70 mU/g, ATB-346: 50 mU/g | P < .05 when nap compared to control and ATB-346 compared to nap | |
| Histological damage score based on number of eosinophilic neurons. 1 = 1-5 neurons, 2 = 5-10 neurons, 3 = >10, 1 = <1/3 of gray matter, 5 = 1/3-1/2 of gray matter, 6 = >1/2 of gray matter | 5 | Nap: 3, ATB-346: 1 | P < .05 when nap compared to control; P < .05 when ATB-346 compared to nap | |
| Hakan el al30,a | Myeloperoxidase activity (U/g) | No SCI: 3.8 U/g SCI control: 6.5 |
Mel: 4.0 | P < .001 with mel compared to saline |
| Guth et al32 | Total lesion size measuring edema 21 days after injury (mm2) | Control: 1.62 ± 0.11 LPS: 1.63 ± 0.14 Preg: 1.84 ± 0.1 DHEA: 1.68 ± 0.12 |
Ind: 1.63 LPS and ind: 1.63 ± 0.13 Preg, LPS, and ind: 1.14 ± 0.14 DHEA, LPS, and ind: 1.12 ± 0.08 |
P < .01 for preg, LPS, and ind P < .01 for DHEA, LPS and ind |
| Experiment rerun with larger sample sizes measuring edema (mm2) | Control: 1.89 ± 0.12 Preg and LPS: 1.77 ± 0.14 |
Preg, LPS, and ind: 1.33 ± 0.14 | P < .05 for preg, LPS, and ind compared to control | |
| Simpson et al34 | SCI evaluation based on scale of mild (1) to marked (4) as determined by the authors | 2.4 ± 0.5 | SCI-nifedipine: 2.1 ± 0.6 SCI-indomethacin: 0.8 ± 0.3 |
Unknown |
| Sharma et al13 | Spinal cord water content (%) using microscope for evaluation rostral to SCI | Non-SCI control: 71.56 ± 0.42 SCI control: 74.48 ± 0.38 |
SCI with 1 mg ind: 74.76 ± 0.53 | P > .05 |
| SCI with 5 mg ind: 74.68 ± 0.88 | P > .05 | |||
| SCI with 10 mg ind: 72.74 ± 0.32 | P < .05 | |||
| Spinal cord water content (%) using microscope for evaluation caudal to SCI | Non-SCI control: 71.38 ± 0.42 SCI control: 75.34 ± 0.42 |
SCI with 1 mg ind: 75.78 ± 0.63 | P > .05 | |
| SCI with 5 mg ind: 74.89 ± 0.61 | P > .05 | |||
| SCI with 10 mg ind: 72.64 ± 0.38 | P < .05 | |||
| Spinal cord water content (%) using microscope for evaluation of total spinal cord injury | Non-SCI control: 72.03 ± 0.38 SCI control:76.58 ± 0.34 |
SCI with 1 mg ind: 76.84 ± 0.76 | P > .05 | |
| SCI with 5 mg ind: 77.23 ± 0.67 | P > .05 | |||
| SCI with 10 mg ind: 74.48 ± 0.52 | P < .05 | |||
| Winkler et al51 | Water content in spinal cord (%) | Non-SCI control: 72.03 | SCI treated with ind: 73.31 | P < .05 with ind compared to control |
| SCI control: 76.23 | ||||
| Sharma et al14 | Water content of spinal cord (%) | Non-SCI control group (%): 67.64 ± 0.23 | Non-SCI group treated with 5 mg/kg ind: 66.58 ± 0.32 Non-SCI with 10 mg/kg ind: 66.74 ± 0.38 |
N/A |
| Control SCI: 70.18 ± 0.34 | 5 mg/kg ind with SCI: 69.43 ± 0.33 | P < .01 | ||
| Control SCI: 70.18 ± 0.34 | 10 mg/kg ind with SCI: 68.28 ± 0.18 | P < .01 | ||
| Hains et al33 | Inflammation evaluated by PGE2 immunohistochemistry at 12 hours postinjury | 6389 ± 784 | Staining intensity for NS-398: 2331 ± 1177 | P < .05 |
| Neuronal sprouting/myelination | ||||
| Wang et al36,a | Central horn 5-HT fiber length in complete transection model at 5 weeks (µm) | 0 | Ibu at 35 mg: 5, Ibu at 70 mg: 11 | P < .05 ibu; regeneration seen across transection in ibu group |
| Contusion model fiber length at 2 weeks (µm) | 75 | Nap: 100, ibu: 90 | P > .05 for nap and ibu | |
| Contusion model fiber length at 6 weeks (µm) | 50 | Nap: 4, ibu: 200 | P < .01 for ibu group | |
| Optical density of BDA-labeled CST fibers rostral to injury | 0.12 | Ibu: 0.7 | P < .05 for ibu group | |
| Sharp et al35,a | Axonal sprouting | 27 axons per high-powered section | Ibu: 25 axons per high-powered section | P > .05 |
| Xing et al37,a | Total oligodentrocytes 6-10 mm rostral to lesion 5 days after SCI injury | 1600 | Ibu: 1800, ind: 1800, nap: 1600 | P < .05 for ibu and ind |
| Total oligodentrocytes 6-10 mm caudal to lesion 5 days after SCI injury | 1500 | Ind: 2000, ibu: 1950, nap: 1450 | P < .05 for ibu and ind | |
| MBP-labeled myelin 3-4 mm caudal to lesion 6 weeks after SCI (units measured as arbitrary units) | 36 | Nap: 40, ibu: 100, ind 50 | Ibu P < .05; qualitatively increased myelination for ind and ibu groups seen on electron microscopy | |
| 3-4 mm caudal with Luxol fast blue stained myelin (units measured as arbitrary units) | 25 | Nap: 22, ibu: 100, ind: 75 | P < .01 for ibu and ind | |
| 3-4 mm rostral with MBP-labeled myelin (units measured as arbitrary units) | 42 | Nap: 38, ind: 75, ibu: 100 | P < .05 ibu; qualitatively increased myelination for ind and ibu groups seen on electron microscopy | |
| 3-4 mm rostral with LFB (units measured as arbitrary units) | 45 | Nap: 10, ind: 50, ibu: 105 | P < .05 for ibu group | |
| Fu et al31,a | CST sprouts/rat in dorsal over hemi-section rats 1 hour postinjury | 5 sprouts | Nap: 1, ibu: 31 | P < .05 for ibu group |
| CST axons/slide 7-10 mm distal to injury | 4 | Nap: 3, ibu: 9 | P < .05 for ibu group | |
| 5HT fiber length (mm) | 8 | Nap: 10, ibu: 17 | P < .01 for ibu group | |
| Serotonin fiber length (µm) | 13 | Ibu: 23 | P < .05 | |
| # CST fiber >200 µm 1-2 mm from SCI in gray matter and at 3-4 mm, 5-6 mm, 7-8 mm, and 9-10 mm | 0, 5, 5, 3, 0 | 15, 30, 31, 29, 25 | P < .05 | |
| Gray and white matter CST fibers/rat found at least 1 mm distal to lesion | 25 | 200 | P < .05 | |
| Cystic cavitation | ||||
| Pedram et al38 | Measured based on Rexel classification: 0 = normal with no vacuolization, 1 = mild with <10% cells injured, 2 = moderate 10-50%, 3 = severe with >50% | Ventral horn gray matter: 0 | Ventral horn gray matter for mel: 0 | P > .05 |
| Intermediate gray matter: 0.5 ± 0.57 | Intermediate gray matter: 0 | P > .05 | ||
| Dorsal horn gray matter: 0 | Dorsal horn gray matter: 0 | P > .05 | ||
| Wang et al36,a | Spared tissue 2 weeks after injury (µm) | 300 | Nap: 300, ibu: 550 | P < .05 for ibu group compared to control/nap and nap, P > .05 compared to control |
| Spared tissue 6 weeks after injury (µm) | 250 | Nap: 250, ibu: 450 | P < .05 for ibu group compared to control/nap and nap, P > .05 compared to control | |
| Redondo-Castro and Navarro39,a | Total amount of spared tissue in epicenter of cord injury (µm2) | 2.0 × 109 | Ibu: 1.7 × 109 | P > .05 |
| Tissue spared at periphery of lesion (µm2) | 4.0 × 109 | Ibu: 3.5 × 109 | P > .05 | |
| Myelinated tissue at different areas of the lesion (µm2) | 2 000 000 at −3000 µm from epicenter, none at epicenter | Ibu: 3 000 000 at −3000 µm | P < .05 ibu versus control | |
| Guth et al32 | Total lesion size (mm2) at 28 days | Control: 0.93 ± 0.1 LPS: 0.49 ± 0.1 |
Ind: 1.05 ± 0.128 mm2 LPS and ind: 0.11 ± 0.4 |
P < .01 for LPS P < .001 for LPS and ind |
| Total lesion size after crush injury at 28 days | Control: 0.94 ± 0.13 LPS: 0.63 ± 0.09 Preg: 1.00 ± 0.11 DHEA: 0.94 ± 0.1 |
Ind: 1.05 ± 0.13 LPS and ind: 0.49 ± 0.11 Preg, LPS, ind: 0.3 ± 0.04 DHEA, LPS, ind: 0.33 ± 0.3 |
P < .01 for preg, LPS, and ind group P > .05 for LPS and ind group P < .01 for DHEA, LPS, and ind group |
|
| Crush injury repeated with increased sample size (mm2) | Control: 0.99 ± 0.09 Preg and LPS: 0.94 ± 0.12 mm2 |
LPS and ind: 0.49 ± 0.08 mm2 | P < .01 for LPS and ind group | |
| Simpson et al34 | Total tissue loss based on author scale of mild to marked injury | Sham control: 0.0 | Sham ind: 0.0 | Unknown |
| SCI control: 1.1 ± 0.4 | SCI ind: 0.1 ± 0.1 | |||
| Hains et al33 | Total viable tissue loss (%) | 32.2 ± 2.7 | NS-398: 17.6 ± 3.21 | P < .05 |
| Apoptosis of cells | ||||
| Campolo et al40,a | TUNEL positive cells/field | 4.8 | Nap: 3 ATB-346: 1.8 |
Nap P < .001 compared to control, ATB P < .001 compared to nap |
| Densitometric data (OD m2) for antiapoptotic bcl2 | 100 | Nap: 1600 ATB-346: 3700 |
P < .001 for ATB346 compared to nap | |
| Proaopoptotic Bax units | 4600 | Nap: 1000 ATB-346: 700 |
P < .001 for nap and ATB-346 compared to control | |
| Hakan et al30,a | % DNA fragmentation | Control without SCI: 0.04 Control with SCI: 0.16 |
SCI + mel: 0.06 | P < .01 |
| Xing et al37,a | Total TUNEL (+) cells/section 6-10 mm rostral to lesion 5 days after injury | 70 | Nap: 70 Ibu: 45 Ind: 35 |
P < .01 for both ibu and ind; nearly all apoptotic cells were in white matter |
| Total TUNEL (+) cells/section 6-10 mm caudal to lesion 5 days after injury | 45 | Nap: 45 Ibu: 28 Ind: 27 |
P < .01 for both ibu and ind; nearly all apoptotic cells were in white matter | |
Abbreviations: NSAID, nonsteroidal anti-inflammatory drug; TNF-α, tumor necrosis factor-α; ind, indomethacin; ibu, ibuprofen; nap, naproxen; mel, meloxicam; preg, pregnenolone.
a Data estimated from figures in the original article.