Effect of co-ultraPEALut treatment on histological alterations of the spinal cord tissue 24 hours after injury. Spinal cord samples were collected from the perilesional area 24 hours after injury and stained with H&E. Significant damage to the spinal cord was assessed in SCI-operated mice stained with H&E (a, histological score e) compared with sham-operated mice (data not shown). Low protection from SCI was observed in the tissue collected from mice treated with PEA at the dose of 1 mg/kg (b, histological score e), while a strong and important protection on the severity of trauma was observed following treatment with the co-ultramicronized composite co-ultraPEALut at the dose of 1 mg/kg (d, histological score e). Indeed, the treatment of PEA + Lut association (administered as combination therapy) was not able to protect the tissue damage induced by SCI (c, histological score e). The histological score was made by an independent observer. Values expressed as mean ± SEM of ten mice for each group. *P <0.001 versus sham; °P <0.01 versus SCI. Moreover, the degree of motor disturbance was assessed every day until 10 days after SCI by Basso Mouse Scale (BMS) open-field score. Treatment with the co-ultraPEALut at the dose of 1 mg/kg reduced the motor disturbance after SCI more effectively than the treatment with PEA and Lut administered alone (f), or with the pretreatment of the association of PEA + Lut administered as combination therapy, (f). This figure is representative of at least three experiments performed on different experimental days. Values expressed as mean ± SEM of ten mice for each group. *P <0.01 versus sham; °P <0.01 versus SCI. BMS, Basso Mouse Scale; H&E, hematoxylin and eosin; Lut, luteolin; ND, not detectable; SCI, spinal cord injury; SEM, standard error of the mean; PEA, palmitoylethanolamide.