Pentoxifylline effect on functional, biochemical and histological ratings after experimental spinal cord impact

Introduction: Pentoxifylline (PTX) may increase blood flow, cellular derformability, and decrease platelet aggregation, inflammation and secondary damage after acute spinal cord injury. This study examines the effects of two PTX treatment protocols on functional, biochemical, and histological recovery after acute spinal cord impact injury in an anesthetized rat model. Methods: 60 Hooded Long-Evans pentobarbital anesthetized rats were injured by standardized 10g×25mm weight-drop method onto exposed spinal cord (T10). Treatment was randomized, blinded and given in equal diluent volumes at 5, 30, and 60 min after impact: Group I: Saline; Group II: PTX 10 mg/kg, 5 mg/kg, 5 mg/kg; and Group III: PTX 25 mg/kg, 15 mg/kg, 15 mg/kg. Blinded to group, 3 scales (BBB¹, Tarlov², Rivlin-Tator Angleboard³) were serially applied to assess motor function for 28 days. At autopsy, spinal cord segments above, at and below impact site were analyzed for biochemical markers of injury (serotonin to metabolite ratio) and by 3 histologic scales (qualitative, lesion size, and myelin density). Analysis was by ANOVA and RM-ANOVA, with appropriate after testing. Results: At baseline, the 3 groups were equivalent. At 30 and 60 min after impact injury and blinded treatment, group I had significantly higher mean HR and BP than both PTX groups (p<.02). All groups showed improvement in motor function over 28 days (p<.01), with no significant differences among groups (p>.05). Biochemical analysis showed the highest serotomn and metabolite levels at the impact site, with no significant serotonin/metabolite ratio difference among groups (p>.05). Histological evaluation confirmed comparable injury at impact sites, with proximal sections least affected for all groups (p<.05). Further qualitative assessment blinded to group showed significant changes in histology above vs below impact site in Group I control rats, but not in Group II or III PTX treated rats. Conclusions: Subtle but significant patterns of medication treatment effect can be reliably tracked by these functional, biochemical, and histological outcome measures in this rat model of acute spinal cord impact injury. Lack of dramatic functional or biochemical correlates of histologie improvement suggest that alternative PTX dose or treatment duration may be required if PTX post-injury treatment is to be effective.