Enoxaparin Reduces Brain Edema, Cerebral Lesions, and Improves Motor and Cognitive Impairments Induced by a Traumatic Brain Injury in Rats

Authors:
  • OGOdile Grosjean-Piot
    Odile Grosjean-Piot
  • FBFlorence Bareyre
    Florence Bareyre
  • AUAndré Uzan
    André Uzan
  • JSJean-Marie Stutzmann
    Jean-Marie Stutzmann
Publisher website
Google Scholar
Abstract
Traumatic brain injury (TBI) is often accompanied by secondary ischemia due, in part, to edema-induced blood vessel compression. Enoxaparin, a low-molecular weight heparin, which is efficacious in models of myocardial and brain ischemia was studied in lateral fluid percussion–induced TBI in rats. Enoxaparin was administered 2 h post-TBI at 0.5 mg/kg i.v. followed by 4 × 0.5, 4 × 1, or 4 × 2 mg/kg s.c. over 30 h. Brain edema was measured in the hippocampus, temporal cortex and parietal cortex. Edema was reduced by enoxaparin (0.5 + 4 × 0.5 mg/kg) in the hippocampus (−53%, p = 0.07) and the parietal cortex (−39%, ns). At 0.5 + 4 × 1 mg/kg edema was reduced in the hippocampus (−63%, p < 0.05) and the parietal cortex (−47%, p = 0.06). At 0.5 + 4 × 2 mg/kg, the reduction was more important in the hippocampus (−69%, p < 0.01) and in the parietal cortex (−50%, p < 0.05). No reduction was seen in the temporal cortex. The lesion size was reduced by enoxaparin at 0.5 + 4 × 1 mg/kg (−50%, p < 0.05), and at 0.5 + 4 × 2 mg/kg (−35%, ns). The neurological deficit evaluated with a 9-point scale was also improved with enoxaparin at 0.5 + 4 × 1 mg/kg 1 week post-TBI ( p < 0.05). The cognitive impairment evaluated with a Lashley maze task was improved with enoxaparin (0.5 + 4 × 1 mg/kg) from 48 h ( p < 0.05) to 2 weeks post-TBI ( p < 0.01). Our results demonstrate for the first time that enoxaparin significantly reduces the brain contusion and edema, and improves the functional outcomes induced by a TBI. Therefore, enoxaparin could be a candidate drug to treat acute brain-injured patients.

This publication has 40 references indexed in Scilit: