Enoxaparin reduces brain edema, cerebral lesions, and improves motor and cognitive impairments induced by a traumatic brain injury in rats

Traumatic brain injury (TBI) is often accompanied by secondary ischemia due , in part, to edema-induced blood vessel compression. Enoxaparin, a low-mol ecular weight heparin, which is efficacious in models of myocardial and bra in ischemia was studied in lateral fluid percussion-induced TBI in rats. En oxaparin was administered 2 h post-TBI at 0.5 mg/kg i.v. followed by 4 x 0. 5, 4 x 1, or 4 x 2 mg/kg s.c. over 30 fi. Brain edema was measured in the h ippocampus, temporal cortex and parietal cortex. Edema was reduced by enoxa parin (0.5 + 4 x 0.5 mg/kg) in the hippocampus (-53%, p = 0.07) and the par ietal cortex (-39%, ns). At 0.5 + 4 x 1 mg/kg edema was reduced in the hipp ocampus (-63%, p < 0.05) and the parietal cortex (-47%, p = 0.06). At 0.5 4 x 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 x 1 mg/kg (-50%,p < 0.05), and at 0.5 + 4 x 2 mg/kg (-35%, ns). The neuro logical deficit evaluated with a 9-point scale was also improved with enoxa parin at 0.5 + 4 x 1 mg/kg 1 week post-TBI (p < 0.05). The cognitive impair ment evaluated with a Lashley maze task was improved with enoxaparin (0.5 4 x 1 mg/kg) from 48 h (p < 0.05) to 2 weeks post-TBI (p < 0.01). Our resu lts demonstrate for the first time that enoxaparin significantly reduces th e brain contusion and edema, and improves the functional outcomes induced b y a TBI. Therefore, enoxaparin could be a candidate drug to treat acute bra in-injured patients.