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-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 x 0.5, 4 x 1, or 4 x 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 x 0.5 mg/kg) in the hippocampus (-53%, p = 0.07) and the parietal cortex (-39%, ns). At 0.5 + 4 x 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 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 neurological deficit evaluated with a 9-point scale was also improved with enoxaparin at 0.5 + 4 x 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 x 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.
Wahl
F
F
Aventis Pharma, CNS Research, Ischemia-Trauma Department, Vitry-sur-Seine, France. florence.wahl@aventis.com
Grosjean-Piot
O
O
Bareyre
F
F
Uzan
A
A
Stutzmann
J M
JM
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D017984:Enoxaparin / Q000627:therapeutic use*; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D009422:Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000925:Anticoagulants; D017984:Enoxaparin