Enoxaparin in experimental stroke - Neuroprotection and therapeutic windowof opportunity

Background and Purpose-Heparin and heparinoids have long been proposed for stroke treatment. This study investigates the effect of enoxaparin (Lovenox , Clexane), a low-molecular-weight heparin, on functional outcome (neurosco re) and lesion size in stroke models with reversible and irreversible cereb ral ischemia using middle cerebral artery occlusion (MCAO) in the rat, Methods-Ischemia was induced in rats by transient occlusion for 2 hours or by permanent electrocoagulation of the left MCA. Forty-eight hours after is chemia, neurological deficit was evaluated by scoring sensorimotor function s and ischemic damage was quantified by histological evaluation of lesion v olumes. Results-After transient MCAO, enoxaparin at 2x1.5 mg/kg IV (2 and 24 hours after insult) significantly reduced lesion size by 30% (P<0.05) and improve d neuroscore (P<0.01). This significant effect on lesion size and neuroscor e was still evident when treatment was started 5 hours after insult. Admini stered under the same protocol with a 5 hours delay post permanent MCAO, en oxaparin reduced lesion size by 49% (P<0.05) and improved neuroscore (P<0.0 1). Conclusions-This study indicates that standard nonhemorrhagic doses of enox aparin reduce ischemic damage with a wide therapeutic window. In addition t o its anticoagulant properties, other properties of enoxaparin could act in synergy to explain its neuroprotective profile in ischemia. Thus clinical application of enoxaparin treatment in stroke warrants serious consideratio n.