Enoxaparin Improves Outcomes in Cerebral Infarction Rats by Reducing Microcirculatory Thrombosis and Hypoperfusion

Abstract

Microcirculatory disturbances may play an important role in futile recanalization. This study investigated the early factors affecting the prognosis of cerebral infarction in rats and whether low-molecular-weight heparin improves microcirculation disorders. We used a male rat middle cerebral artery occlusion (MCAO) model with 90 min transient MCAO (tMCAO) or permanent MCAO (pMCAO) ischemia, and analyzed after 24 h. Cortical blood flow was monitored using laser speckle blood flow imaging. Furthermore, 1.5 mg/kg Enoxaparin (Enox) was administered 30 min before ischemia or 1 h post-reperfusion. The tMCAO group received saline. Our results showed that the proportion of moderate and severe (M&S) injuries was 54.2% in tMCAO rats, 100% in pMCAO rats, and reduced to 25% in the enoxaparin pre-ischemic (Enox-pre) group. The reperfusion rats had persistent hypoperfusion and the lowest blood flow after 1 h post-reperfusion. The 1 and 24 h post-reperfusion cortical blood flow was negatively correlated with infarct volume and neurological scores. The Enox-pre group had higher blood flow than the tMCAO group at 1 h post-reperfusion (p < 0.05). Enox-pre reduced fibrin deposition after 1 h post-reperfusion (p < 0.01), improved microvascular patency after 1 and 24 h (p < 0.01), and decreased Evans blue leakage after 24 h (p < 0.001). We concluded that 50% of the futile recanalization rate also exists in rats with recanalization 1.5 h post-infarction. The degree of reperfusion blood flow recovery significantly affects cerebral infarction outcomes. Enox-pre reduces the proportion of poor outcomes by reducing early microthrombus formation, enhancing microcirculation, increasing reperfusion blood flow, and mitigating blood–brain barrier (BBB) disruption.