Astragaloside IV reduces cerebral edema post-ischemia/reperfusion correlating the suppression of MMP-9 and AQP4.

Cerebral edema is a critical complication after intravascular thrombolysis post-acute stroke. However, clinical options remained limited for treating cerebral edema after cerebral ischemia/reperfusion (I/R) injury. In the present study, astragaloside IV, a purified extract from astragalus membranaceus, was used in the focal I/R rat model, aimed to investigate its effect on the cerebral edema. We found that astragaloside IV (10 and 20mg/kg) significantly attenuated the cerebral water content (P<0.05) and improved neurological outcomes (P<0.05) in comparison with vehicle group. Moreover, we investigate the effect of astragaloside IV on the (blood-brain barrier) BBB since cerebral edema was closely related to the permeability of the BBB. We found that the permeability of BBB was improved significantly in astragaloside IV groups compared with vehicle group via Evans blue leakage (P<0.05). This was further confirmed under the electron microscope, using lanthanum as a tracer of blood vessel permeability. Lanthanum was usually found within the blood vessel in sham group, rather than in perivascular tissues as shown in vehicle group. In drug groups, lanthanum stain was mainly restricted within the cerebral capillary, indicating the potential BBB-protective effect of astragaloside IV. Furthermore, we found that expressions of Matrix metalloproteinase-9 (MMP-9) and aquaporin 4 (AQP4) were increased in vehicle group, which were related to cerebral vasogenic edema or cytotoxic edema. The up-regulations of MMP-9 and AQP4 were inhibited significantly by astragaloside IV administration. We propose that the anti-edema potential of astragaloside IV was correlated with its regulation of MMP-9 and AQP4.

Intraarterial thrombolysis and stent placement for acute basilar artery occlusion.

PURPOSE: To study retrospectively the prognostic factors for acute basilar artery occlusion treated with intraarterial thrombolysis and stent placement. MATERIALS AND METHODS: Within 3-48 hours of disease onset, 52 patients with basilar artery occlusion were treated with emergency intraarterial thrombolysis with recombinant tissue plasminogen activator (rtPA) or urokinase (UK) or intraarterial thrombolysis combined with stent placement. Sixteen patients simultaneously received stent placement for the partial recanalization of basilar artery occlusion after intraarterial thrombolysis. The National Institutes of Health Stroke Scale (NIHSS) scores and the modified Rankin Scale (mRS) scores of the patients were estimated. RESULTS: A favorable clinical outcome occurred in 22 patients (42.3%), and 20 patients (38.5%) died. The survival rate was 61.5% (32 patients). Successful recanalization of basilar artery occlusion was achieved in 24 patients (46.2%), and partial recanalization was achieved in 16 patients (30.7%). The rate of recanalization was 76.9%. NIHSS scores less than 14, treatment time window less than 24 hours, and a good recanalization were markedly correlated with good clinical prognosis. NIHSS scores less than 14 and treatment time window less than 24 hours were significantly correlated with recanalization. NIHSS scores less than 14 and good recanalization could act as independent predictors for clinical prognosis. CONCLUSIONS: NIHSS scores less than 14 on admission and successful recanalization can predict favorable outcome for patients with basilar artery occlusion. This study shows that intraarterial thrombolysis and stent placement may be a useful treatment for acute basilar artery occlusion.

Astragaloside IV attenuates cerebral ischemia-reperfusion-induced increase in permeability of the blood-brain barrier in rats.

Astragalus membranaceus is widely used to treat stroke and chronic debilitating diseases in China, but the mechanism has not been fully demonstrated to data. In the present study, we, using astragaloside IV, a purified extract from astragalus membranaceus, to a focal cerebral ischemia/reperfusion rat model, aimed to investigate the effect of astragaloside IV on the permeability of the blood-brain barrier since disruption of blood-brain barrier induced by ischemia/reperfusion leads to serious brain injuries. We found that astragaloside IV (10, 20 mg/kg) significantly attenuated the permeability of blood-brain barrier in comparison with vehicle group after ischemia/reperfusion assessed via Evans blue leakage (P<0.05). This was further confirmed by examination of blood-brain barrier permeability under the electron microscope, using lanthanum as a tracer of blood vessel permeability. Lanthanum was usually found within the blood vessel in sham group, rather than in perivascular tissues as shown in vehicle group. In drug groups, lanthanum stain was mainly restricted within the cerebral capillary, indicating the potential protective effect of astragaloside IV on the integrity of blood-brain barrier in ischemia/reperfusion rats. Furthermore, we found that expression of occludin and zonae occludens-1 (ZO-1), the tight junction proteins, was decreased in endothelial cells in vehicle group, which, however, could be reversed by astragaloside IV administration. We propose that regulation of tight junctional proteins in the endothelial cells may be one mechanism astragaloside IV-mediated in attribution to blood-brain barrier protection in the ischemia/reperfusion rats.