The Effect of Mechanical Control of Brain Blood Flow on the Embolic Model of Stroke after Delayed Tissue Plasminogen Activator Therapy

Stroke is a major cause of mortality and long term disability in adults. It has been reported that the mechanical flow control (MFC) of brain reduces reperfusion injury. Therefore, in the present study the effect of MFC on embolic stroke model after delayed tissue Plasminogen Activator (tPA) therapy in ovariectomized-female rat was investigated.

In this experimental study thirty-two female rats (200 to 250 g) were divided into four groups as following: Control (ovariectomized and stroke induction), MFC (ovariectomized, stroke induction and occluded and released common carotid arteries), tPA (ovariectomized, stroke induction and tPA injection) and tPA+MFC (ovariectomized, stroke induction, tPA injection and occluded and released common carotid arteries). All animals were ovariectomized and one month later, stroke was induced by a natural clot injection into the right middle cerebral artery. tPA (0.9 mg/kg i.v) was administered at 6 h and MFC was induced at 6.5 h after the stroke by 5 cycles of occluding (30 sec) and releasing (30 sec) common carotid arteries. Infarct volume and neurological deficits were measured two days later and then compared.

Compared to the control group (32±1.6%), tPA (43±5.2%) increased the infarct volume (p<0.05) while combination of tPA+MFC (17±5%) significantly reduced it (p<0.001). Although tPA increased blood brain flow (p<0.001) and neurological deficits (p<0.05), application of MFC at 30 min after tPA administration, reduced both of them (p<0.001and p<0.05, respectively).

Based on our findings, late tPA therapy followed by application of MFC shows neuroprotective effects.