Tehran University Medical Journal

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Background: Ultrasound (US) has been used in neuroprotection after cerebral ischemia however, its use is controversial. Application of US in combination with fibrinolytic agents may improve fibrinolytic effects. In this study the effects of US, alone or in combination with tissue plasminogen activator (tPA), on brain ischemic injury were examined and we studied whether US is protective in the brain injured by ischemia under normothermic conditions.
Methods: We performed two studies. In the first study, rectal and brain temperatures were compared. In the second study, we studied whether US alone or in combination with tPA is neuroprotective in thromboembolic stroke. To induce focal cerebral ischemia, a clot was formed in a catheter. Once the clot had formed, the catheter was advanced 17 mm in the internal carotid artery until its tip was 1-2 mm away from the origin of the middle cerebral artery (MCA). The preformed clot in the catheter was then injected, and the catheter was removed. The wound was then closed and the infarction volume, edema and neurological deficits were measured after MCA occlusion.
Results: The temperature in the brain was approximately 0.50 ºC lower than the rectal temperature. In the control, US+low tPA, low tPA, US+high tPA and, high tPA groups, the infarct volume (%) was 34.56±4.16, 17.09±6.72, 21.25±7.8, 13.5±10.72 and 20.61±6.17 (mean ±SD) at 48 h after MCA occlusion, respectively. The results indicate that US alone reduces the infarct volume by 30% compared to that of the control group (P<0.05). US improved neurological deficits and reduced brain edema significantly (p<0.05).
Conclusions: This study indicate that US appears to have a protective effect, alone and in combination with tPA, in an embolic model of stroke.

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Background: Ultrasound (US) has been used in neuroprotection after cerebral ischemia, however the mechanism of action remains unclearly. We have previously shown the protective effect of ultrasound on infarction volume and brain edema in ischemic brain injured at normothermic condition. Ultrasound may also amplify the effect of fibrinolytic medications in thrombolysis process .We have also shown that hyperthermia can exacerbate cerebral ischemic injury and that the efficacy of tissue plasminogen activator (tPA) is reduced in the presence of hyperthermia. In this study, the effects of US alone or in combination with tPA on brain ischemic injury were evaluated.

Methods: Focal ischemic brain injury was induced by emblazing a pre-formed clot into the middle cerebral artery in rats. Principally, we examined whether US can reduce the perfusion deficits and, the damage of blood- brain barrier (BBB) in the ischemic injured brain. There are two series of experiments at this study .in the first series, animals were randomly assigned to four groups (n=7 per group) as follows: 1-control (saline), 2-US (1W/cm², 10 duty cycle ), 3- US+high- tPA (1W/cm², 10 duty cycle +20 mg/kg) and 4- high -tPA (20 mg/kg). We also examined the effects of US and tPA on BBB integrity after ischemic injury. The animals were assigned into four groups (n=7 per group), treatment is the same as above. BBB permeability was assessed by the Evans blue (EB) extravasations method at 8 h after MCA occlusion. BBB permeability was evaluated by fluorescent detection of extravagated Evans blue dye and Perfusion deficits were analyzed using an Evans blue staining procedure. The perfused microvessels in the brain were visualized using fluorescent microscopy. Areas of perfusion deficits in the brain were traced, calculated and expressed in mm².

Results: The results showed that US improved neurological deficits significantly (p<0.05). The administration of US significantly decreased perfusion deficits and BBB permeability. In the control set, for the US+high tPA, high tPA only and US only groups, the mean perfusion deficits (±SD) were 14.32±3.15, 7.03±4.08, 5.92±1.90 and 9.14±3.37 mm², respectively, 8 h after MCA occlusion (P<0.05).

Conclusions: These studies suggest that US is protective in a rat embolic model of stroke due to decreased perfusion deficits.