The data demonstrated that hypothermia was effective in attenuating BBB disruption by hyperosmolar mannitol during isoflurane as well as pentobarbital anesthesia. The degree of disruption appeared smaller during isoflurane than during pentobarbital anesthesia in both the normothermic as well as the hypothermic groups.

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Abstract—Activation of the mammalian target of rapamycin (mTOR) leads to cell growth and survival. We tested the hypothesis that inhibition of mTOR would increase infarct size and decrease microregional O2 supply/consumption balance after cerebral ischemia–reperfusion. This was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1 h and reperfusion for 2 h with and without rapamycin (20 mg/kg once daily for two days prior to ischemia). Regional cerebral blood flow was determined using a C14-iodoantipyrine autoradiographic technique. Regional small-vessel arterial and venous oxygen saturations were determined microspectrophotometrically. The control ischemic-reperfused cortex had a similar blood flow and O2 consumption to the contralateral cortex. However, microregional O2 supply/consumption balance was significantly reduced in the ischemic-reperfused cortex. Rapamycin significantly increased cerebral O2 consumption and further reduced O2 supply/consumption balance in the reperfused area. This was associated with an increased cortical infarct size (13.5 ± 0.8% control vs. 21.5 ± 0.9% rapamycin). We also found that ischemia–reperfusion increased AKT and S6K1 phosphorylation, while rapamycin decreased this phosphorylation in both the control and ischemic-reperfused cortex. This suggests that mTOR is important for not only cell survival, but also for the control of oxygen balance after cerebral ischemia–reperfusion.

Our data suggest that even in the early stage of focal cerebral ischemia, the degree of BBB disruption in response to the exogenous VEGF is much greater in the ischemic than in the non-IC and that the mechanism of the increase of BBB disruption by VEGF in the IC involves the NOS pathway.

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To determine whether blockade of ionotropic glutamate receptors such as NMDA or AMPA receptors would attenuate blood-brain barrier (BBB) disruption in focal cerebral ischemia, 15 min before middle cerebral artery (MCA) occlusion, CGS-19755 or NBQX was injected intraperitoneally in rats. At 1 h after MCA occlusion, BBB permeability was determined by measuring the transfer coefficient (K(i)) of (14)C-α-aminoisobutyric acid and the volume of dextran distribution. With MCA occlusion, K(i) was increased in the ischemic cortex (IC) (316%). CGS-19755 attenuated the increase in K(i) in the IC (-46%), but NBQX did not significantly decrease it. The difference in the volume of dextran distribution between the IC and the contralateral cortex became insignificant with the blockade of NMDA or AMPA receptors. Our data demonstrated that blockade of NMDA or AMPA receptors could attenuate the BBB disruption in focal cerebral ischemia and suggest that ionotropic glutamate receptors are involved in part in BBB disruption.

Background and Purpose-After cerebral vessel blockage, local blood flow and O 2 consumption becomes lower and oxygen extraction increases. With reperfusion, blood flow is partially restored. We examined the effects of ischemia-reperfusion on the heterogeneity of local venous oxygen saturation in rats in order to determine the pattern of microregional O 2 supply/consumption balance in reperfusion. Methods-The middle cerebral artery was blocked for 1 hour using the internal carotid approach in 1 group (n=9) and was then reperfused for 2 hours in another group (n=9) of isoflurane-anesthetized rats. Regional cerebral blood flow was determined using a C 14 -iodoantipyrine autoradiographic technique. Regional small vessel arterial and venous oxygen saturations were determined microspectrophotometrically. Results-After 1 hour of ischemia, local cerebral blood flow (92±10 versus 50±10 mL/min per 100 g) and O 2 consumption (4.5±0.6 versus 2.7±0.5 mL O 2 /min per 100 g) decreased compared with the contralateral cortex. Oxygen extraction increased (4.7±0.2 versus 5.4±0.3 mL O 2 /100 mL) and the variation in small vein (20-60 μm) O 2 saturation as determined by its coefficient of variation (=100×SD/mean) increased (5.5 versus 10.5). With 2 hours of reperfusion, the blood flow decrement was reduced and O 2 consumption returned to the value in the contralateral cortex. Oxygen extraction remained elevated in the ischemic-reperfused area and the coefficient of variation of small vein O 2 saturation increased further (17.3). Conclusions-These