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Object: Brain edema formation is a serious complication of ischemic stroke and can lead to mechanical compression of adjacent brain structures, cerebral herniation, and death. Furthermore, the space-occupying effect of edema impairs regional cerebral blood flow (rCBF), which is particularly important in the penumbra phase of stroke. In the present study, the authors evaluated the natural course of edema formation in the hyperacute phase of focal cerebral ischemia., Methods: Middle cerebral artery occlusion (MCAO) or a sham procedure was performed in rats within an MR imaging unit (in-bore occlusion). Both pre- and postischemic images could be compared on a pixel-by-pixel basis. The T2 relaxation time (T2RT), a marker for brain water content, was measured in regions of interest., Results: A significant increase in the T2RT was detectable as early as 20-45 minutes after MCAO. At this early time point the midline shift (MLS) amounted to 0.214 +/- 0.092 cm in the MCAO group and 0.061 +/- 0.063 cm in the sham group (p < 0.007). The T2RT and MLS increased linearly thereafter. Evans blue dye was intravenously injected in additional animals 20 and 155 minutes after MCAO. Extravasation of the dye was visible in all animals, indicating increased permeability of the blood-brain barrier., Conclusions: Vasogenic brain edema occurs much earlier than expected following permanent MCAO and leads to MLS and mechanical compression of adjacent brain structures. Since compression effects can impair rCBF, early edema formation can significantly contribute to infarct formation and thus represents a promising target for neuroprotection.

Object: In territorial stroke vasogenic edema formation leads to elevated intracranial pressure (ICP) and can cause herniation and death. Brain swelling further impairs collateral blood flow to the ischemic penumbra and causes mechanical damage to adjacent brain structures. In the present study the authors sought to quantify the impact of this space-occupying effect on ischemic lesion formation., Methods: Wistar rats were assigned to undergo bilateral craniectomy or a sham operation and then were subjected to temporary middle cerebral artery occlusion (MCAO) for 90 minutes. A clinical evaluation and 7-T MR imaging studies were performed 5 and 24 hours after MCAO. The absolute brain water content was determined at 24 hours by using the wet/dry method., Results: Bilateral craniectomy before MCAO led to a drastic reduction in lesion volume at both imaging time points (p < 0.0001). Ischemic lesion volume was 2.7- and 2.3-fold larger in sham-operated animals after 5 and 24 hours, respectively. Clinical scores were likewise better in rats that had undergone craniectomy (p < 0.05). After 24 hours the midline shift differed significantly between the 2 groups (p < 0.001), but not after 5 hours. The relation between brain water content and ischemic lesion volume as well as the T2 relaxation time within the infarcted area was not different between the groups (p > 0.05)., Conclusions: The data indicated that collateral damage caused by the space-occupying effect of a large MCA territory stroke contributes seriously to ischemic lesion formation. The elimination of increased ICP thus must be regarded as a highly neuroprotective measure, rather than only a life-saving procedure to prevent cerebral herniation. Further clinical trials should reveal the neuroprotective potential of surgical and pharmacological ICP-lowering therapeutic approaches.