Background and Purpose-To study whether intravascular or hemodynamic factors contribute to the marked neuroprotective effect of albumin therapy in focal cerebral ischemia, 2 complementary methods were applied: laser-scanning confocal microscopy (LSCM) and laser-Doppler perfusion imaging (LDPI). Methods-In the LSCM study, Sprague-Dawley rats were anesthetized with halothane/nitrous oxide, and a cranial window was placed over the dorsolateral frontoparietal cortex. Rats received 2-hour middle cerebral artery occlusion (MCAO) by an intraluminal suture and were treated with human albumin (1.25 g/kg; nϭ4) or saline (nϭ3) after 30 minutes of recirculation. Video images of cortical vessels were continually acquired and were digitized offline to measure diameters and fluorescent erythrocyte velocities. In the LDPI study, cortical perfusion was measured in anesthetized SpragueDawley rats that received 2-hour MCAO and were treated with albumin (2.5 g/kg; nϭ6) or saline (nϭ5) at 30 minutes after recirculation. Results-In the LSCM study, MCAO was associated with arteriolar dilation and slowing of capillary and venular erythrocyte perfusion. During the first 15 to 30 minutes of postischemic recirculation, prominent foci of vascular stagnation developed within cortical venules, associated with thrombuslike foci and adherent corpuscular structures consistent in size with neutrophils. Saline administration failed to affect these phenomena, while albumin therapy was followed by significant increases in arteriolar diameter (Ϸ12%; Pϭ0.007) and by a prompt improvement of venular and capillary erythrocyte perfusion and a partial disappearance of adherent thrombotic material. Albumin therapy increased erythrocyte flow velocity in both capillaries (288Ϯ73% versus 76Ϯ18% in the saline group; Pϭ0.023) and venules (2.7-fold [Pϭ0.001] versus 1.0-fold in the saline group [PϭNS]). In the LDPI study, cortical perfusion declined during MCAO and rose initially with recirculation (to Ϸ135% of baseline) in both groups. Mean cortical perfusion improved slightly (Ϸ14%; PϭNS) in albumin-treated animals. Conclusions-These results reveal a beneficial effect of albumin therapy in reversing stagnation, thrombosis, and corpuscular adherence within cortical venules in the reperfusion phase after focal ischemia and support its utility in the treatment of acute ischemic stroke.

Background and Purpose-A major limitation of intracerebral hemorrhage (ICH) research is the lack of reproducible animal models. The present study was conducted to validate in the mouse the double-injection method of ICH initially developed in the rat. We investigated the effect of intrastriatal injection of blood or cerebrospinal fluid (CSF) on cerebral blood flow (CBF), neurological score, hematoma volume, and brain swelling. Methods-Male C57BL/6 mice were anesthetized with halothane/nitrous oxide delivered by face mask. Rectal and cranial temperatures were regulated at 37°C to 37.5°C. Mice were placed in a stereotactic frame, and a 30-gauge stainless steel cannula was introduced through a burr hole into the left striatum. Each mouse received a 5-L injection of either whole blood or CSF (over 3 minutes), followed 7 minutes later by 10 L injected over 5 minutes. The injection cannula was slowly withdrawn 10 minutes after the second injection. Control mice had only cannula insertion. CBF was studied by laser Doppler perfusion imaging. Neurological status was evaluated on days 1 and 2. After 2 days, hematoma volume and brain swelling were calculated. Results-Physiological values were stable. Mice with ICH but not those with CSF or cannula alone had a marked, persistent neurological deficit and a highly reproducible hematoma, whose meanϮSEM volume was 2.0Ϯ0.2 mm

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