In Vivo Microvascular Analysis of Albumin Therapy in Focal Cerebral Ischemia: Dynamic Laser Confocal Microscopy.
To study whether hemodynamic alterations are responsible for the marked neuroprotective effect of albumin in focal ischemia, we used a newly developed method for studying brain microcirculation, combining in vivo fluorescence microscopy of labeled erythrocytes and plasma with confocal microscopy. Sprague-Dawley (SD) rats were anesthetized with halothane/nitrous oxide, and a cranial window was placed in the dorsolateral frontoparietal cortex. Cortical direct current (DC) potential was also recorded. Rats received 2h middle cerebral artery occlusion (MCAo) by intraluminal suture coated with poly-L-Lysine and were treated with human albumin (Alb, n=4, 1.25g/kg) or saline (Sal, n=3) following 30 min of recirculation. Video images of cortical vessels were continually acquired and were digitized off-line to measure diameters and flow velocities. In separate experiments, anesthetized SD rats received 2h MCAo and were treated with Alb (2.5g/kg; n=6),) or Sal (n=5) 15 min after recirculation. Laser Doppler Perfusion Imaging (LDPI) was measured. MCAo was associated with arteriolar dilatation and slowing of capillary and venular perfusion together with recurrent DC depolarizations. During the first 15–30 min of postischemic recirculation, prominent foci of vascular stasis developed within cortical venules, associated with thrombus-like stagnant foci and adherent intra-venular corpuscular structures. Sal administration failed to affect these phenomena, while Alb therapy was followed in many cases by improvement of venular flow and disappearance of adherent corpuscules and thrombotic material. In the LDPI study, CBF declined during MCAo and rose initially with recirculation (to 130%) identically in Alb and Sal rats. Alb led to an additional sustained CBF increase of 17% (p<.0001), but Sal caused no further change. These results support the strong beneficial effect of Alb therapy in focal ischemia and suggest its possible utility in treating patients with acute ischemic stroke. Supported by AHA Init. Invest. Award, NIH Grant NS05820 and an equipment loan from Moor Instruments, Ltd.