Neuronal injury and leukocyte accumulation in piglet brain after photothrombosis of the common carotid artery

Thromboembolic events are a major cause of ischemic stroke. Children experience thromboembolic stroke after neck trauma, cardiopulmonary bypass, and with heart disease and hypercoagulable states. This pilot study was performed to examine the neuropathology produced by partial common carotid artery thrombosis (CCAT) in a non-rodent, pediatric animal model. Methods: The left CCA was exposed in fentanyl anesthetized piglets (6-8kg, n=2). Partial CCAT was achieved by directing an argon laser over a 5 mm portion of the left CCA while erythrosin B, a photosensitizing dye, 20mg/kg iv was infused. This procedure in rodents forms a transient platelet thrombus in the CCA, which resolves within 30-60 minutes. After 3 (piglet 1) and 12 hours (piglet 2), brains were processed for H&E staining for light microscopy. Results: In piglet 1, numerous clumps of up to 25 leukocytes (without platelets) were seen within the lumen of the left CCA 3 hours after CCAT. A modest number of ischemic neurons were seen in the deep gray layers of the cortex bilaterally, most impressively in the anterior cerebral and anterior middle watershed regions. Piglet 2 inadvertently suffered a brief (2 minute) respiratory arrest 30 minutes after CCAT. Twelve hours after CCAT, no leukocyte clumps were seen in the left CCA, however, extensive neuronal damage was found throughout the cortex. As in piglet 1, damage was present in both hemispheres but was worse on the side of CCAT. Two deep cortical venules were completely occluded with leukocytes, while other patent vessels also contained intraluminal leukocytes. The hippocampus and caudate were normal in both piglets, however, small areas of ischemic cell injury were seen in the thalamus of piglet 2. Conclusion: CCAT is followed by ischemic changes in deep cortical neurons and leukocyte accumulation in cerebral vessels. When CCAT is followed by a brief hypoxic-ischemic insult, extensive neuronal damage occurs along with complete plugging of microvessels with leukocytes. These findings suggest a relationship between platelet activation and leukocyte-endothelial interactions in the pathogenesis of thromboembolic stroke.