Class A, 27- to 30-kg male hounds were administered an initial intravenous bolus (10% of the total dose [200 mg]) of generation-six polyamidoamine dendrimer (6.7 nm) labeled with cyanine 5, and cardiopulmonary bypass with peripheral cannulation was initiated. After 90 minutes of HCA, 70% of the total dose was infused over a 6-hour period. The final 20% of the total dose was given 24 hours post-HCA. The brain was harvested 48 hours later (72 hours post-HCA) and analyzed for dendrimer 6-cyanine 5 biodistribution.
The dorsal hippocampus demonstrated the highest brain accumulation of dendrimer 6-cyanine 5, which closely corresponds to the distribution of apoptotic neurons evident with histologic staining and on confocal imaging. In injured brain regions, dendrimer traversed the blood-brain barrier and localized within the target cells (injured neurons and microglia).
These findings have exciting implications for the future development of novel therapeutics to mitigate neurocognitive deficits in this group of patients.