ArticleThe Annals of thoracic surgery2016
Nanotechnology Approaches to Targeting Inflammation and Excitotoxicity in a Canine Model of Hypothermic Circulatory Arrest-Induced Brain Injury.
Article in The Annals of thoracic surgery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Inflammatory profile in a canine model of hypothermic circulatory arrest.The Journal of surgical research · 2021Article
- Inhaled nitric oxide reduces injury and microglia activation in porcine hippocampus after deep hypothermic circulatory arrest.The Journal of thoracic and cardiovascular surgery · 2021Article
- Systemic dendrimer-drug nanomedicines for long-term treatment of mild-moderate cerebral palsy in a rabbit model.Journal of neuroinflammation · 2020Article
- Targeting Mitochondrial Dysfunction and Oxidative Stress in Activated Microglia using Dendrimer-Based Therapeutics.Theranostics · 2018Article
- Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury.Scientific reports · 2017Article
- Generation-6 hydroxyl PAMAM dendrimers improve CNS penetration from intravenous administration in a large animal brain injury model.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
- Nanoscale effects in dendrimer-mediated targeting of neuroinflammation.Biomaterials · 2016Article
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12 authors.
Funding
Abstract
backgroundNeurocognitive dysfunction and injury remain problematic after cardiac procedures requiring hypothermic circulatory arrest (HCA). Due to poor blood-brain barrier penetrance and toxicities associated with systemic drug therapies, clinical success has been elusive. Accordingly, we explored targeted dendrimer (a nanoparticle) drug therapies in our well-established canine model of HCA to characterize the biodistribution and cellular localization of these nanoparticles in areas of known neuronal apoptosis and necrosis.
methodsClass 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.
resultsThe 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).
conclusionsThese findings have exciting implications for the future development of novel therapeutics to mitigate neurocognitive deficits in this group of patients.
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