Reduction of Leukocyte Microvascular Adherence and Preservation of Blood-Brain Barrier Function by Superoxide-Lowering Therapies in a Piglet Model of Neonatal Asphyxia

Conclusion: Using three different strategies to either prevent formation or enhance elimination of O2⋅_ during the post-asphyxial period, we saw both reduced leukocyte adherence and preserved BBB function with treatment. These findings suggest that agents which lower O2⋅_ in brain may be attractive new therapeutic interventions for the protection of the neonatal brain following asphyxia. Introduction Asphyxia is a relatively common source of neonatal brain damage (1), affecting ~2 in every 1,000 births (2). The hypoxic ischemia resulting from this oxygen deprivation can produce long-term sequelae, including intellectual disability and neurologic deficits, and nearly a quarter of neonatal deaths worldwide are attributable to birth asphyxia (2). A dominant response to ischemia is inflammation (2, 3), resulting from the accumulation of circulating leukocytes in the cerebral microvasculature and their subsequent extravasation into brain parenchyma (4–7). The mechanisms promoting the early increase in leukocyte-endothelial interactions in the cerebral circulation await further elucidation, but probable causes include the elaboration of cytokines and chemokines (8, 9), and other proinflammatory mediators (10). There is also consensus that reactive oxygen species (ROS), formed during reperfusion following transient ischemia, including in the neonatal brain, also modulate inflammation (11–13). ROS are generated in multi...
Source: Frontiers in Neurology - Category: Neurology Source Type: research