Unveiling the Systemic Drivers of Blood-Brain Barrier Disruption in Sickle Cell Disease: Insights from Proteomic Profiling

This study demonstrates increased blood-brain barrier (BBB) permeability in adults with sickle cell disease (SCD) using dynamic contrast-enhanced MRI.
Proteomic analysis identified 79 plasma proteins associated with BBB injury, implicating pathways related to iron homeostasis, hypoxia response, immune dysregulation, extracellular matrix degradation, lipoprotein metabolism, and arginine-proline metabolism.
BBB disruption and cerebral hypoxia synergistically contribute to white matter microstructural injury detectable by MRI metrics, correlating with silent cerebral infarcts.
Targeting systemic pathways that disrupt the BBB may offer novel strategies to mitigate brain injury and cognitive decline in SCD patients.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

This study demonstrates increased blood-brain barrier (BBB) permeability in adults with sickle cell disease (SCD) using dynamic contrast-enhanced MRI.
Proteomic analysis identified 79 plasma proteins associated with BBB injury, implicating pathways related to iron homeostasis, hypoxia response, immune dysregulation, extracellular matrix degradation, lipoprotein metabolism, and arginine-proline metabolism.
BBB disruption and cerebral hypoxia synergistically contribute to white matter microstructural injury detectable by MRI metrics, correlating with silent cerebral infarcts.
Targeting systemic pathways that disrupt the BBB may offer novel strategies to mitigate brain injury and cognitive decline in SCD patients.

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