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Nasally delivered VEGFD mimetics mitigate stroke-induced dendrite loss and brain damage.

ABSTRACT: In the adult brain, vascular endothelial growth factor D (VEGFD) is required for structural integrity of dendrites and cognitive abilities. Alterations of dendritic architectures are hallmarks of many neurologic disorders, including stroke-induced damage caused by toxic extrasynaptic NMDA receptor (eNMDAR) signaling. Here we show that stimulation of eNMDARs causes a rapid shutoff of VEGFD expression, leading to a dramatic loss of dendritic structures. Using the mouse middle cerebral artery occlusion (MCAO) stroke model, we have established the therapeutic potential of recombinant mouse VEGFD delivered intraventricularly to preserve dendritic architecture, reduce stroke-induced brain damage, and facilitate functional recovery. An easy-to-use therapeutic intervention for stroke was developed that uses a new class of VEGFD-derived peptide mimetics and postinjury nose-to-brain delivery.

SUBMITTER: Mauceri D 

PROVIDER: S-EPMC7165430 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Nasally delivered VEGFD mimetics mitigate stroke-induced dendrite loss and brain damage.

Mauceri Daniela D   Buchthal Bettina B   Hemstedt Thekla J TJ   Weiss Ursula U   Klein Christian D CD   Bading Hilmar H  

Proceedings of the National Academy of Sciences of the United States of America 20200330 15

In the adult brain, vascular endothelial growth factor D (VEGFD) is required for structural integrity of dendrites and cognitive abilities. Alterations of dendritic architectures are hallmarks of many neurologic disorders, including stroke-induced damage caused by toxic extrasynaptic NMDA receptor (eNMDAR) signaling. Here we show that stimulation of eNMDARs causes a rapid shutoff of <i>VEGFD</i> expression, leading to a dramatic loss of dendritic structures. Using the mouse middle cerebral arter  ...[more]

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