Nasally delivered VEGFD mimetics mitigate stroke-induced dendrite loss and brain damage.
Daniela MauceriBettina BuchthalThekla J HemstedtUrsula WeissChristian D P KleinHilmar BadingPublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
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.
Keyphrases
- atrial fibrillation
- cerebral ischemia
- vascular endothelial growth factor
- resting state
- white matter
- middle cerebral artery
- high glucose
- diabetic rats
- oxidative stress
- randomized controlled trial
- functional connectivity
- endothelial cells
- poor prognosis
- blood brain barrier
- subarachnoid hemorrhage
- high resolution
- brain injury
- internal carotid artery
- long non coding rna
- loop mediated isothermal amplification