The neurovascular unit and systemic biology in stroke - implications for translation and treatment
- PMID: 36085420
- DOI: 10.1038/s41582-022-00703-z
The neurovascular unit and systemic biology in stroke - implications for translation and treatment
Abstract
Ischaemic stroke is a leading cause of disability and death for which no acute treatments exist beyond recanalization. The development of novel therapies has been repeatedly hindered by translational failures that have changed the way we think about tissue damage after stroke. What was initially a neuron-centric view has been replaced with the concept of the neurovascular unit (NVU), which encompasses neuronal, glial and vascular compartments, and the biphasic nature of neural-glial-vascular signalling. However, it is now clear that the brain is not the private niche it was traditionally thought to be and that the NVU interacts bidirectionally with systemic biology, such as systemic metabolism, the peripheral immune system and the gut microbiota. Furthermore, these interactions are profoundly modified by internal and external factors, such as ageing, temperature and day-night cycles. In this Review, we propose an extension of the concept of the NVU to include its dynamic interactions with systemic biology. We anticipate that this integrated view will lead to the identification of novel mechanisms of stroke pathophysiology, potentially explain previous translational failures, and improve stroke care by identifying new biomarkers of and treatment _targets in stroke.
© 2022. Springer Nature Limited.
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References
-
- Lo, E. H., Dalkara, T. & Moskowitz, M. A. Mechanisms, challenges and opportunities in stroke. Nat. Rev. Neurosci. 4, 399–415 (2003). - PubMed
-
- Lo, E. H., Broderick, J. P. & Moskowitz, M. A. tPA and proteolysis in the neurovascular unit. Stroke 35, 354–356 (2004). - PubMed
-
- Yemisci, M. et al. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat. Med. 15, 1031–1037 (2009). - PubMed
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