NIH VideoCast - Translating Thought into Blood Flow in the Brain: Capillaries as Sensors of Neural Activity

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Translating Thought into Blood Flow in the Brain: Capillaries as Sensors of Neural Activity

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Air date:	Wednesday, October 14, 2020, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 558 (296 Live, 262 On-demand)
Category:	WALS - Wednesday Afternoon Lectures
Runtime:	01:00:22
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	NIH Director's Wednesday Afternoon Lecture Series Healthy brain function depends on the finely tuned spatial and temporal delivery of blood-borne nutrients to active neurons via the vast, dense capillary network. Cerebral small vessel diseases (SVDs) are a central link between stroke and dementia—two co-morbidities that rank among the most pressing human health issues. Despite the emerging consensus that SVDs are initiated in the endothelium, the early molecular mechanisms remain largely unknown and no specific treatments are yet available. Deficits in on-demand delivery of blood to active brain regions (functional hyperemia) have been identified as early manifestations of the underlying pathogenesis. The strong inward-rectifier K+ channel (Kir2.1) in capillary endothelial cells, which senses neuronal activity and initiates a propagating electrical signal that dilates upstream arterioles, is a cornerstone of this functional hyperemia mechanism. However, whether this mechanism is targeted in SVDs and how resulting signaling deficits might be rescued remains unknown. Using a genetic mouse model of the most common hereditary SVD (CADASIL, Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), we show that impaired functional hyperemia is caused by a complete loss of capillary-to-arteriole electrical signaling due to diminished capillary endothelial Kir2.1 channel activity. We further linked Kir2.1 deactivation to depletion of phosphatidylinositol 4,5-bisphosphate (PIP2), a membrane phospholipid essential for Kir2.1 activity. Strikingly, systemic injection of soluble PIP2 rapidly restored functional hyperemia in SVD, suggesting a possible strategy for rescuing functional hyperemia in brain disorders in which blood flow is disturbed.. For more information go to https://oir.nih.gov/wals/about-wals

NLM Title:	Translating thought into blood flow in the brain : capillaries as sensors of neural activity / Mark T. Nelson.
Author:	Nelson, Mark T. National Institutes of Health (U.S.),
Publisher:
Abstract:	(CIT): Healthy brain function depends on the finely tuned spatial and temporal delivery of blood-borne nutrients to active neurons via the vast, dense capillary network. Cerebral small vessel diseases (SVDs) are a central link between stroke and dementia--two co-morbidities that rank among the most pressing human health issues. Despite the emerging consensus that SVDs are initiated in the endothelium, the early molecular mechanisms remain largely unknown and no specific treatments are yet available. Deficits in on-demand delivery of blood to active brain regions (functional hyperemia) have been identified as early manifestations of the underlying pathogenesis. The strong inward-rectifier K+ channel (Kir2.1) in capillary endothelial cells, which senses neuronal activity and initiates a propagating electrical signal that dilates upstream arterioles, is a cornerstone of this functional hyperemia mechanism. However, whether this mechanism is targeted in SVDs and how resulting signaling deficits might be rescued remains unknown. Using a genetic mouse model of the most common hereditary SVD (CADASIL, Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), we show that impaired functional hyperemia is caused by a complete loss of capillary-to-arteriole electrical signaling due to diminished capillary endothelial Kir2.1 channel activity. We further linked Kir2.1 deactivation to depletion of phosphatidylinositol 4,5-bisphosphate (PIP2), a membrane phospholipid essential for Kir2.1 activity. Strikingly, systemic injection of soluble PIP2 rapidly restored functional hyperemia in SVD, suggesting a possible strategy for rescuing functional hyperemia in brain disorders in which blood flow is disturbed.
Subjects:	Brain--blood supply Capillaries--physiology Dementia--physiopathology Endothelium, Vascular--physiology Neurons--physiology
Publication Types:	Lecture Webcast

NLM Classification:	WL 302
NLM ID:	101773038
CIT Live ID:	38686
Permanent link:	https://videocast.nih.gov/watch=38686

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