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BRAIN & KIDNEY 2020ANATOMICAL AND PHYSIOLOGICAL

CONSIDERATIONS

Kumar Rajamani, MD, DM

Professor of Neurology

WSU School of Medicine-Detroit

5.8.2020

Disclosures1)Site PI – NIH though StrokeNett- ARCADIA &

Sleep-Smart Trials.

2)Co Investigator –In vivo MRI assessments ofsmall vessels- ‘USPIO’ – study. – NIH1RO1NS108491-01

3)Post Marketing Surveillance of the AmplazterDevice- PFO closure in Cryptogenic Strokepatients- Abbot Inc.

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BACKGROUND

➢ The brain and kidneyshare unique susceptibility to vascular disease

➢ Complex Interplay between Brain & Kidney

➢ Similarities in vasoregulation of the microvasculature of both organs

Toyoda & Ninomiya Lancet Neurology 2014;13:823-832

AIMS & OBJECTIVES➢Functional anatomy of the Cerebral Blood

Vessels

➢Functional anatomy of the Kidney Circulation

➢Ultrastructural Features-Microvasculature

➢The Neurovascular Unit

➢Brain as an Excretory organ ? - The Glymphatic System

➢Future Directions-Imaging the microvasculatureDO N

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Cerebral Circulation

➢ Anterior circulation –supplies the neocortex– evolutionarily younger

➢ Posterior Circulation predominantly the brain stem & cerebellum

➢ Circle of Willis

Wei Ling Lau, B Huisa and Mark Fisher,2017 Transl Stroke Res, 8:67–76

Renal Circulation➢ Renal artery direct

branch of the aorta

➢ 3-5 Segmentalarteries

➢ Interlobar arteries runsbetween therenal pyramids

➢ Arcuate Arteries between the renal cortex & medulla

Wei Ling Lau, B Huisa and Mark Fisher,2017 Transl Stroke Res, 8:67–76DO N

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Microvasculature of the human cerebral white matter

Ø D e n s e surface networkof pial arteries

Ø M a n y arterial branches terminate in the cortex and subcortical white matter

Ø S o m e large vessels run down in a straight line towards the lateral ventricle(No centrifugalvNeonsaskealest.)al

Neuropathology, 23( 2);111-118, 2003.

J Neuropathol Exp Neurol, Vol 62, Feb2003

Microvasculature of the human cerebral cortex

➢ Capillary networksdenser in cortex

➢ Arteries penetratestraightdown onto gyralwhite matter

➢ Most arteries terminate in the cortex or subcortical white matter

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Cerebral Microvasculature is notUniform

➢ Perilous blood supply

➢ Some areas more vulnerable than others

➢ Long medullary arterioles-deep WM

➢ Short medullary vessels- corpus callosum, ‘U’ fibers

Neuropathology and Applied Neurobiology (2011), 37, 56–74AJNR Am J Neuroradiol 1990; 11: 431–9

The Brain & Kidney are both pulsatile organs

➢Unlike most other organs, the kidneys andthe brain pulsate in rhythm with the heartbeat

➢They are both low resistance end organs

➢Both are consequently exposed to continuous blood through out the cardiac cycle

➢Both get very high volume blood flow for them to to do their function

Stroke. 2008;39:5-6, Stroke 2008;39:56-61DO NOT

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The Brain & Kidney are both pulsatile organs

Terem et al. Revealing sub-voxel motions of brain tissue using phase-based amplified MRI (aMRI) MRI Med. 2018, Dec;80(6):2549-2559- “amplified”MRI

“Strain Vessel” Hypothesis

➢ Juxtamedullary Glomerular Afferent arterioles, central retinal artery & perforators of MCA-ACA & PCA

➢ therefore have to maintain a strong vascular tone

➢ from the hemodynamic point of view, these are small and short vessels

➢ that are exposed to a high pressure and

➢ in order to provide a large pressuregradient in a short distanceDO N

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STRAIN-VESSEL HYPOTHESIS-KIDNEY

➢ Juxtamedullary nephrons are more prone to hypertensive injury

➢ They have to deal with very higher pressures

➢ Maintain high vascular tone

Ito et al, HYPERTENSION RESEARCH -2009

STRAIN VESSEL HYPOTHESIS-CNS

➢ Analogousto the glomerular afferent arterioles are the perforating end vessels of the brain and the central retinal artery

➢ Are exposed to high pressureand have to maintain strong vascular tone in order to provide large pressure gradients from the parent vessels to the capillaries.

Ito et al. HYPERTENSION RESEARCH -2009DO NOT

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Costantino Iadecola. Circulation Research. Neurovascular and Cognitive Dysfunction in Hypertension, Volume: 124, Issue: 7, Pages: 1025-1044, DOI: (10.1161/CIRCRESAHA.118.313260) © 2019 American Heart Association, Inc.

Adaptive Responses to protect downstream Microvessels

Costantino Iadecola. Circulation Research. Neurovascular andCognitive Dysfunction in Hypertension, Volume: 124, Issue: 7,Pages: 1025-1044, DOI: (10.1161/CIRCRESAHA.118.313260) © 2019 American Heart Association, Inc.

Cerebral Autoregulation

Ø T h e cellular basis is the vascular smooth cell

Ø M yo g e n i c responseofBayliss-cells constrict inresponse to increases intransmural pressure

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Autoregulation in the Kidneys

➢ The brain and kidney are similar in that bothorgans have high blood flow rates and havelocal autoregulation

➢ Autoregulation allows constant renal blood flow despite fluctuations in BP and maintains GFR in the kidney, prevents barotrauma of glomerular capillaries

➢ Macula densa tubuloglomerular feedback& myogenic reflexes of the vascular smooth muscle arterioles mediate this response.

Calstrom et al.Physiol Rev • VOL 95;2015:405-511

Brain Fluid Compartments

Jessen et al, Neurochem Res (2015) 40:2583–2599DO NOT

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THE NEUROVASCULAR UNIT

➢ Neurons, Astrocytes, and Endothelial cells form single functional unit (neurovascular unit) to maintain thehomeostasis of the brain’s internal milieu.

➢ Emphasizes the unique relationship between brain cells and the cerebral vasculature

Jessen et al, Neurochem Res (2015) 40:2583–2599 Iadecola C. Neuron, 2017

THE NEUROVASCULAR UNITprovides quick energy

➢ Brain needs a large amount of energy- lacks a reservoir to store fuel for use when needed-quickly and precisely

➢ This close coupling allows the brain to adjust its blood flow needs – at the right time, place and amount

Iadecola C. Neuron, 2017, 96(1): 17–42DO NOT

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The GLYMPHATIC System

Neurochem Res (2015) 40:2583–2599

Glymphatic system clears waste by Convection ForcesA: CSF enters the brain parenchyma via periarterial pathways by Convection, washes out solutes from the interstitial space and empties along the veins.

B: with Aging, there is loss of the polarity of the aquaporin channels on the astrocyte end feet and hence less effective Glymphatic System clearance

C: In AD- dilated Perivascular Spaces because of blocked spaces from accumulation of Beta Amyloid

Jessen et al, Neurochem Res (2015) 40:2583–2599Iadecola C. Neuron, 2017DO N

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Cerebral Angiogram

SWI in presence of Ferumoxytol (4mg/kg)

(mIP = 9mm)

Courtesy Prof Mark Haacke – WSU – MRI Research UnitDO NOT

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SWI(with overlays) SWI (mIP = 3mm) SWI (mIP = 6mm)

2a

1v

2v

1a1v

2v

2a

SWI (mIP = 12mm)

Major Vein  

MajorArtery

Post‐contrast SWI

1a

Ferumoxytol concentration = 4mg/kg

SWI

SWI (mIP = 3mm)

Cerebral vessels

SWI (mIP = 9mm)

Venous tributaries

Major Vein  

MajorArteryDO NOT

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CONCLUSIONS1) Functional similarities between the arterial

supply of the kidney and brain

2) Strain vessel hypothesis could explain how these vessels become vulnerable

3) The neurovascular unit helps meet energy the brains high energy demands

4) The glymphatic system is unique and important waste clearance system in the brain

5) Clinical Imaging of the small vessels is still challenging

THANKYOU

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