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Regulation of the Cerebral Circulation: Neurovascular coupling in the normal brain and in hypertensi

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Regulation of the Cerebral Circulation: Neurovascular coupling in the normal ... Deposition of amyloid B-peptide in neuropil (neurotic plaques) and blood vessels ... – PowerPoint PPT presentation

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Title: Regulation of the Cerebral Circulation: Neurovascular coupling in the normal brain and in hypertensi


1
Regulation of the Cerebral Circulation
Neurovascular coupling in the normal brain and in
hypertension, stroke, and Alzheimer disease
Girouard et al. J Appl Physiol.2006100328-35.
2
Outline
  • Define Key Terms
  • Cerebral Mechanisms
  • Disease Characteristics Mechanisms
  • Conclusion
  • Future Research

3
Neural (Brain) Terminology and Anatomy
  • Neurovascular Coupling
  • Cerebral Blood Flow (CBF)
  • Neurons

4
Neural (Brain) Terminology and Anatomy Cont…
  • Glia network of branched cells and fibers that
    generate signals initiating vasodilation support
    and protection for neurons supporting cells of
    nervous system
  • Astrocytes large glia
  • Oligodendrocytes smaller than astrocytes but
    larger than microglia
  • Microglia small glia

5
CNS Microglial Cells…
  • Astrocyte

6
Astrocyte Role in Metabolism
7
CNS Microglial Cells…
  • Oligodendrocyte
  • Support
  • axons
  • Produce
  • myelin
  • sheath
  • Microglia- Smallest glial cells
  • Some clean-up brain debris
  • Most serve as immune system of the brain
  • Protect brain from invading microorganisms

Reference http//members.tripod.com/blustein/inde
x.htm
8
Vascular Terminology
  • Vascular Cells
  • Endothelium
  • Smooth Muscle Cells
  • Pericytes/Adventitial cells
  • ALL convert signals to create vascular changes
    that lead to cerebral blood flow increases in
    activated area of brain

9
(No Transcript)
10
Working Together
Neurons Glia
Endothelial Cells Smooth Muscle Cells Adventitial
Cells
Functional Neurovascular Unit
11
What we will be looking at…
  • I. Normal Cerebral Blood Flow Relationships of
    cerebrovascular cells
  • II. Mechanism of Neurovascular Coupling
  • Ion Mechanisms
  • Energy Metabolism Mechanisms
  • Vasoactive Factors
  • III. Impaired Cerebral Blood Flow

12
Overall Schematic
  • Neurovascular Coupling

13
Blood Flow of Neural Circulation
Arteries

14
Potent Factors for Vasoactivation
  • NO
  • Endothelin
  • Free Radicals

15
Proposed Mechanisms
  • Ion Mechanism
  • Energy Metabolism
  • Mechanism
  • Vasactive Factor
  • Mechanism

16
Ion Mechanism
  • Action Potential (AP)
  • Ion Secretion
  • Release of extra cellular K/ H
  • Vasodilation
  • Relaxation
  • Katp
  • Adenosine and Prostacyclin role

17
Energy Metabolism Mechanism
  • Adenosine during
  • ATP catabolism
  • 2. Brain Activation
  • CBF
  • Lactate formation
  • H

18
Vasoactive Factors Mechanism
  • Induced AP
  • Glutamate Receptor Site
  • Produces vasodilation
  • CBF

19
Diseased States of Neurovascular Coupling
  • Hypertension
  • AD
  • Ischemic Stroke

20
HYPERTENSION
  • Alteration of vessels
  • Vascular and
  • Occlusions
  • Alteration of functional hyperemia

DISEASE CAN ALTER COGNITIVE FUNCTION
21
Alzheimer Disease (AD)
  • When cerebrovascular structure altered…
  • Deposition of amyloid B-peptide in neuropil
    (neurotic plaques) and blood vessels
  • Accumulation of hyperphosphorylated neurofilament
    (neurofilibrillary tangles)
  • Reduced number of microvessels
  • Endothelial cells flattened
  • Smooth muscle cell degeneration

22
Alzheimer's Disease cont…
  • B. When structural function is altered...
  • 1.
  • 2.
  • 3.
  • 4.
  • 5.

23
Alzheimers Disease cont…
  • ALL characteristics can lead to…
  • DECREASED PERFUSION
  • Ischemic lesions with AB exacerbate dementia
  • Decrease CBF alters AB tracking across blood
    brain barrier
  • Decrease in CBF promotes AB accumulation
  • Decrease in protein synthesis (CRITICAL in NORMAL
    brain function)

24
Ischemic Stroke
  • Cerebral Ischemia

After ischemic event… cerebral circulation
vasoparalysis (affecting CBF and metabolism)
25
Vasoparalysis of circulation
  • CBF
  • Vasomotor stimuli altered
  • Autoregulation impaired
  • CBF when functional activation occurs
  • Metabolism
  • Less oxidative response at cytochrome a in ETC
  • Glucose utilization

All result in oxidative stress in cerebral blood
vessels ROS???? And NADPH oxidase?????
26
Conclusion
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