Cerebral Blood Flow
Anatomy of Cerebral Circulation
Ophthalmic v.
•Activation of endothelial cells and glia occurs at least 2
days after ischemia, and capillary buds form by 7 days.
•Microvascular density, which relates to newly formed
vessels, correlates with the survival time after the onset of
ischemic stroke in humans
acidic and basic fibroblast growth facto (aFGF and
bFGF), transforming growth factor (TGF), vascular
endothelial growth factor (VEGF), platelet-derived
growth factor (PDGF), platelet-derived endothelial cell
growth factor (PD-ECGF), insulin-like growth factor
(IGF)
Autoregulation
•Autoregulation of blood flow is a regulatory mechanism that
allows blood flow in most vascular beds to remain relatively
constant during variations of arterial pressure.
•This is particularly well developed in the brain since it requires
a high degree of homeostasis with respect to a balance of tissue
nutrients and fluids
Limits of Autoregulation
• Impaired Cerebral Vascular Perfusion
• Disruption of the Blood-Brain Barrier
Mechanism of Autoregulation
• Myogenic Hypothesis
– Smooth muscle in resistance
arteries
• Metabolic Influence
– O2, CO2, H+, Adenosine, K+ and
Ca2+
– A definitive role for any one of
these factors remains to be
demonstrated.
• Endothelial Factors
– Endothelium
– Endothelium derived relaxing
factor (nitric oxide), Endothelium
derived contracting factor
Regulation of Cerebral Blood Flow by O2
Regulation of Cerebral Blood Flow by CO2
Modulation of Autoregulation
• Autonomic Nerves
– Sympathetic
– Parasympathetic
– Trigeminovascular System
• The Renin-Angiotensin System
– Angiotensin
– similar to sympathetic regulation
Regulation of Cerebral Blood Flow by
The Sympathetic Nervous System
Regulation of Cerebral Blood Flow by
The Parasympathetic Nervous System
Direct stimulation of the facial nerve leads to an
increase in total cranial blood flow, however the
phsiological role is not clear. The nerves are not
directly involved in the most basic
cerebrovascular responses, such as hypoxic or
hypercapnic vasodilation, nor do thay appear to
play a role in autoregulation
Regulation of Cerebral Blood Flow by The
Trigeminovascular System
This system is the sole sensory innervation of
the cerebral vessels. Its function does not
appear to be in the maintenance of resting
cerebral flow. In situations of abnormal
physiology, this system comes into play by
mediating vasodilation.
Consequence of Chronic Hypertension
The autoregulatory plateau of the pressure-flow relation is shifted
to the right in hypertensive patients and experimental animals so
that cerebral blood flow may be normal despite very high levels of
blood pressure
Vasoactive Mediators of Cerebral Vessels
• Amines + vasoconstriction
– Norepinephrine (+) - vasorelaxation
– Serotonin (+-)
– Histamine (-)
– Dopamine (-)
– Acetylcholine (-)
• Lipid Mediators
– Eicosanoids
• Prostacyclin (-)
• Thromboxane A2 (+)
• Prostaglandins (PGD2, PGE2(-), PGF2(+))
– Leukotrienes (+)
– Platelet-Activating Factor (- +)
• Peptides
– Vasodilator Peptides (-)
• Vasoactive Intestinal Peptide (VIP)
• Calcitonin Gene-Related Peptide (CGRP)
• Adrenomedullin
• Substance P (SP)
• Bradykinin
– Vasoconstrictor Peptides (+)
• Neuropeptide-Y (NPY)
• Angiotensin-II (ATII)
• Endothelin-1 (ET1)
• Vasopressin (VP)
• Purine Nucleotides (-)
– Adenosine
– ADP and ATP
• Gases (-)
– Nitric Oxide (NO)
– Carbon Monoxide (CO)
Biology of Cerebral Vascular
Muscle
Cerebral Microcirculation
Cerebral Spinal Fluid
•Formed at the choroid plexus and drained into
the peripheral blood stream at the arachnoid villi.
•CSF volume is completely cleared via this bulk
flow process in the human brain every 4-5 hr.
Blood-Brain Barrier
Edema