CEREBRAL CIRCULATION
Dr. Jean Fredrick
Assistant Professor
Department of Physiology,
MGMCRI, Puducherry
Learning Objectives
At the end of this session , You should be able to
• List the special features of cerebral circulation.
• Name the methods of measurement of cerebral blood flow and give
the principles of measurement.
• Understand the regulatory mechanisms of cerebral circulation.
• Appreciate the importance of autoregulation of cerebral blood flow
• Know the basic pathophysiology of stroke and learn the
physiological basis of their treatment.
Venous Drainage - Occurs by deep veins and dural sinuses. They drain
into the internal jugular veins.
Innervation of Cerebral Vessels
1) Sympathetic Supply
• Sympathetic fibers are vasoconstrictors. Cell bodies of sympathetic
neurons are located in superior cervical ganglia.
• They release norepinephrine and neuropeptide Y at their nerve endings.
2) Parasympathetic Supply
• Causes vasodilation. These fibers secrete acetylcholine, VIP and
PHM–27.
• Cell bodies of cholinergic neurons are present in sphenopalatine
ganglia.
3) Sensory Neurons
• The sensory nerves contain substance P, CGRP, neurokinin A
and VIP which cause vasodilation.
• Cell bodies of sensory neurons are located in trigeminal ganglia.
The cerebral blood vessels are highly sensitive to pain. Pressure
on cerebral blood vessels causes pain.
Cerebral Blood Flow
Normal Values of CBF:
• The total cerebral blood flow is 750 ml per minute,
which is about 14% of cardiac output.
• This accounts for about 54 ml of blood per 100 gm of
brain tissue per minute.
• Oxygen consumption of brain is about 45 ml per
minute, which is about 3.3 ml per 100 g per minute.
Cerebral Blood Flow
• Cerebral blood flow is essential for the brain to carry out all the
important functions
– Cardiovascular and respiratory centers – Brain stem.
– Visceral functions and regulation of body temperature -
Hypothalamus
– Cognitive functions including language and speech – Cerebral
cortex.
– Sensory processing, motor activities and behavioral functions
are integrated in different parts of the brain.
Cerebral Metabolism
• Adequate blood supply to brain tissue should be maintained.
• Brain tissue is highly sensitive to hypoxia.
• The stoppage of blood flow > 15-30 seconds – unconsciousness &
> 5 minutes causes irreversible damage (leads to coma).
• Glucose - main fuel. Prolonged hypoglycemia results in cerebral
dysfunction.
• The metabolic requirements of brain remain fairly constant
irrespective of activities of the brain tissue and cerebral blood flow
(CBF).
CEREBRAL BLOOD FLOW
Special Features of CBF
1. Cerebral arteries are end arteries.
2. Increase in cerebral blood flow (arteriolar dilatation) is usually
associated with comparable increase in venous outflow.
3. In the brain, volume of blood and extravascular fluid remains
relatively constant.
4. The capillaries in brain are mostly non-fenestrated.
5. The cerebral blood vessels are surrounded by end-feet
processes of astrocytes which provides anatomical basis for the
formation of blood-brain barrier.
BBB provides protection to the brain from the toxic and
harmful substances circulating in the blood.
6. The mechanism for vesicular transport from blood into brain tissue
via endothelial wall of the cerebral blood vessels is less developed.
7. The tight junctions between the endothelial cells of capillaries are
very tight and do not permit the passage of substances through them.
The basement membrane of capillaries is also thick.
Measurement of CBF
Cerebral blood flow (CBF) can be measured by various methods. The
important methods are:
1. Kety method
2. By using radioactive substances
3. By using flow meters
4. Positron emission tomography (PET)
5. Single photon emission computerized tomography (SPECT)
1) Kety Method
• This method uses Fick’s principle.
• The subject inhales 15% of nitrous oxide for 10 minutes. The arterial
sample and the venous sample (from internal jugular bulb) are
collected and the arteriovenous difference is measured.
Amount of nitrous oxide taken by the brain
CBF = ---------------------------------------------------------------------------
Arteriovenous difference of nitrous oxide across the brain
2) Using Radio Active Substances
• Radioactive Xenon (133Xe).
• The substance is injected into the carotid artery and the radioactivity
of different areas of the brain is measured by placing scintillation
counters around the skull. This is a useful method for studying the
regional distribution of CBF in different parts of the brain.
3) Using Flowmeters
• The flowmeters can be directly placed in the cerebral arteries in
experimental animals or in patients undergoing neurosurgery and
CBF can be measured accurately.
4) Positron Emission Tomography (PET)
• This is mainly used for monitoring regional blood flow of various
parts of the brain.
• In this method, a short-lived radioisotope is used to label a
substance, which is injected.
• Scintillation detectors placed on the head monitor the appearance
and clearance of the tracer.
• The information from detectors is processed in a computer that
quantifies the flow in a particular region of the brain.
• Single photon emission computerized tomography (SPECT) is also
used for the purpose.
5) Magnetic Resonance Imaging (MRI)
• This technique is based on detecting resonant signals from different
tissues in magnetic field. The resolution of MRI is better than the
PET.
• Recently, developed fMRI (functional magnetic resonance
imaging), measures blood supply to a specific area of the brain.
Regulation of CBF
1) Role of Intracranial Pressure
• The brain tissue and cerebrospinal fluid (CSF) are incompressible.
Thus, at any given time, the total volume of blood, CSF volume and
brain tissue in the cranial cavity remains constant. This is called
Monro-Kellie doctrine.
– Rise in intracranial pressure results in compression of cerebral
arteries that decreases blood flow.
– Increase in arterial pressure as occurs during downward acceleration,
increases arterial pressure in the head. However, ICP also rises
simultaneously. Increased ICP prevents rupture of blood vessels by
supporting them.
• In brain tumors, compression of cerebral vessels decreases blood
flow. Decreased blood flow causes hypoxia at vasomotor center. This
activates Cushing’s reflex, which attempts to restore cerebral blood
flow.
2) Neural Regulation
• Stimulation of sympathetic fibers causes vasoconstriction, but it is
not important, as the vasoconstrictor system is not well developed in
cerebral vascular bed. Parasympathetic stimulation causes
vasodilation.
3) Metabolic Regulation
• CBF is altered by production of local vasodilator metabolites like
potassium, hydrogen, and adenosine.
• Acidosis, hypoxia, and hypercapnia in the brain tissue produce
potent vasodilation and thereby blood flow.
• It has been demonstrated that 70% increase in arterial pCO2
approximately doubles the CBF.
ROLE OF ASTROCYTES: With increase in neuronal activity, chemical
substances (nitric oxide, metabolites of arachidonic acid, K+,
adenosine) are released from astrocytes which causes vasodilation
and increases cerebral blood flow.
4) Autoregulation
• CBF remains relatively constant within a pressure range of 60 - 140
mmHg.
• The autoregulation may be due to neural and metabolic factors.
CLINICAL ASPECTS
Stroke: rapid onset of neurological deficit that is attributable to a
focal vascular cause.
• As per WHO definition, stroke is a rapidly developing clinical signs
of focal (or global) disturbance of cerebral function with symptoms
lasting for 24 hours or longer or may leading to death with no
apparent cause other than of vascular origin.
• Progressive stroke (stroke in evolution) is the one in which
neurological deficit worsens after the patient first present and in
complete stroke neurological deficit does not progress beyond 96
hours.
Types of Strokes:
1) Ischemic stroke
2) Hemorrhagic stroke.
About 70% of stroke is ischemic stroke, 17% is hemorrhagic
strokes and 3% is others that include venous sinus thrombosis, AV
malformations, aneurysms etc.
1) Ischemic Stroke
• Occurs due to blockage of a cerebral artery by
thromboembolism.
• Cerebral infarction is most commonly caused by thromboembolic
disease.
2) Hemorrhagic Stroke
• Bleeding directly into the brain tissue.
• Due to rupture of a branch of cerebral artery at the site of aneurysm.
• Rupture of Charcot’s artery (the artery of cerebral hemorrhage)
i.e. the lenticulostriate branch of middle cerebral artery (at internal
capsule) is the common cause of stroke that produces contralateral
hemiplegia.
Treatment of Stroke
• Intravascular Thrombolysis: Fibrinolytic drugs(Recombinant t-
PA) given early in the course of stroke is very useful.
• Endovascular Mechanical Thrombectomy: Very useful, especially
if there is contraindication for thrombolysis.
• Anticoagulation therapy for acute ischemic stroke: Done in patients
with high risk of early cardiogenic re-embolization. And in cerebral
venous thrombosis.
• Antiplatelet Therapy: Aspirin, 175mg daily reduces stroke related
morbidity and prevents early stroke recurrence.
• Antiexcitotoxic Drugs: Normally, brain cells take up and utilize
glutamate. Ischemia of brain tissue decreases glutamate uptake that
increases local glutamate concentration. Glutamate causes
excitotoxic neuronal damage of the brain tissue (excitotoxic
lesion). Therefore, antiexcitotoxic drugs are quite helpful in the
treatment of stroke.
• Supportive care: Maintenance of blood pressure, serum glucose,
control of ICP, catheterization, prevention of complications and
physiotherapy plus other measures of neurorehabilitation.
