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

Limits of Autoregulation• Impaired Cerebral Vascular Perfusion

• Disruption of the Blood-Brain Barrier

•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

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