Cerebral blood flow regulation

Knowledge of cerebral blood flow regulation, and the relationship between cerebral blood flow and cerebral metabolism, has had a major influence on the understanding of the pathophysiology of impaired perfusion reserve and acute ischemic stroke (Frackowiak 1986 Marchal et al. 1996 Baron 2001 Rutgers et al. 2004). 

Brain temperature also depends on regional cerebral blood flow (rCBF). Following vascular occlusion, deep brain tissues may suffer a transient temperature rise reflecting the failure of arterial blood to remove metabolic heat (28). As superficial tissues cool, the temperature in deep tissues also decreases. Thus, by retarding or interrupting blood flow, ischemia upsets temperature regulation. 

Flow to the brain tissue is precisely regulated by a process of autoregulation, according to local chemical conditions. Cerebral blood vessels dilate and so increase blood flow in response to decreased pH and arterial PO2 and to increased arterial PCO2, conditions associated with increased metabolic activity. The neurones are very sensitive to changes in cerebral blood flow interruption of flow for a few seconds causes unconsciousness. 

Herning RI, Better W, Nelson R, Gorelick D, Cadet JL. The regulation of cerebral blood flow during intravenous cocaine administration in cocaine abusers. Ann NY Acad Sci 1999 890 489-94. 

Knowledge of the anatomy of the blood supply of the brain is often helpful in understanding the etiology and mechanisms of TIA and stroke, which enable accurate targeting of acute treatment and secondary prevention. An awareness of the mechanisms underpinning the regulation of cerebral blood flow allows the clinician to identify patients at risk of stroke and assess the possible effects of treatments. 

Strandgaard S, Paulson OB (1992). Regulation of cerebral blood flow in health and disease. Journal of Cardiovascular Pharmacology 19 ... 

KlatzD 1 (1994) Evolution of brain edema concepts. Acta Neurochir Suppl (Wien) 60 3-6 Koehler RC, Roman RJ, Harder DR (2009) Astrocytes and the regulation of cerebral blood flow. Trends Neurosd 32 160-169... 

Guillot, F.L. and Audus, K.L. (1990) Angiotensin peptide regulation of fluid-phase endocytosis in brain microvessel endothelial cell monolayers. Journal of Cerebral Blood Flow and Metabolism, 10, 827-834,... 

The molecular structure of the smooth muscle Kjr channel is unknown, although, based on its properties, it is likely to be a member of the IRK family. Inward rectifier potassium currents have been identified in small cerebral, coronary (see Fig. 2A), and mesenteric arterioles (<200 i.m diameter). The presence of K[r channels may be a common feature in small arteries that determine in large part peripheral vascular resistance. It is not known if Kjr channels are exclusively present in small arteries, although they have not yet been reported in larger vessels. Innervation of this size artery (<100-200 j.m) is usually sparse and therefore small arteries may be more prone to respond to metabolic demand from the tissue, as reflected by potassium efflux. Thus, the appearance of K,r channels may reflect a transition of blood flow regulation to local (tissue) control. This is an intriguing hypothesis that remains to be tested. It will be important to study systematically the distribution of the K r channel within a vascular bed, as this may have physiological consequences. Kir channels, like K and K jp channels. 

Previous Work. As shown by the results of many experimentors, cerebral blood flow rate (under normal blood pressure conditions) is primarily determined by the C02 tension in arterial blood (12,14, 21, 22, 45, 46). The pH value of the extracellular fluid in brain is regarded as an essential factor for regulating vascular diameter (47, 48, 49,50). Cerebral hypoxia causes the C02-dependent regulation of the cerebral blood flow to change or vanish (9, 21, 25, 40, 45, 46, 51, 52). 

Ventilation relation similar to Gray (27) with venous pC02 and arterial p02 taken as regulated variables total blood flow was taken as constant cerebral blood flow and tissue blood flow were regulated by both arterial pC02 and p02. 

Cerebral blood flow and muscle blood flow regulated by arterial pCo2. 

In the brain, NO acts both as a neurotransmitter and as a paracrine hormone. Its functions involve regulation of synaptogenesis, synaptic plasticity, memory formation, cerebral blood flow, olfaction, visual transduction, and neuroendocrine secretion (Schmidt and Walter, 1994). In brain ischemia-reperfusion phenomena -NO has been reported to serve a protective role by inducing vasodilation and reducing neutrophil/platelet adhesion and aggregation, thus leading to increased blood flow, tissue perfusion, and attenuation of the ischemic insult. -NO may also protect the patient from ischemic-induced brain injury by -NO-mediated down-modulation of N-methyl-D-aspartate (NMDA) receptors, thus diminishing NMDA-induced neurotoxicity (Lipton et al., 1993 Choi, 1993 Wink et al., 1993). 

---