Nicotine Raises the Influx of Permeable Solutes across the Rat Blood—Brain Barrier with Little or No Capillary Recruitment

Abstract

Summary: Nicotine (1.75 mg/kg s.c.) was administered to rats to raise local CBF (ICBF) in various parts of the brain, test the capillary recruitment hypothesis, and de termine the effects of this increase in lCBF on local solute uptake by brain. lCBF as well as the local influx rate constants (K I) and permeability-surface area (P S) pro ducts of e4C]antipyrine and [14C]-3-0-methyl-D-glucose (30MG) were estimated by quantitative autoradiography in 44 brain areas. For this testing, the finding of signifi cantly increased PS products supports the capillary re cruitment hypothesis. In 17 of 44 areas, nicotine treat ment increased lCBF by 30-150%, K I of antipyrine by 7-40%, KI of 30MG by 5-27%, PS product of antipyrine by 0-20% (mean 7%), and PS product of 30MG by 0-23% (mean 8%). Nicotine had no effect on blood flow or influx in the remaining 27 areas. The increases in lCBF and K IThe major purposes of blood circulation to and through the capillaries of the brain most certainly are the delivery of nutrients to cells and ligands to receptors and the removal from the parenchyma of locally produced metabolites , messenger mole cules, reactive species such as free radicals, and heat energy. In most instances, useful or meaning ful increases and decreases in blood flow would therefore be expected to be linked to changes in one or more of these functions. 687of antipyrine were significant, whereas those in KI of 30MG and in PS for both antipyrine and 30MG were not statistically significant. The lack of significant changes in P S products implies that in brain areas where nicotine increased blood flow: (a) essentially no additional capil laries were recruited and (b) blood flow within brain cap illary beds rises by elevating linear velocity. The KI re sults indicate that the flow increase generated by nicotine will greatly raise the influx and washout rates of highly permeable materials, modestly elevate those of moder ately permeable substances, and negligibly change those of solutes with extraction fractions of <0.2, thereby pre serving the barrier function of the blood-brain barrier.

Smoking as a risk factor for multiple sclerosis

“…18 Several mechanisms by which smoking could increase the risk for MS have been suggested, e.g. cyanide neurotoxicity, 19 nicotine related immune modulation, 20 nicotine related increased blood-brain barrier permeability, 21 post-translational protein modification in the lungs, 22,23 and other mechanisms. 13 Swedish snuff use has been associated with a decreased risk for MS, 13 and an interaction between smoking and HLA-DRB1*15 and HLA A*02 carriage (two genes encoding antigen presenting molecules) regarding MS risk has been shown.…”

Lifestyle Factors and Multiple Sclerosis: A Case-Control Study in Belgrade

“…The biological basis of the potential link between smoking and MS has not been fully elucidated yet. One of the possibilities is a direct effect of cigarette smoke components on the blood-brain barrier, since nicotine has been shown to increase the microvascular blood flow in the brain and to cause leakage of the blood-brain barrier in rats [16,17] . Another hypothesis is that some components of cigarette smoke (e.g.…”

Smoking is associated with increased lesion volumes and brain atrophy in multiple sclerosis

“…Nicotine, a major component of cigarettes, has been shown to increase microvascular blood flow on the brain and to raise the influx of permeable solutes across the blood-brain barrier in rats. 22 This is important because leakage of the blood-brain barrier has been suggested as a factor in initiating the development of MS, and may be relevant to the recent report that cigarette smoking increases the risk of converting from CIS to clinically definite MS. 11 Cigarette smoking causes a transient worsening of motor Table 2 Multiple regression results for MRI measurements with ever-smoker/ never-smoker smoking status correcting for female sex, age, disease and treatment duration, and presence of progressive MS MS ϭ multiple sclerosis; SE ϭ standard error of slope; r p ϭ partial correlation; GMF ϭ gray matter fraction; WMF ϭ white matter fraction; BPF ϭ brain parenchymal fraction; LVV ϭ lateral ventricle volume; 3VW ϭ third ventricle width.…”