Adrenergic-Induced Enhancement of Brain Barrier System Permeability to Small Nonelectrolytes: Choroid Plexus versus Cerebral Capillaries

Abstract

Summary: Acute hypertension induced by adrenergic agents opens up the blood-CSF barrier (choroid plexus) to nonelectrolyte and protein tracers. Sprague-Dawley adult rats anesthetized with ketamine were given an in travenous bolus of either epinephrine (10 f,Lg/kg), phen ylephrine (100 f,Lg/kg), isoproterenol (10 f,Lg/kg), or D,L amphetamine (2 mg/kg). Tr acers were injected simulta neously with test agents, and the animals killed 10 min later. Epinephrine raised MABP by 57 mm Hg, to a peak pressure of 160 mm Hg; and it increased the volume of distribution (Vd) of urea, mannitol, and 125I-bovine serum albumin in CSF by l.5-, 2.7-, and 30-fold, respectively.There was enhanced uptake by lateral and fourth ven tricle choroid plexuses, cerebral cortex, cerebellum, me dulla, and thalamus. Phenylephrine also elevated MABP to 160 mm Hg, but it increased permeation of tracers into CSF (and several brain regions) to a lesser extent than Adrenergic agonists that raise blood pressure can open the blood-brain barrier (BBB) to large mole cules such as albumin and horseradish peroxidase and to smaller molecules like inulin and norepi nephrine (Johansson, 1980). Metaraminol, epineph rine, amphetamine, norepinephrine, and phenyl ephrine increase BBB permeability, but if the agent induced rise in blood pressure is blocked, no change in tracer permeation is observed (Johansson, 1980). A rise in intracarotid pressure concurrent with sys temic hypervolemia also opens the BBB (Nagy et aI., 1979). Augmented penetration of isotopes with adrenergic agonists is related to the rate and extent of blood pressure rise and to the size of the cerebral vessel lumen; vasoconstriction generally decreases

Homeostatic capabilities of the choroid plexus epithelium in Alzheimer's disease

“…When neurodegenerative diseases, ischemia [27,28] and elevated pressure [29,30] inflict damage on the choroidal epithelium, there are resultant adverse changes in CSF composition and volume. Because neurons are sensitive to instabilities in CSF dynamics and constituents, it is important to assess the nature and progression of disrupted CP function in chronic diseases.…”

The Distributional Nexus of Choroid Plexus to Cerebrospinal Fluid, Ependyma and Brain

“…All in all, the vacuolation phenomena in CP suggest the increased passage of pathogenic molecules into CSF, and then from ventricles into the brain. Strengthening of this postulate comes from similar observations in several other models of BCSFB breakdown: protein penetration into CSF, ventriculomegaly, ependymal damage, and periventricular edema (H. S. Sharma, Duncan, and Johanson 2006;Murphy and Johanson 1985).…”

“…Collapse of CP-CSF results from many stresses on CNS: arterial hypertension (Murphy and Johanson 1985), transient forebrain ischemia (Palm et al 1995 (Preston 2001). Upon BCSFB damage in pathophysiologic states, the increased paracellular permeability allows accession of plasma proteins and other markers to CSF.…”

Amphetamine- and methamphetamine-induced hyperthermia: Implications of the effects produced in brain vasculature and peripheral organs to forebrain neurotoxicity

“…Differences seen between the physiological effects of AMPH in our study with those reported in the earlier study, may explain the greater adverse effects. That is, more prolonged neurotoxic exposure to AMPH produced both severe hyperthermia and hypertension which was not observed in the earlier study with a single dose of AMPH 98 . In addition, adverse effects produced by hyperthermia alone (EIH) are likely as great, or greater, than AMPH 43 .…”