Regional blood-brain barrier permeability to water and cerebral blood flow during status epilepticus: Insensitivity to norepinephrine depletion

To test whether status epilepticus alters regional blood-brain barrier (BBB) permeability to water when systemic hypertension is avoided, and whether central noradrenergic innervation contributes to the regulation of BBB in this setting, Wistar rats with unilateral 6-hydroxydopamine lesion of the nucleus locus coeruleus (LC) were subjected to 8 min of bicuculline-induced status epilepticus while ventilated with 100% oxygen; arterial normotension was preserved by withdrawal of arterial blood as required. Regional cerebral blood flow and permeability-times-surface-area product (PS) for water were measured by a double-label modification of the Kety integral strategy, with [ 14C]butanol and [ 3H]water, respectively. In normocapnic control rats, regional cerebral blood flow (rCBF) was 1.92 ± 0.57ml/g/min and water extraction fraction was 0.81 ± 0.08 (S.D.). Values in control rats breathing 100% oxygen were similar. During status epilepticus, rCBF increased two- to three-fold; water extraction fraction declined, but there were no significant side-to-side differences for either rCBF or regional PS product for water in LC-lesioned animals despite an 81% reduction of cortical norepinephrine content on the lesioned side. The PS product for water increased by 42% during status epilepticus, but the flow vs PS-product relationship did not depart from that predicted on the basis of data in control rats. Thus, when systemic hypertension is prevented, brief status epilepticus does not induce abnormal BBB permeability to water, and unilateral LC lesion fails to influence either rCBF or the cerebrovascular PS product for water

Free Fatty Acids and Energy Metabolites in Ischemic Cerebral Cortex with Noradrenaline Depletion

: We tested whether cerebral noradrenaline (NA) may play a central role in mediating the increased production of free fatty acids (FFAs) during cerebral ischemia. Levels of FFAs, cyclic AMP, and NA, as well as ATP, ADP, and AMP, were measured in cerebral cortex during decapitation ischemia in rats 2 weeks after unilateral locus ceruleus lesion. Comparisons were made between the results obtained from the contralateral cortex with normal NA content and the NA‐depleted ipsilateral cortex. Although NA depletion was associated with a diminished transient rise of cyclic AMP in response to ischemia, it failed to influence the magnitude of FFA increase or the decline of energy state within the 15‐min period of ischemia. A more than twofold increase of total FFAs (sum of palmitic, stearic, oleic, arachidonic, and docosahexaenoic acids) was observed in both hemispheres at 1 min after decapitation, when energy failure became manifest. The increased production of FFAs continued throughout the 15 min of ischemia, with a preferential rise in the levels of stearic and arachidonic acids. There was an inverse correlation between FFA levels and total adenylate pool. The results do not support a major role for NA and cyclic AMP in increasing cortical FFAs during complete ischemia. Instead, they are consistent with the view that impaired oxidative phosphorylation activates deacylating enzymes. Disturbance of reacylation due to energy depletion is probably another factor contributing to the continuous increase of FFAs during prolonged ischemia

Ontogeny of the erythroid/HepG2-type glucose transporter (GLUT-1) in the rat nervous system

Central nervous system (CNS) microvessels of adult mammals have an unusually high density of the facilitative glucose transporter GLUT-1. Most systemic microvessels and those of the brain\u27s circumventricular organs, which lack \u27barrier\u27 properties, do not express a high density of GLUT-1. Thus, a high GLUT-1 density is a marker of adult brain endothelium. To determine the stage at which CNS microvessels acquire GLUT-1, we studied by immunocytochemistry GLUT-1 ontogeny in the rat CNS from embryonic day (E) 11 to senescence. At E11, before blood vessels invaded the neuroectodermal tube, GLUT-1 immunoreactivity was already evident in the perineural plexus of vessels and in most of the vascular endothelium of the embryo. GLUT-1 immunoreactivity was also evident in the neuroectoderm. The neuroectoderm gradually lost GLUT-1 expression, and at about E16, GLUT-1 immunoreactivity was no longer detectable in most of the neuroectodermal epithelium, while CNS microvessels had increased their GLUT-1 immunoreactivity. By birth, GLUT-1 immunoreactivity in the CNS was restricted to the endothelium, the epithelium (but not the endothelium) of the choroid plexus, and tanycytes. This cellular distribution of GLUT-1 did not change much between birth and senescence despite considerable postnatal brain development and the increased brain capillary density. Our results suggest that while a CNS factor(s) may not have a role in the induction of the high expression of GLUT-1 in CNS endothelium, such a factor(s) is probably important in maintaining the high level of GLUT-1 in these endothelia. © 1993

Development of Fluorinated 1-.Methyl-4-Phenyl-1 ,2,3,6-. Tetrahydropyridine Analogs with Potent Nigrostriatal Toxicity for Potential Use in Positron Emission Tomography Studies1

ABSTRACT The discovery of 1-methyl-4-phenyl-

Does Endogenous Norepinephrine Regulate Potassium Homeostasis and Metabolism in Rat Cerebral Cortex?

The role of endogenous cerebral norepinephrine (NE) as a modulator of transmembrane cation transport and energy metabolism was evaluated by monitoring extracellular potassium ion activity ([K+]o) in vivo and by measuring cortical Na+,K+-ATPase activity and oxygen consumption in vitro, Ipsilateral cortical NE was depleted by unilateral 6-hydroxydopamine (6-OHDA) lesions of the locus ceruleus (LC). The contralateral cortex was used for control measurements. NE depletion had no effect on resting levels of cortical [K+]o or on the rate of K+ removal from the extracellular space following direct cortical stimulation. There was also no effect of NE depletion on Na+,K+-ATPase activity in cortical homogenates nor on oxygen consumption of cortical slices over a wide range of K+ concentrations. These results indicate that central NE depletion does not influence movements of cortical K+ either directly through an influence on Na+,K+-ATPase activity or indirectly through effects on oxidative metabolism. It is probable, therefore, that previously described effects of NE on cortical oxidative metabolism are mediated through changes in cerebral perfusion and/or modification of substrate availability in vivo