Central noradrenergic regulation of cerebral blood flow and vascular permeability.

Abstract

Anatomical studies employing the immu- MATERIALS AND METHODS Four adult rhesus monkeys (Macaca mulatta) were used for this study. Four weeks prior to experimentation they were anesthetized with phencyclidine (2 mg/kg) and the right external carotid artery was ligated at its origin to facilitate the injection of '50-labeled water into the internal carotid artery. At the same time, three of the monkeys underwent bilateral superior cervical ganglionectomies. The tissue removed was examined histologically to confirm its identity as sympathetic ganglion.In order to administer drugs that might directly affect the central noradrenergic system, two cannulae systems were stereotaxically implanted 3 weeks prior to experimentation under phencyclidine anesthesia (2 mg/kg). Twenty-three gauge stainless steel permanent guide cannulae were placed in each lateral ventricle in all four animals. These cannulae served to administer drugs intended to affect noradrenergic fibers or terminals. In two of the monkeys (both ganglionectomized) a second set set of guide cannulae was bilaterally implanted in a position directly dorsal to the rostral third of the locus coeruleus. These guide cannulae permitted the placement of 30-gauge injection cannulae at the time of the experiment which extended below the tip of the guide cannulae into the locus coeruleus.At the time of the experiment the monkeys were anesthetized with phencyclidine (2 mg/kg), paralyzed with gallamine, and passively ventilated on 100% oxygen. The end-tidal CO2 pressure (PCo2), arterial blood pressure, and rectal temperature were continuously monitored. Rectal temperature was maintained between 370 and 390 with a heating pad. Arterial pH, and arterial CO2 and 02 pressure (Paco2, and PaO2, respectively) were measured before and after each series of isotope injections.The time course of '50-labeled water through the brain was detected by a 3 X 2 inch sodium iodide, thallium-impregnated scintillation detector appropriately positioned and collimated to insure uniform detection efficiency. The signal from the detector was processed in a manner previously described (4). Radioactive water labeled with l5O (half-life 123 sec) was produced for these studies in the Washington University Medical School Cyclotron by deuteron bombardment of nitrogen gas (5).The extraction fraction of labeled water (E) was obtained by graphically extrapolating the 25-60 sec nearly linear interval of the semilogarithmic plot of tissue water clearance (B, Fig. 1) back to the abscissa of the maximum perfusion peak (A, Fig. 1) and computing the ratio E = B/A.Mean CBF was determined by the height/area residue detection method from the injected bolus of labeled water (4,6). This method requires monitoring of the brain residue 3726

Catecholaminergic Control of Mitogen-Activated Protein Kinase Signaling in Paraventricular Neuroendocrine NeuronsIn VivoandIn Vitro: A Proposed Role during Glycemic Challenges

“…At present, it is unclear whether this staining represents specific phospho-ERK1/2 labeling and whether such staining is altered significantly by NE treatment. We note this staining here, however, because (1) there is at least one report documenting phospho-ERK1/2 staining on endothelial-like cells of blood vessels in brain tissue (Nadjar et al, 2005); (2) both phospho-ERK1/2 (Armstead, 2006) and NE (Raichle et al, 1975;Mulligan and MacVicar, 2004) have similarly directed vasoconstrictor actions on cerebral microvasculature; and (3) central noradrenergic fibers directly innervate blood vessels of the PVH (Swanson et al, 1977) and cortex (Cohen et al, 1997).…”

Functional neuroimaging of normal human sleep by positron emission tomography

“…LC stimulation was shown to decrease CBF, together with cerebral metabolism (Raichle et al 1975;Abraham et al 1979;Goadsby et al 1982;Buchweitz et al 1985), whereas LC lesions by electrolysis or 6-hydroxydopamine have provided controversial results: an increase in CBF (Bates et al 1977) or the absence of any CBF change (Dahlgren et al 1981b 2 ;Reddy et al 1986). Results concerning the vasomotor in¯uence of RN are also controversial.…”

Assessment of the permeability of the blood-retinal barrier in hypertensive rats.

“…20 The effect of the catecholaminergic nerves from the locus ceruleus is unclear but may influence capillary permeability. 21 Unlike cerebral blood vessels, the retinal blood vessels do not have a sympathetic nerve supply. 22 -M The retinal circulation is controlled by changes in pressure in the ophthalmic artery, which does have a sympathetic innervation, as well as by humoral and local factors.…”