Innervation and Effects of Dilatory Neuropeptides on Cerebral Vessels

Edvinsson, Lars

doi:10.1159/000158841

Cited by 34 publications

(34 citation statements)

References 45 publications

(71 reference statements)

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“…The basic function of CGRP in the pathomechanism of migraine was proposed more than two decades ago (Edvinsson, 1991). Human CGRP has two isoforms: α-CGRP and β-CGRP (Emeson et al, 1989;Tippins et al, 1986).…”

Section: Cgrpmentioning

confidence: 99%

Migraine and neuropeptides

et al. 2015

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Section: Cgrpmentioning

confidence: 99%

Migraine and neuropeptides

et al. 2015

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“…In a rabbit model of pneumococcal meningitis, elevated concentrations of glutamate were detected in the CSF 22 hours after infec tion (Guerra-Romero et aI., 1993), indicating an in creased release of glutamate during the course of the intlammation. Substance P, which is released by perivas cular nerves originating from the trigeminal ganglion (Edvinsson, 1991), induces dilation of pial arterioles (Edvinsson et aI., 1981). A previous study using the same rat model as in the current study showed that the sub stance P antagonist spantide was able to prevent pial arteriolar vasodilation in the early phase of experimental pneumococcal meningitis (Pfister et aI., 1995).…”

Section: Discussionmentioning

confidence: 99%

7-Nitroindazole Inhibits Pial Arteriolar Vasodilation in a Rat Model of Pneumococcal Meningitis

Paul

Koedel

Pfister

1997

J Cereb Blood Flow Metab

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Summary: This study investigates how the neuronal and in ducible nitric oxide synthase (NOS) pathways contribute to the cerebrovascular changes in the early phase of experimental pneumococcal meningitis in rats. Using a closed cranial win dow preparation, the diameters of pial arterioles were measured during 4 hours after intracisternal injection of heat-killed pneu mococci and compared with controls (n = 6). Injection of pneumococci (n = 7) caused a significant increase in pial arteriolar diameter (157 ± 22% after 4 hours; P < 0.05, com pared with 104 ± II % in controls), intracranial pressure, CSF white blood cell counts, and brain water content. Treatment with the neuronal NOS inhibitor 7-nitroindazole (50 mg/kg given intraperitoneally, n = 5) prevented pneumococci induced vasodilation (l07 ± 20% at 4 hours), whereas S methylisothiourea (SMT; 0. I mg/kg given intraperitoneally, Bacterial meningitis in adults still is a serious disease. Mortality rates for pneumococcal meningitis are still as high as 20% to 30% (Berkowitz, 1993; Durand et ai, 1993; Pfister et aI., 1993). Major complications during the course of the disease include brain edema, increased intracranial pressure (lCP) , and cerebrovascular alter ations (e.g., focal cortical hyperperfusion, arterial steno sis and spasms), as well as septic sinus venous throm bosis (Pfister et aI., 1992). Pial arteriolar vasodilation and an increase in cerebral blood flow are found in early stages of experimental bacterial meningitis (Pfister et aI., 1990; Berkowitz et aI., 1993), whereas a reduced cereReceived July 31 , 1996; final revision received February 12, 1997: accepted April 10, 1997.This study was supported by grants from the Deutsche Forschungs gemeinschaft (Project Pf 246/5-1 to R-W. Pfister).Address correspondence and reprint requests to Dr. Hans-Walter Pfister, Department of Neurology, Klinikurn Gro13hadern, Ludwig Maximilians-University Miinchen, Marchioninistr. 15, 81377 Munich, Germany.Ahhreviations used: CSF-WBC, cerebrospinal fluid white blood cell; ICP, intracranial pressure; 7-NI, 7-nitroindazole; NO, nitric oxide; NOS, nitric oxide synthase; eNOS, endothelial isoform of nitric oxide; nNOS, constitutive neuronal isoform of nitric oxide; iNOS, inducible isoform of nitric oxide; PBS, phosphate-buffered saline; SMT, S mcthylisothiourea.985 n = 5), which predominantly inhibits the inducible NOS, did not influence pneumococci-induced vasodilation (154 ± 38% at 4 hours). S-methylisothiourea at a dose of 1.0 mg/kg (n = 5), attenuated the vasodilation (124 ± 18% at 4 hours). However, the increase in mean arterial blood pressure after SMT at 1.0 mg/kg, but not at 0. I mg/kg, suggests that the higher dose of SMT influenced the constitutive NOS activity, causing inhibi tion of the pneumococci-induced vasodilation. Neither SMT (at both doses) nor 7-nitroindazole influenced the increase in brain water content, intracranial pressure, and CSF white blood cell counts in pneumococci-challenged rats. Our study suggests that pial arteriolar vasodilation in the e...

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“…With regard to the pathogenesis of headache, the meninges and the intracranial vessels are of particular interest (Moskowitz et al 1989;Edvinsson 1991). Ray and Wolff (1940) demonstrated pain-sensitive regions in the dura and at the circulus arteriosus during mechanical, chemical, or faradic stimulation.…”

Section: Introductionmentioning

confidence: 99%

Topography and immunocytochemical characterization of nerve fibers in the leptomeningeal compartments of the rat. A light- and electron-microscopical study

Fricke

Düring

Andres

1996

Cell and Tissue Research

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The localization of peptidergic, catecholaminergic, and nitroxidergic nerve fibers in the ventral leptomeningeal connective tissue compartment was studied in whole-mount preparations and serial semithin and ultrathin sections. For immunocytochemistry, whole-mount preparations of the leptomeninges and ventral brain slices with the meninges were incubated as free-floating specimens with primary antibodies against protein gene product 9.5 (PGP 9.5), substance P (SP), calcitonin gene-related peptide (CGRP), dopamine beta-hydroxylase (DbetaH), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and nitric oxide synthase (NOS) using the avidin-biotin-peroxidase method. Based on the regional differences of the connective tissue organization, the leptomeninx is subdivided into the pial, trabecular, and adventitial leptomeninx. The antibody PGP 9.5 stains all unmyelinated nerve fibers in the leptomeninx. Although the highest density of nerve fibers occurs in the adventitial leptomeninx, nerve fibers, and terminals are additionally present in the trabecular and pial leptomeninx. DbetaH-, NPY-, VIP- and NOS-immunoreactive (IR) nerve fibers occur exclusively in the adventitial leptomeninx forming neuromuscular junctions. CGRP- and SP-IR nerve fibers are localized in all three leptomeningeal compartments where they terminate close to the subarachnoid space (type 1) or within the connective tissue (type 2). Due to their morphological and immunocytochemical characterization a possible chemo-, mechano- or nociceptive function is discussed in the context of pathophysiological aspects.

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Innervation and Effects of Dilatory Neuropeptides on Cerebral Vessels

Cited by 34 publications

References 45 publications

Migraine and neuropeptides

Migraine and neuropeptides

7-Nitroindazole Inhibits Pial Arteriolar Vasodilation in a Rat Model of Pneumococcal Meningitis

Topography and immunocytochemical characterization of nerve fibers in the leptomeningeal compartments of the rat. A light- and electron-microscopical study

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