Dataset Information

Evidence for CGRP re-uptake in rat dura mater encephali.

ABSTRACT:

Background and purpose

Calcitonin gene-related peptide (CGRP) is widely distributed in the trigeminovascular system and released from sensory fibres of the cranial dura mater upon noxious stimulation. Such release may be a mechanism underlying migraine headache. Based on data from guinea pig basilar artery preparations, we have here studied CGRP release and uptake in an organ preparation of the hemisected rat skull.

Experimental approach

CGRP release from the cranial dura was quantified by a commercial enzyme-linked immunoassay. CGRP was depleted using repetitive challenges of capsaicin. After incubating the tissue with CGRP for 20?min and extensive washing, another capsaicin challenge was performed. Immunohistochemistry was used to visualize CGRP immunofluorescence in dural nerve fibres.

Key results

Capsaicin-induced CGRP release was attenuated by the transient receptor potential vanilloid receptor type I antagonist capsazepine or by Ca(2+)-free solutions. After the CGRP-depleted preparation had been exposed to exogenous CGRP, capsaicin-induced CGRP release was increased compared to the challenge just prior to incubation. CGRP uptake was not influenced by Ca(2+)-free solutions. Olcegepant and CGRP(8-37) (CGRP receptor antagonists) did not affect uptake of CGRP. However, a monoclonal CGRP-binding antibody decreased CGRP uptake significantly. Release of CGRP after incubation was attenuated by Ca(2+)-free solutions and by capsazepine. Immunohistochemical assays indicated a weak trend towards CGRP uptake in rat dura mater.

Conclusion and implications

We have presented evidence for CGRP uptake in nerves and its re-release in rat dura mater. This may have implications for the pathophysiology and treatment of migraine.

SUBMITTER: Gupta S

PROVIDER: S-EPMC3010590 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Publications

Evidence for CGRP re-uptake in rat dura mater encephali.

Gupta Saurabh S Amrutkar Dipak Vasantrao DV Mataji Aydin A Salmasi Hassan H Hay-Schmidt Anders A Sheykhzade Majid M Messlinger Karl K Olesen Jes J Jansen-Olesen Inger I

British journal of pharmacology 20101201 8

<h4>Background and purpose</h4>Calcitonin gene-related peptide (CGRP) is widely distributed in the trigeminovascular system and released from sensory fibres of the cranial dura mater upon noxious stimulation. Such release may be a mechanism underlying migraine headache. Based on data from guinea pig basilar artery preparations, we have here studied CGRP release and uptake in an organ preparation of the hemisected rat skull.<h4>Experimental approach</h4>CGRP release from the cranial dura was quan ...[more]

PMID: 20804493

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Project description:BackgroundDespite greatly renewed interest concerning meningeal lymphatic function over recent years, the lymphatic structures of human dura mater have been less characterized. The available information derives exclusively from autopsy specimens. This study addressed methodological aspects of immunohistochemistry for visualization and characterization of lymphatic vessels in the dura of patients.MethodsDura biopsies were obtained from the right frontal region of the patients with idiopathic normal pressure hydrocephalus (iNPH) who underwent shunt surgery as part of treatment. The dura specimens were prepared using three different methods: Paraformaldehyde (PFA) 4% (Method #1), paraformaldehyde (PFA) 0.5% (Method #2), and freeze-fixation (Method #3). They were further examined with immunohistochemistry using the lymphatic cell marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), and as validation marker we used podoplanin (PDPN).ResultsThe study included 30 iNPH patients who underwent shunt surgery. The dura specimens were obtained average 16.1 ± 4.5 mm lateral to the superior sagittal sinus in the right frontal region (about 12 cm posterior to glabella). While lymphatic structures were seen in 0/7 patients using Method #1, it was found in 4/6 subjects (67%) with Method #2, while in 16/17 subjects (94%) using Method #3. To this end, we characterized three types of meningeal lymphatic vessels: (1) Lymphatic vessels in intimate contact with blood vessels. (2) Lymphatic vessels without nearby blood vessels. (3) Clusters of LYVE-1-expressing cells interspersed with blood vessels. In general, highest density of lymphatic vessels were observed towards the arachnoid membrane rather than towards the skull.ConclusionsThe visualization of meningeal lymphatic vessels in humans seems to be highly sensitive to the tissue processing method. Our observations disclosed most abundant lymphatic vessels towards the arachnoid membrane, and were seen either in close association with blood vessels or remote from blood vessels.

Project description:PurposeSpinal surgery in a previously irradiated field carries increased risk of perioperative complications, such as delayed wound healing or wound infection. In addition, adhesion around the dura mater is often observed clinically. Therefore, similar to radiation-induced fibrosis--a major late-stage radiation injury in other tissue--epidural fibrosis is anticipated to occur after spinal radiation. In this study, we performed histopathologic assessment of postirradiation changes in the spinal dura mater and peridural tissue in mice.Materials and methodsThe thoracolumbar transition of ddY mice was irradiated with a single dose of 10 or 20 Gy. After resection of the irradiated spine, occurrence of epidural fibrosis and expression of transforming growth factor beta 1 in the spinal dura mater were evaluated. In addition, microstructures in the spinal dura mater and peridural tissue were assessed using an electron microscope.ResultsIn the 20-Gy irradiated mice, epidural fibrosis first occurred around 12 weeks postirradiation, and was observed in all cases from 16 weeks postirradiation. In contrast, epidural fibrosis was not observed in the nonirradiated mice. Compared with the nonirradiated mice, the 10- and 20-Gy irradiated mice had significantly more overexpression of transforming growth factor beta 1 at 1 week postirradiation and in the late stages after irradiation. In microstructural assessment, the arachnoid barrier cell layer was thinned at 12 and 24 weeks postirradiation compared with that in the nonirradiated mice.ConclusionIn mice, spinal epidural fibrosis develops in the late stages after high-dose irradiation, and overexpression of transforming growth factor beta 1 occurs in a manner similar to that seen in radiation-induced fibrosis in other tissue. Additionally, thinning of the arachnoid barrier cell layer was observed in the late stages after irradiation. Thus, consideration should be given to the possibility that these phenomena can occur as radiation-induced injuries of the spine.

Dataset Information

Evidence for CGRP re-uptake in rat dura mater encephali.

Background and purpose

Experimental approach

Key results

Conclusion and implications

Publications

Evidence for CGRP re-uptake in rat dura mater encephali.

Similar Datasets

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