Elsevier

Neuroscience

Volume 48, Issue 1, May 1992, Pages 187-203
Neuroscience

Ultrastructural evidence for neurogenically mediated changes in blood vessels of the rat dura mater and tongue following antidromic trigeminal stimulation

https://doi.org/10.1016/0306-4522(92)90348-6Get rights and content

Abstract

We investigated the effects of unilateral electrical trigeminal ganglion stimulation (0.1 or 1.0 mA, 5 Hz, 5 ms, 5 min) on the morphology of blood vessels within the rat dura mater and tongue using light and transmission electron microscopy. Stimulation at both intensities caused changes which were confined to the ipsilateral post-capillary venules except in the tongue where arterioles were affected as well. Changes were more marked after 1.0mA. Dramatic increases in the numbers of endothelial pinocytotic vesicles were found along the luminal and abluminal surfaces ipsilateral to the stimulation. Tight junctions remained largely intact, except that injected ferritin particles were occasionally trapped inside these junctions. Cytoplasmic microvilli and endothelial blebs were sometimes present as well. Approximately 80% of the examined dural post-capillary venules showed one or more of these endothelial changes. Horseradish peroxidase injected intravenously 5 min prior to stimulation was detected in the extracellular space surrounding dural blood vessels and within pinocytotic vesicles. Ferritin injected similarly, was also localized in post-capillary venule walls, interstitial spaces, intraendothelial vesicles and in vacuoles. Platelet accumulation and aggregation were present in approximately 10% of post-capillary venules in dura and tongue. These changes were associated with mast cell secretion, but neither vascular nor mast cell activation was observed in adult rats in whom C-fibers were destroyed during the neonatal period with capsaicin.

The present observations provide morphological evidence which supports findings from previously reported albumin tracer studies suggesting enhanced transport and endothelial activation following electrical stimulation of small caliber afferent fibers.

References (98)

  • TaniE. et al.

    Histamine application to the nasal mucosa induces release of CGRP and SP from peripheral terminals of trigeminal ganglion: a morphological study in the guinea pig

    Neurosci. Lett.

    (1990)
  • AndresK.H. et al.

    Nerve fibers and their terminals of the dura mater encephali of the rat

    Anat. Embryol., Berlin

    (1987)
  • AnthonyM.

    The mechanisms underlying migraine

    Med. J. Aust.

    (1972)
  • AnthonyM. et al.

    The possible relationship of serotonin to the migraine syndrome

  • AnthonyM. et al.

    The role of serotonin in migraine

  • ArnauxB. et al.

    Release of platelet-activating factor (PAF-acether) from alveolar macrophages by the calcium ionophore A23187 and phagocytosis

    Eur. J. clin. Invest.

    (1980)
  • Arsenio-NunesM.L. et al.

    Ultrastructural and histochemical investigation of the cerebral cortex of cat during and after complete ischemia

    Acta neuropath., Berlin

    (1973)
  • BalinB.J. et al.

    Tubulae profiles do not form transendothelial channels through the blood-brain barrier

    J. Neurocytol.

    (1987)
  • BienenstockJ. et al.

    Evidence for mast cell-nerve interactions

  • BienenstockJ. et al.

    The role of mast cells in inflammatory processes: evidence for nerve mast cell interactions

    Int. Archs Allergy appl. Immunol.

    (1987)
  • BottomleyJ.M. et al.

    Platelet lipid composition in human migraine

    Headache

    (1982)
  • BrainS.D. et al.

    Calcitonin gene-related peptide is a potent vasodilator

    Nature

    (1985)
  • BroadwellR.D.

    Trancytosis of macromolecules through the blood-brain barrier: a cell biological perspective and critical appraisal

    Acta neuropath., Berlin

    (1989)
  • BuzziM.G. et al.

    Dihydroergotamine and sumatriptan attenuate the increase in plasma CGRP levels within rat superior sagittal sinus during electrical trigeminal ganglion stimulation

    Neuropharmacology

    (1992)
  • BuzziM.G. et al.

    5-HT1 receptor agonists for the treatment of migraine block mast cell, endothelial and platelet activation within the dura mater after trigeminal stimulation

    Brain Res.

    (1991)
  • BuzziM.G. et al.

    The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater

    Br. J. Pharmac.

    (1990)
  • BuzziM.G. et al.

    Indomethacin and acetylsalicylic acid block plasma protein extravasation in rat dura mater following electrical stimulation of the rat trigeminal ganglia

    Eur. J. Pharmac.

    (1989)
  • CamussiG. et al.

    The release of platelet-activating factor from human endothelial cells in culture

    J. Immunol.

    (1983)
  • ChevilleN.F.

    Inflammation and repair

  • ChiangJ. et al.

    Cerebral ischemia III. Vascular changes

    Am. J. Path.

    (1968)
  • ChignardM. et al.

    Formation of PAF-acether and of another aggregating phospholipid by human platelets

  • CouchJ.R. et al.

    Platelet aggregability in migraine

    Neurology

    (1977)
  • CoutureR. et al.

    Studies on the trigeminal antidromic vasodilation and plasma extravasation in the rat

    J. Physiol.

    (1984)
  • Dalsgaard-NielsenT. et al.

    Serotonin release and uptake in platelets from healthy persons and migrainous patients in attack-free intervals

    Headache

    (1974)
  • DietrichW.D. et al.

    Cerebral endothelial microvillus formation following global forebrain ischemia

    J. Neuropath. exp. Neurol.

    (1989)
  • DimitriadouV. et al.

    Trigeminal sensory fiber stimulation induces morphologic changes reflecting secretion in rat dura mast cells

    Neuroscience

    (1991)
  • EdvinssonL. et al.

    Substance P: localization, concentration and release in cerebral arteries, choroid plexus and dura mater

    Cell Tiss. Res.

    (1983)
  • ErjavecF. et al.

    Release of histamine by substance P

    Naunyn-Schmiedeberg's Arch. Pharmac.

    (1981)
  • FewtrellC.M. et al.

    The effects of substance P on histamine and 5-hydroxytryptamine release in the rat

    J. Physiol.

    (1982)
  • ForemanJ. et al.

    Histamine release and vascular changes induced by neuropeptides

    Agents Actions

    (1983)
  • GalliganJ.J. et al.

    Substance P mediates neurogenic vasodilation in extrinsically denervated guinea-pig submucosal arterioles

    J. Physiol.

    (1990)
  • GawelM.J. et al.

    The platelet release reaction during migraine attacks

    Headache

    (1979)
  • GoadsbyP.J. et al.

    Release of vasoactive peptides in the extracerebral circulation of man and the cat during activation of the trigeminovascular system

    Ann. Neurol.

    (1988)
  • GrahamR.C. et al.

    The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique

    J. Histochem. Cytochem.

    (1966)
  • HazamaF. et al.

    Pathological changes of cerebral vessel endothelial cells in spontaneously hypertensive rats, with special reference to the role of the cells in the development of hypertensive cerebrovascular lesions

  • HazamaF. et al.

    Scanning electron microscopic study of endothelial cells of cerebral arteries from spontaneously hypertensive rats

    Stroke

    (1979)
  • HeineH. et al.

    Relationships between mast cells and preterminal nerve fibers

    Z. mikrosk.-anat. Forsch.

    (1975)
  • HiltonB.P. et al.

    5-Hydroxytryptamine levels and platelet aggregation responses in subjects with acute migraine headache

    J. Neurol. Neurosurg. Psychiat.

    (1972)
  • HornstraG.

    Platelet-vessel wall interaction: role of blood clotting

    Phil. Trans. R. Soc., Lond. (Biol.)

    (1981)
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