Peptidergic innervation of the cerebral circulation. Role in subarachnoid hemorrhage in man
The perivascular fibers, sympathetic fibers (storing noradrenaline, neuropeptide Y), parasympathetic fibers (storing acetylcholine, vasoactive intestinal peptide, peptide histidine methionine and neuropeptide Y) and sensory fibers (storing tachykinins, calcitonin gene-related peptide) were traced using True Blue in monkey.
Tracing studies of the monkey middle-cerebral artery (MCA) innervation confirmed earlier studies in rats and cats, with superior cervical and trigeminal ganglia as main immunostaining areas, and contralateral involvement in the superior cervical and trigeninal ganglia. Sphenopalatine immunostaining was scarce.
The release of neuropeptides in the external jugular vein in humans in the postoperative course after subarachnoid hemorrhage, using radioimmunoassay, was correlated to hemodynamical changes (vasoconstriction) monitored with Doppler ultrasound on middle cerebral (MCA) and internal carotid arteries (ICA).
Neuropeptide Y-like immunoreactivity (NPY-LI) levels were increased compared to controls in patients with hemodynamic changes, and in some patients a relationship was found between velocities and NPY-LI.
Calcitonin gene-related peptide-LI levels were also increased in connection with vasospasm. In patients with MCA lesions a correlation of 0.61, p=0.0002 was found between hemodynamic index (V MCA/V ICA) and CGRP-LI.
The possible sympathetic and trigemino-cerebrovascular activation are discussed.
KeywordsCalcitonin gene-related peptide (CGRP) Doppler Neuropeptide Y (NPY) subarachnoid hemorhage (SAH)
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- Aaslid, R, TM Markwalder, H Nornes: Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 57 (1982) 769–774Google Scholar
- Aaslid, R: Transcranial Dopplersonography. Springer, Wien New York 1986Google Scholar
- Allen, GS, SA Hyo, TJ Freziosi, R Battye, SC Boone, SN Chou, DL Kelly, BK Weir, RA Crabbe, PJ Lavik, SB Rosenbloom, FC Dorsey, CR Ingram, DE Mellits, LA Bertsch, PJ Bolsvert, MB Hundley, RK Johnson, JA Strom, CR Transou: Cerebral arterial spasm — a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med 308 (1983) 619–624Google Scholar
- Arbab, MAR, L Wiklund, N-A Svendgaard: Origin and distribution of cerebral vascular innervation from superior cervical, trigeminal and spinal ganglia investigated with retrograde and anterograde WGA-HRP tracing in the rat. Neurosci 19 (1986) 695–708Google Scholar
- Auer, OM: Acute operation and preventive nimodipine improve outcome in patients with ruptured cerebral aneurysms. Neurosurgery 15 (1984) 57–66Google Scholar
- Brodin, E, LL Peterson, SO Ogren, T Bartfai: Chronic treatment with the serotonin uptake inhibitor zimelidine elevates substance P levels in rat spinal cord. Acta Physiol Scand 122 (1984) 209–211Google Scholar
- Edvinsson, L, JR Copeland, PC Emson, J Mcculloch, R Uddman: Nerve fibers containing neuropeptide Y in the cerebrovascular bed: Immunocytochemistry, radioimmunoassay and vasomotor effects. J Cerebr Blood Flow Metab 7 (1987) 45–57Google Scholar
- Edvinsson, L, H Hara, R Uddman: Retrograde tracing of nerve fibers to the rat middle cerebral artery with True Blue: colocalization with different peptides. J Cerebr Blood Flow Metab 9 (1989) 212–228Google Scholar
- Edvinsson, L, J Mcculloch, R Uddman: Substance P: Immunohistochemical localization and effect upon cat pial arteries in vitro and in situ. J Physiol 325 (1981) 251–258Google Scholar
- Edvinsson, L, J Mcculloch, TA Kingman, R Uddman: Functional significance of the trigeminocerebrovascular innervation: Involvement in the cerebrovascular disorders. In: Rose, FC (ed): Advances in headache research. John Libbey & Co Ltd, UK 1987Google Scholar
- Edvinsson, L, K Nielsen, C Owman, R Sporrong: Cholinergic mechanisms in pial vessels. Histochemistry, electron microscopy and pharmacology. Z Zellforsch 134 (1972) 311–325Google Scholar
- Ekblad, E, L Edvinsson, O Wahlestedt, R Uddman, R Hakanson, F Sundler. Neuropeptide Y coexists and co-operates with noradrenaline in perivascular nerve fibers. Regul Pept 8 (1984) 225–235Google Scholar
- Fisher, CM, JP Kistler, JM Davis: Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 6 (1980) 1–9Google Scholar
- Gilsbach, JM, AG Harders: Morbidity and mortality after early aneurysm surgery — a prospective study with nimodipine prevention. Acta Neurochir 96 (1989) 1–7Google Scholar
- Goadsby, PJ, L Edvinsson, R Ekman: Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol 23 (1988) 193–196Google Scholar
- Grolimund, P, RW Seller: Age dependence of the transcranial Doppler ultrasound study. Ultrasound in Med & Biol 3 (1988) 191–198Google Scholar
- Grunditz, T, R Ekman, R Håkanson: Calcitonin gene-related peptide in thyroid nerve fibers and C cells. Effects on thyroid hormone secretion and response to hypercalcemia. Endocrinology 119 (1986) 1213–2324Google Scholar
- Hara, H, L Edvinsson: Perivascular innervation of the cerebral circulation: involvement in the pathophysiology of subarachnoid hemorrhage. neurosurg Rev 10 (1987) 171–179Google Scholar
- Hara, H, GS Hamill, DM Jacobowitz: Origin of cholinergic nerves to the rat major cerebral arteries: Coexistence with vasoactive intestinal polypeptide. Brain Res Bull 14 (1985) 179–188Google Scholar
- Helm, G, R Ekman, H Rydhstrom, NO Sjoberg, B Walles: Changes in oviductal VIP content induced by sex steroids and inhibitory effect of VIP on spontaneous oviductal contractility. Acta Physiol Scand 125 (1985) 219–224Google Scholar
- Hunt, WE, RM Hess: Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 28 (1968) 14–20Google Scholar
- Jennet, B, M Bond: Assessment of outcome after severe brain damage. A practical scale. Lancet 1 (1975) 480–484Google Scholar
- Juul R, L Edvinsson, TA Fredriksen, R Ekman, AO Brubakk, SE Gisvold: Increased release of neuropeptide Y in the external jugular vein in connection with vasoconstriction following subarachnoid haemorrhage in man. Acta Neurochir. (1990) In pressGoogle Scholar
- Juul, R, L Edvinsson, SE Gisvold, R Ekman, AO Brubakk, TA Fredriksen: Calcitonin gene-related peptide-LI in subarachnoid haemorrhage in man. Signs of activation of the trigemino-cerebrovascular system? Br J Neurosurg 4 (1990) 171–180Google Scholar
- Lindegaard, K-F, P Grolimund, R Aaslid, H Nornes: Evaluation of cerebral AVM s using transcranial Doppler ultrasound. J Neurosurg 65 (1986) 335–344Google Scholar
- Lindegaard, K-F, H Nornes, SJ Bakke, W Sorteberg, P Nakstad: Cerebral vasospasm after subarachnoid haemorrhage investigated by means of transcranial Doppler ultrasound. Acta Neurochir Suppl 42 (1988) 81–84Google Scholar
- Liu-Chen, L-Y, SA Gillespie, TV Norregaard, MA Moskowitz: Co-localization of retrogradely transported wheat germ agglutinin and the putative neurotransmitter substance P within trigeminal ganglion cells projecting to cat middle cerebral artery. J Comp Neurol 225 (1984) 187–192Google Scholar
- Liu-Chen, L-Y, MR Mayberg, MA Moskowitz: Immunohistochemical evidence for a substance P-containing trigeminovascular pathway to pial arteries in cat. Brain Res 268 (1983) 162–166Google Scholar
- Ljunggren, B, L Brandt, H Sæveland, PE Nilsson, S Cronquist, KE Andersson, E Vinge: Outcome in 60 consecutive patients treated with early aneurysm operation and intravenous nimodipine. J Neurosurg 61 (1984) 864–873Google Scholar
- Mayberg, MR, NT Zervas, MA Moskowitz: Trigeminal projections to supratentorial pial and dural blood vessels in cats demonstrated by horseradish peroxidase histochemistry. J Comp Neurol 223 (1984) 46–56Google Scholar
- Mcculloch, J, R Uddman, TA Kingman, L Edvinsson: Calcitonin gene-related peptide: Functional role in cerebrovascular regulation. Proc Natl Acad Sci USA 83 (1986) 5731–5735Google Scholar
- Mendelow, AD: Pathophysiology of delayed ischemic dysfunction after subarachnoid haemorrhage: Experimental and clinical data. Acta Neurochir Suppl 45 (1988) 7–10Google Scholar
- O'Connor, TP, D van der Kooy: Pattern of intracranial and extracranial projections of trigeminal ganglion cells. J Neuroscience 6 (1986) 2200–2207Google Scholar
- Ray, BS, HG Wolff: Experimental studies on headache. Arch Surg 41 (1940) 813–856Google Scholar
- Sawchenko, PE, LW Swanson: A method for tracing biochemically defined pathways in the central nervous system using combined fluorescence retrograde transport and immunohistochemical techniques. Brain Res 210 (1981) 31–51Google Scholar
- Skagerberg, G, A Bjørklund, O Lindvall: Further studies on the use of the fluorescent retrograde tracer True Blue in combination with monoamine histochemistry. J Neurosci Methods 14 (1985) 25–40Google Scholar
- Teasdale, G, B Jennet: Assessment of coma and impaired consciousness. A practical scale. Lancet 2 (1974) 81–84Google Scholar
- Tsai, S-H, S-Z Lin, S-D Wang, S-C Liu, C-J Shih: Retrograde localization of the innervation of the middle cerebral artery with horseradish peroxidase in cats. Neurosurgery 16 (1985) 463–467Google Scholar
- Uddman R, MAR Arbab, L Edvinsson, NA Svendgaard: Origin of nerve fibers to the middle cerebral artery of the squirrel monkey. Retrograde tracing and immunocytochemistry (1990) (in manus)Google Scholar
- Uddman, R, L Edvinsson, R Ekman, T Kingman, J Mcculloch: Innervation of the feline cerebral vasculature by nerve fibers containing calcitonin gene-related peptides: Trigeminal orignin and coexistence with substance P. Neurosci Letters 62 (1985) 131–136Google Scholar
- Uddman R, L Edvinsson: Neuropeptides the cerebral circulation. Cereb Circ Metab Rev in (1989) 230–252Google Scholar
- Walters, BB, SA Gillespie, MA Moskowitz: Cerebrovasular projections from the sphenopalatine and otic ganglia to the middle cerebral artery of the cat. Stroke 17 (1986) 488–494Google Scholar
- Widerløv, E, M Heilig, C Wahlstedt, R Ekman: Possible relationship between neuropeptide Y (NPY) and major depression — evidence from human and animal studies. Nord Psykiatr Tidsskr 42 (1988) 131–137Google Scholar