Origin and co-localization of nitric oxide synthase, CGRP, PACAP, and VIP in the cerebral circulation of the rat

Lars Edvinsson, Tor Elsås, Norihiro Suzuki, Toshihiko Shimizu, Tony Jer Fu Lee

Research output: Contribution to journalArticlepeer-review

96 Citations (Scopus)


The origin of perivascular nerve fibres storing nitric oxide synthase (NOS) and co-localisation with perivascular neuropeptides were examined in the rat middle cerebral artery (MCA) by retrograde tracing with True Blue (TB) in combination with immunocytochemistry. Application of TB to the proximal part of the middle cerebral artery labelled nerve cell bodies ipsilaterally in the trigeminal, sphenopalatine, otic, and superior cervical ganglia. A few labelled cell bodies were seen contralaterally, suggesting bilateral innervation. In the parasympathetic sphenopalatine and otic ganglia, numerous TB-labelled cell bodies contained neuronal NOS (C- and N-terminal), vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase activating peptide (PACAP). In the trigeminal ganglion, almost all TB-labelled cell bodies contained calcitonin generelated peptide (CGRP) but only a few cells contained NOS. In the superior cervical ganglion, the majority of the TB-labelled nerve cells contained neuropeptide Y (NPY) but none of them contained NOS. Removal of the ipsilateral sphenopalatine ganglion caused a slight reduction in the number of perivascular VIP-, PACAP-, and NOS-containing fibres after 3 days in the MCA while there was no difference at 2 and 4 weeks after the denervation as compared to control. This indicates that the parasympathetic VIP-, PACAP-, and NOS-immunoreactive nerve fibres in the rat MCA originate from several sources.

Original languageEnglish
Pages (from-to)221-228
Number of pages8
JournalMicroscopy Research and Technique
Issue number3
Publication statusPublished - 2001 May 1
Externally publishedYes


  • Immunocytochemistry
  • Middle cerebral artery
  • Nitric oxide synthase
  • Retrograde tracing
  • True Blue

ASJC Scopus subject areas

  • Anatomy
  • Histology
  • Instrumentation
  • Medical Laboratory Technology


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