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Journal of Neurosurgical Sciences 2000 December;44(4):186-91

Copyright © 2000 EDIZIONI MINERVA MEDICA

language: English

The importance of substance P and calcitonin gene related peptide as vasodilator neuropeptide during acute phase of experimental posthemorrhagic vasospasm

Locatelli M.

Department of Neurosugery, University of Milan, Ospedale Maggiore di Milano, Policlinico IRCCS, Milan, Italy


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Background. Several immu­no­his­to­chem­i­cal stud­ies con­duct­ed in the ­acute ­phase fol­low­ing SAH ­have dem­on­strat­ed a ­marked deple­tion of cer­tain pep­tides ­like Substance P (SP), Calcitonin Gene Related Peptide (CGRP) ­from the adven­ti­tia of per­i­vas­cu­lar ­nerves. The ­present experi­men­tal ­study was car­ried out ­with the aim of deter­min­ing wheth­er the deple­tion of ­these pep­tides ­could be a pro­tec­tion mech­a­nism ­against the fac­tors ­which sus­tain the vasos­pasm.
Methods. To accom­plish ­this ­goal, we admin­is­tered spe­cif­ic anti­ser­um to ­block the poten­tial ­effect of neu­ro­pep­tides (SP and ­CGRP) ­prior to SAH. Our ­study ­tried ­also to real­ize wheth­er dif­fer­ence can be dem­on­strat­ed ­between endo­the­li­um-depen­dent (SP) and endo­the­li­um- inde­pen­dent vas­o­dil­a­to­ry mech­a­nisms (­CGRP) dur­ing the ­acute ­phase of vasos­pasm. Twenty-­three rab­bits ­were divid­ed in 5 experi­men­tal ­groups: Group A includ­ed nor­mal con­trol ani­mals, Group B includ­ed rab­bits who ­received ­saline injec­tion ­prior to SAH, Group C includ­ed ani­mals who ­received pre­im­mune ser­um, ­groups D and E includ­ed ani­mals who ­received respec­tive­ly anti­ser­um ­against ­CGRP and ­against SP ­prior to SAH. The anti­se­ra ­were admin­is­tered ­into the cis­ter­na mag­na by ­means of per­cut­ane­ous sub­oc­cip­i­tal punc­ture. After 15 min­utes 1 ml of autol­o­gous non-hep­a­ri­nized ­blood was inject­ed in the ­same way. After 20 min­utes the ani­mals ­were sac­ri­ficed by car­diac per­fu­sion. The bas­i­lar ­artery was ­removed by ­means of trans­cli­val ­approach and it was includ­ed in Epon 812. Mean diam­e­ters and lumi­nal are­as of the arter­ies ­were measured ­with mor­pho­met­ric meth­od on sec­tions of 2-3 µm of thick­ness.
Results. The ­results ­showed a ­reduced ­mean diam­e­ter and lumi­nal are­as in the ­group B com­par­ing to nor­mal con­trols of the ­group A. A ­marked vasos­pasm is main­ly evi­dent in ­group D and E. In ­group C the vasos­pasm is not sig­nif­i­cant­ly dif­fer­ent ­from ­that of ­group B. No sig­nif­i­cant dif­fer­ence was dem­on­strat­ed ­between ­group D and ­group E.
Conclusions. We can con­clude ­that: 1) the ­marked deple­tion of neu­ro­pep­tides in the ear­ly phas­es of vasos­pasm rep­re­sents a func­tion­al phe­nom­e­non in ­order to ­reduce the effec­tive­ness of spas­mo­gen­ic sti­mu­la. In ­fact the inhi­bi­tion of the activ­ity of ­these neu­ro­pep­tides wors­es the ­entity of the vasos­pasm. 2) During the ­acute ­phase of vasos­pasm the endo­the­li­um-depen­dent vas­o­dil­a­to­ry mech­a­nism is ­still func­tion­ing. No sig­nif­i­cant dif­fer­ence in the ­entity of vasos­pasm has ­been dem­on­strat­ed ­between inhi­bi­tion of SP (endo­the­li­um-depen­dent) and ­CGRP (endo­the­li­um-inde­pen­dent). Inactivation of ­such a mech­a­nism ­occurs dur­ing ­late phas­es.

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