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

lingua: Inglese

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


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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