Time course of variations in rabbit cerebrospinal fluid levels of calcitonin gene-related peptide- and substance P-like immunoreactivity in experimental subarachnoid hemorrhage.
OBJECTIVE
Cerebral vasospasm after subarachnoid hemorrhage may result partially from the imbalance between vasodilator and vasoconstrictor factors. The vasodilator peptides substance P and calcitonin gene-related peptide contained in the trigeminovascular system are involved in the vasomotor phenomenon occurring after subarachnoid hemorrhage. The delayed arterial narrowing may reflect the time course of the release of these peptides. Therefore, we followed the time course of the changes in cerebrospinal fluid immunoreactivity of substance P and calcitonin gene-related peptide in a model of experimental subarachnoid hemorrhage.


METHODS
Cerebrospinal fluid samples were taken in the basal state and at 30 minutes, 24 hours, and 3 days after a single injection of 1 mL autologous arterial blood into the cisterna magna of rabbits using a percutaneous suboccipital route. Substance P-like and calcitonin gene-related peptide-like immunoreactivities were determined in centrifuged cerebrospinal fluid and plasma by use of enzyme immunoassay.


RESULTS
Early (30 minutes) after induced subarachnoid hemorrhage, there was a large increase in cerebrospinal fluid substance P-like immunoreactivity (P < .01) and calcitonin gene-related peptide-like immunoreactivity (P < .01). Arterial and hemorrhagic cerebrospinal fluid levels of substance P-like immunoreactivity were different (P < .03), indicating that the increased cerebrospinal fluid level did not result only from the blood contamination. Twenty-four hours after induced subarachnoid hemorrhage, the immunoreactivities of substance P and calcitonin gene-related peptide remained significantly higher than the basal level (P < .01). At day 3, both immunoreactivities had decreased to a level nonsignificantly different from the basal level.


CONCLUSIONS
The early high values of the cerebrospinal fluid immunoreactivities for substance P and calcitonin gene-related peptide, apart from the contamination by arterial blood, probably resulted from the depletion of neurotransmitter peptides from the trigeminovascular fibers.
Tran Dinh
Y R
YR
Laboratoire de Recherches Cérébrovasculaires, CNRS UA 641, Faculté de Médecine, Université Paris VII, France.
Debdi
M
M
Couraud
J Y
JY
Creminon
C
C
Seylaz
J
J
Sercombe
R
R
D000818:Animals; D002116:Calcitonin / Q000134:cerebrospinal fluid*; D007124:Immunoenzyme Techniques; D008297:Male; D009994:Osmolar Concentration; D011817:Rabbits; D012016:Reference Values; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid*; D013373:Substance P / Q000134:cerebrospinal fluid*; D013997:Time Factors
D013373:Substance P; D002116:Calcitonin