Time Course of Variations in Rabbit Cerebrospinal Fluid Levels of Calcitonin Gene-Related Peptide- and Substance P-Like Immunoreactivity in Experimental Subarachnoid Hemorrhage

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Abstract

Background and Purpose

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 generelated peptide, apart from the contamination by arterial blood, probably resulted from the depletion of neurotransmitter peptides from the trigeminovascular fibers.

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