CHANGES IN BRAIN-STEM CALCITONIN-GENE-RELATED PEPTIDE AFTER VIITH ANDVIIITH CRANIAL NERVE LESIONS IN GUINEA-PIG

The present study investigated the effect of seventh and eighth crania l nerve lesions on the prominence of calcitonin gene-related peptide i n the hypoglossal (XII), facial (VII), abducens (VI), and oculomotor ( III) cranial nerve nuclei. Guinea pigs were anesthetized and subjected to unilateral cochlear removal, vestibular end organ ablation, and se venth nerve transection. After a survival period ranging from 4 h to 5 days, each animal was anesthetized and perfused intracardially. Froze n sections were collected through the brainstem and stained immunohist ochemically for calcitonin gene-related peptide using a polyclonal ant ibody with the Vectastain ABC kit and protocol. Positive cells were co unted in each nucleus bilaterally and analyzed for side to side differ ences. Nuclei XII and III showed no significant difference in the numb ers of cells staining positively for calcitonin gene-related peptide b etween the ipsilateral and the contralateral sides to the lesion. Howe ver, nuclei VII and VI showed elevated numbers ipsilateral to the lesi on on some days, but not all. For VII, there was no significant differ ence before 24 h, but there were significant differences 1-5 days afte r the lesion. Similarly, in VI, there was no difference before 24 h, b ut differences were significant beginning with day 1 and continuing th rough day 3, and finally disappearing by day 4. Changes in the numbers of CGRP positive cells in VII measurable 24 h after the lesion and co ntinuing for at least 5 days afterward indicate a central nervous syst em retrograde response to peripheral motor nerve injury. However, sinc e no peripheral damage occurred to any structure other than those rela ted to VII and VIII, increased numbers of calcitonin gene-related pept ide positive cells in VI indicates the presence of a separate mediatin g mechanism. We believe this increase may be due, not to the direct lo ss of a peripheral nerve as in the case of VII, but instead, to an ind irect motor stimulation of the eye muscles (indicated by nystagmus) th at accompanies unilateral vestibular damage. Thus, while the central C GRP response in VII is activated by a retrograde neuronal mechanism, t he central calcitonin gene-related peptide response in VI is activated by an anterograde transsynaptic neuronal mechanism.