title: Verapamil treatment attenuates immunoreactive GFAP at cerebral cortical lesion site.
abstract: Cerebral cortical lesions were produced using a stereotactic injection system in Sprague-Dawley rats randomly assigned to three groups: (1) needle lesioned and uninjected (Lesioned), (2) needle lesion and simultaneous local injection of 50 or 100 microliters 0.9% saline (L/Saline), and (3) needle lesion and simultaneous local injection of 50 or 100 microliters Verapamil-HCl (VHCL) (2.5 mg/ml (5 mM) Abbott Labs, Chicago, IL), a passive, L-type calcium channel blocker (L/VHCL). The lesioning induced expression of glial fibrillary acidic protein (GFAP), a type of intermediate filament protein expressed in reactive astrocytes, at the lesion site. There was a reduction in GFAP-like immunoreactivity (GFAP-IR) in the L/VHCL group versus the Lesioned and the L/Saline groups. There was a five-fold increase of GFAP-IR at 24 h post lesion in the L/Saline group, but no statistically significant increase seen in the Lesioned or L/VHCL groups at either volume. Pretreatment of the anti-GFAP with VHCL did not impair the antigen labeling. To determine whether differences in pHs, or volume could account for these findings, a second experiment was performed using pH-matched saline or VHCL in 10 microliters volume injected into contralateral hemispheres at the time of lesioning. There was an 80% reduction in GFAP-IR in the L/VHCL group at 72 h compared with the L/Saline group. These data suggest that VHCL may suppress the early increase of GFAP-IR in response to cortical lesion and that reducing transmembrane calcium flux through L-type calcium channels may be the mechanism involved.
authors.affiliation: Department of Obstetrics and Gynecology, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: S
authors.initials: S
authors.lastname: Klepper
authors.forename: F
authors.initials: F
authors.lastname: Naftolin
authors.forename: J M
authors.initials: JM
authors.lastname: Piepmeier
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D002121:Calcium Channel Blockers; D005904:Glial Fibrillary Acidic Protein; D014700:Verapamil