VERAPAMIL TREATMENT ATTENUATES IMMUNOREACTIVE GFAP AT CEREBRAL CORTICAL LESION SITE

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 simul taneous local injection of 50 or 100 mu l 0.9% saline (L/Saline), and (3) needle lesion and simultaneous local injection of 50 or 100 mu l V erapamil-HCl (VHCL) (2.5 mg/ml (5 mM) Abbott Labs, Chicago, IL), a pas sive, L-type calcium channel blocker (L/VHCL). The lesioning induced e xpression of glial fibrillary acidic protein (GFAP), a type of interme diate filament protein expressed in reactive astrocytes, at the lesion site. There was a reduction in GFAP-Like immunoreactivity (GFAP-IR) i n 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/Salin e group, but no statistically significant increase seen in the Lesione d or L/VHCL groups at either volume. Pretreatment of the anti-GFAP wit h VHCL did not impair the antigen labeling. To determine whether diffe rences in pHs, or volume could account for these findings, a second ex periment was performed using pa-matched saline or VHCL in 10 mu l volu me injected into contralateral hemispheres at the time of lesioning. T here was an 80% reduction in GFAP-IR in the L/VHCL group at 72 h compa red 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 m ay be the mechanism involved.