Dicyclomine, an M1 muscarinic antagonist, reduces infarct volume in a rat subdural hematoma model.

The rat subdural hematoma (SDH) model produces a zone of ischemic brain damage within the hemisphere beneath the SDH. Previous studies have measured large increases in extracellular acetylcholine during cerebral ischemia in the rat. We examined infarct volume after selectively blocking muscarinic M1 receptors with dicyclomine during SDH. Rats were anesthetized with isoflurane (2%), intubated, and femoral artery and vein cannulated. Autologous blood (0.375 ml) was injected (0.05 ml/min) under the dura of the right parietal cortex. Dicyclomine (5 mg/kg, i.v.) was injected at 5 min after and again at 2 h after completion of the subdural blood infusion. Blood pressure and intracranial pressure (ICP) were continuously measured. At 4 h after SDH rats were euthanized, brains sectioned, and immunoreacted with glia fibrillary acidic protein. Cortical infarct volume was quantified in coronal brain sections at 0.7-mm intervals from +1.0 mm to -3.9 mm relative to bregma. Infarct volume in drug-treated rats (n = 10) 22.1 +/- 6.99 mm3 was significantly smaller (p < 0.02) than vehicle treated rats (n = 10) 56.7 +/- 9.59 mm3. ICP, blood pressure and cerebral perfusion pressure were not significantly different between groups. These data suggest that activation of M1 muscarinic receptors during an ischemic event may contribute to the development of subsequent pathology.