title: Inhibition of carbonic anhydrase reduces brain injury after intracerebral hemorrhage.
abstract: Carbonic anhydrase-1 (CA-1) is a metalloenzyme present at high concentrations in erythrocytes. Our previous studies showed that erythrocyte lysis contributes to brain edema formation after intracerebral hemorrhage (ICH) and a recent study indicates that CA-1 can cause blood-brain barrier disruption. The present study investigated the role of CA-1 in ICH-induced brain injury.There were three groups in the study. In the first, adult male Sprague-Dawley rats received 100 μl autologous blood injection into the right caudate. Sham rats had a needle insertion. Rat brains were used for brain CA-1 level determination. In the second group, rats received an intracaudate injection of either 50 μl CA-1 (1 μg/μl) or saline. Brain water content, microglia activation and neuronal death (Fluoro-Jade C staining) were examined 24 hours later. In the third group, acetazolamide (AZA, 5 μl, 1 mM), an inhibitor of carbonic anhydrases, or vehicle was co-injected with 100 μl blood. Brain water content, neuronal death and behavioral deficits were measured. We found that CA-I levels were elevated in the ipsilateral basal ganglia at 24 hours after ICH. Intracaudate injection of CA-1 induced brain edema (79.0 ± 0.6 vs. 78.0±0.2% in saline group, p<0.01), microglia activation and neuronal death (p<0.01) at 24 hours. AZA, an inhibitor of CA, reduced ICH-induced brain water content (79.3 ± 0.7 vs. 81.0 ± 1.0% in the vehicle-treated group, p<0.05), neuronal death and improved functional outcome (p<0.05).These results suggest that CA-1 from erythrocyte lysis contributes to brain injury after ICH.
authors.affiliation: Department of Neurosurgery, University of Michigan.
authors.forename: Fuyou
authors.initials: F
authors.lastname: Guo
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
authors.forename: Jinhu
authors.initials: J
authors.lastname: Wang
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi