Inhibition of Carbonic Anhydrase Reduces Brain Injury After Intracerebral Hemorrhage

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 mu l 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 mu l CA-1 (1 mu g/mu l) or saline. Brain water content, microglia activation, and neuronal death (Fluoro-Jade C staining) were examined 24 h later. In the third group, acetazolamide (AZA, 5 mu l, 1 mM), an inhibitor of carbonic anhydrases, or vehicle was co-injected with 100 mu l 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 h after ICH. Intracaudate injection of CA-1 induced brain edema (79.0 +/- 0.6 vs. 78.0 +/- 0.2% in the saline group, p<0.01), microglia activation, and neuronal death (p<0.01) at 24 h. 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.