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Inhibition of Carbonic Anhydrase Reduces Brain Injury After Intracerebral Hemorrhage

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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 h 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 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.

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Acknowledgments

This study was supported by grants NS-017760, NS-039866, and NS-057539 from the National Institutes of Health (NIH) and 0840016N from the American Heart Association (AHA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH and AHA.

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  1. R5018 Biomedical Science Research Building, Department of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA

    Fuyou Guo, Ya Hua, Jinhu Wang, Richard F. Keep & Guohua Xi

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  1. Fuyou Guo
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  2. Ya Hua
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Correspondence to Guohua Xi.

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Guo, F., Hua, Y., Wang, J. et al. Inhibition of Carbonic Anhydrase Reduces Brain Injury After Intracerebral Hemorrhage. Transl. Stroke Res. 3, 130–137 (2012). https://doi.org/10.1007/s12975-011-0106-0

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