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Int J Physiol Pathophysiol Pharmacol 2011;3(2):88-96.

Original Article
Zebrafish as an alternative model for hypoxic-ischemic brain damage

Xinge Yu, Yang V. Li

Department of Biomedical Sciences, Program in Biological Sciences, Ohio University, Athens, Ohio 45701, USA

Received March 10, 2011; accepted April 12, 2011; Epub April 20, 2010; Published June 30, 2011

Abstract: Acute cerebral ischemia is one of the leading causes of mortality and chronic disability. Animal models provide an essential
tool for understanding the complex cellular and molecular pathophysiology of hypoxic-ischemia and for testing novel neuroprotective
drugs in the pre-clinical setting. In this study we tested zebrafish as a novel model for hypoxic-ischemic brain damage. We built an
air-proof chamber where water inside had a low oxygen concentration (0.6-0.8 mg/L) proximate to complete hypoxia.  Each zebrafish
was placed individually in the hypoxia chamber and was subjected to hypoxia treatment until it became motionless, lying on its side on
the bottom of the chamber (679.52 ± 90 seconds, mean ± SD, n =23), followed by transferring into a recovery beaker. Overall, 60.87% of
subjects did not recover from hypoxia while 39% survived. The size and distribution of brain injury were determined by
triphenyltetrazolium chloride (TTC) staining. Bilateral, moderate to complete TTC decoloration or demarcation of the infarct after 10
minutes of hypoxic treatment was clearly visible in the optic tectum of the optic lobe. The size of the infarct expanded to the deep
structure of the optic lobe with longer hypoxic treatments. The zebrafish that survived hypoxia experienced initial twitching followed by
unbalanced erratic movements until they regained coordinated, balanced swimming ability. These data indicate that zebrafish are
susceptible to hypoxic attack and suggest that the model we present in this study can be used as an alternative model to evaluate
hypoxia-induced brain damage. (IJPPP1103001).

Key words: Ischemia, zebrafish, animal model, stroke, brain injury, triphenyltetrazolium

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Address all correspondence to:
Yang V. Li, PhD
346 Irvine Hall, Ohio University
Athens, OH, 45701, USA.
Fax: 740-593-2389