The effects of the halogenated aromatic amino acid 3,5-dibromo-D-tyrosine (3,5-DBr-D-Tyr) were studied in rat models of stroke and epileptic seizures caused by middle cerebral artery occlusion (MCAo) through respective intracerebral injection of endothelin-1 (ET-1) and intraperitoneal (i.p.) injection of pentylenetetrazole (PTZ). 3,5-DBr-D-Tyr was administered as three bolus injections (30 or 90 mg/kg, i.p.) starting at 30, 90, and 180 min after ET-1 administration or as a single bolus (30 mg/kg, i.p.) 15 min prior to PTZ administration. Neurological deficits and infarct volume were estimated 3 days after ET-1 administration and seizure score was assessed during the first 20 min after PTZ administration. The safety of 3,5-DBr-D-Tyr was evaluated in control animals using telemetry to measure cardiovascular parameters and immunostaining to assess the level of activated caspase-3. 3,5-DBr-D-Tyr significantly improved neurological function and reduced infarct volume in the brain even when the treatment was initiated 3 h after the onset of MCAo. 3,5-DBr-D-Tyr significantly depressed PTZ-induced seizures. 3,5-DBr-D-Tyr did not cause significant changes in arterial blood pressure, heart rate and spontaneous locomotor activity, nor did it increase the number of activated caspase-3 positive cells in the brain. We conclude that 3,5-DBr-D-Tyr, by alleviating the deleterious effects of MCAo and PTZ in rats with no obvious intrinsic effects on cardiovascular parameters and neurodegeneration, exhibits promising potential as a novel therapeutic direction for stroke and seizures. © 2010 Springer-Verlag.
CITATION STYLE
Cao, W., Glushakov, A., Shah, H. P., Mecca, A. P., Sumners, C., Shi, P., … Martynyuk, A. E. (2011). Halogenated aromatic amino acid 3,5-dibromo-D-tyrosine produces beneficial effects in experimental stroke and seizures. Amino Acids, 40(4), 1151–1158. https://doi.org/10.1007/s00726-010-0739-4
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