Open AccessHalogenated aromatic amino acid 3,5-dibromo-d-tyrosine produces beneficial effects in experimental stroke and seizures
Author(s) -
Wengang Cao,
Alexander V. Glushakov,
Hina P. Shah,
Adam P. Mecca,
Colin Sumners,
Peng Shi,
Christoph N. Seubert,
Anatoly E. Martynyuk
Publication year - 2010
Publication title -
amino acids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.894
H-Index - 118
eISSN - 1438-2199
pISSN - 0939-4451
DOI - 10.1007/s00726-010-0739-4
Subject(s) - medicine , bolus (digestion) , stroke (engine) , tyrosine , epilepsy , pharmacology , anesthesia , endocrinology , chemistry , biochemistry , mechanical engineering , engineering , psychiatry
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.