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Effects of a new thyrotropin-releasing hormone derivative on behavioral changes after focal cerebral ischemia in rats.

Abstract
We observed the effects of a new thyrotropin-releasing hormone derivative, YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate), on behavioral changes in rats for 3 weeks after focal cerebral ischemia. Under halothane anesthesia, the left middle cerebral artery was occluded via a transretro-orbital approach. YM-14673 was administered just after the operation and once a day for 3 weeks. Neurologic deficits, including hemiplegia and abnormal posture, and disturbance of passive avoidance learning were present in solvent-treated control rats for the entire 3 weeks. YM-14673 at 0.1 or 0.3 mg/kg i.p. or 1 mg/kg p.o. significantly accelerated the recovery of neurologic deficits and ameliorated cognitive disturbance compared with the solvent-treated controls although the drug at 0.1 and 0.3 mg/kg i.p. did not influence the size of the ischemic infarct. YM-14673 mitigated the behavioral disturbances in this model of chronic focal cerebral ischemia. We also discuss the suitability of this model for the evaluation of drugs.
AuthorsM Yamamoto, A Tamura, T Kirino, M Shimizu, K Sano
JournalStroke (Stroke) Vol. 20 Issue 3 Pg. 362-6 (Mar 1989) ISSN: 0039-2499 [Print] United States
PMID2493690 (Publication Type: Journal Article)
Chemical References
  • Azetidines
  • Azetines
  • Dipeptides
  • Thyrotropin-Releasing Hormone
  • azetirelin
Topics
  • Animals
  • Avoidance Learning (drug effects)
  • Azetidines (pharmacology)
  • Azetines (pharmacology)
  • Behavior, Animal (drug effects)
  • Brain Ischemia (complications, pathology, psychology)
  • Cerebral Infarction (pathology)
  • Dipeptides (pharmacology)
  • Male
  • Nervous System Diseases (etiology, physiopathology)
  • Rats
  • Rats, Inbred Strains
  • Reaction Time
  • Thyrotropin-Releasing Hormone (analogs & derivatives)

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