Prepro-thyrotropin-releasing hormone 178-199 exerts partial protection against cerebral ischemia in adult rats.
We examined in the present study the effects of the centrally administered prepro-thyrotropin-releasing-hormone 178-199 (prepro-TRH 178-199) on cerebral ischemia induced by ligation of the middle cerebral artery (MCA) in adult Sprague-Dawley rats. Animals were intracerebrally injected with prepro-TRH 178-199 (6 microg/kg or 200 microg/kg) or saline 1-2 h before ligation of MCA. Ischemic animals that received prepro-TRH 178-199, regardless of dosage, displayed some amelioration (20%) of motor asymmetry associated with MCA ligation, while ischemic animals that received saline continued to exhibit significant asymmetrical behaviors. Interestingly, triphenyltetrazolium chloride staining (a marker for tissue metabolic activity) revealed that four of five ischemic animals that received 200 microg/kg prepro-TRH 178-199 showed a marked reduction (90-100%) in the infarction of the frontal cortex, although the posterior sections of the cortex remained infarcted. In contrast, ischemic animals that received 6 microg/kg prepro-TRH 178-199 demonstrated infarction that did not differ in size and extent from those that received saline. Post hoc examination revealed that ischemic animals treated with 200 microg/kg prepro-TRH 178-199 had significantly lower corticosterone (CORT) levels (115+/-23 ng/ml) than ischemic animals treated with 6 microg/kg prepro-TRH 178-199 or saline (288+/-51 ng/ml). The present observation provides the first evidence that prepro-TRH 178-199 can promote neuroprotection against cerebral ischemia.
Borlongan
C V
CV
National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, Cellular Neurophysiology, Baltimore, MD 21224, USA.
Stahl
C E
CE
Redei
E
E
Wang
Y
Y
D000375:Aging; D000818:Animals; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D002544:Cerebral Infarction / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D005625:Frontal Lobe / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011498:Protein Precursors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*
D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011498:Protein Precursors; C057640:prepro-thyrotropin-releasing hormone (178-199); D013973:Thyrotropin-Releasing Hormone; D006854:Hydrocortisone