Corticotrophin-releasing factor antagonist inhibits neuronal damage induced by focal cerebral ischaemia or activation of NMDA receptors in the rat brain.
This study investigated the involvement of corticotrophin-releasing factor (CRF) in acute neuronal damage induced by focal cerebral ischaemia or pharmacological activation of NMDA receptors in the rat brain. Intracerebroventricular injection of a CRF receptor antagonist (alpha-helical CRF9-41), markedly inhibited ischaemic (61%) and excitotoxic (41%) brain damage. Peripheral injection of a glucocorticoid antagonist (RU38486) did not affect ischaemic damage. Ischaemic and excitotoxic damage caused increased hypothalamic concentrations of CRF. These data indicate that CRF mediates ischaemic and excitotoxic neuronal damage in the rat, but that this effect is not dependent on glucocorticoids.
Strijbos
P J
PJ
Department of Physiological Sciences, University of Manchester, UK.
Relton
J K
JK
Rothwell
N J
NJ
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007276:Injections, Intraventricular; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*
D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D015735:Mifepristone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)