Neuroprotective effect of the neurotensin analogue JMV-449 in a mouse model of permanent middle cerebral ischaemia.
The neuroprotective effect of the neurotensin analogue H-Lys-psi(CH2NH)Lys-Pro-Tyr-Ile-Leu-OH (JMV-449) was assessed in a mouse model of permanent distal middle cerebral artery occlusion. Mice were injected with 0.6 nmol JMV-449 or vehicle i.c.v. immediately after ischaemia. The core temperature declined by 6-7 degrees C after 30 min and the hypothermia persisted for 4-5 h. JMV-449 treatment was able to reduce the infarct volume significantly both at 24 h and 14 days after onset of ischaemia. No neuroprotective effect could be seen if the mice were kept normothermic after the JMV-449 treatment suggesting that the neuroprotective effect is mediated via the hypothermia.
Torup
Lars
L
Department of Neurodegenerative Disorders, H Lundbeck A/S, Ottiliavej 9, 2500, Valby, Denmark. lto@lundbeck.com
Borsdal
Jeanett
J
Sager
Thomas
T
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009496:Neurotensin / Q000031:analogs & derivatives / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D009842:Oligopeptides; C077827:JMV 449; D009496:Neurotensin