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.