Non-invasive intranasal insulin-like growth factor-I reduces infarct volume and improves neurologic function in rats following middle cerebral artery occlusion.
Insulin-like growth factor-I (IGF-I) has been proposed as a treatment for stroke. However, it does not efficiently cross the blood-brain barrier (BBB). Intracerebroventricular injection of IGF-I has been shown to offer protection against cerebral ischemic damage in rats although this invasive method of administration may not be practical in humans. Non-invasive intranasal (IN) delivery of IGF-I to the brain is a promising alternative. We have assessed the therapeutic effect of IN IGF-I in rats following middle cerebral artery occlusion (MCAO). Treatment was initiated 10 min after the onset of MCAO and then again 24 and 48 h later. Intranasal dosing of 75 microg IGF-1 (225 microg total IGF-I over 48 h) significantly reduced corrected infarct volumes by 60% vs. control (P<0.01) and hemispheric swelling by 45.6% vs. control (P<0.05). Neurologic function, assessed by the postural reflex, flexor response and adhesive tape tests, was also improved by IN IGF-I as compared to control. Our study indicates IN delivery of IGF-1 holds significant promise as a non-invasive and efficacious method of bypassing the BBB for the treatment of stroke.
Liu
X F
XF
Stroke Laboratory, Alzheimer's Research Center, Department of Neurology, Regions Hospital, St. Paul, MN 55101, USA. Liuxx159@tc.umn.edu
Fawcett
J R
JR
Thorne
R G
RG
Frey
W H
WH
D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009831:Olfactory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology
D018696:Neuroprotective Agents; D007334:Insulin-Like Growth Factor I