Intranasal administration of insulin-like growth factor-I bypasses the blood-brain barrier and protects against focal cerebral ischemic damage

Background: Insulin-like growth factor-I (IGF-I) has: been shown to protect against stroke in rats when administered intracerebroventricularly. Howeve r, this invasive method of administration is not practical for the large nu mber of individuals who require treatment for stroke. Intranasal (IN) deliv ery offers a noninvasive method of bypassing the blood-brain barrier (BBB) to deliver IGF-I and other neurotrophic factors to the brain. Here, we demo nstrate for the first time the therapeutic benefit of IN IGF-I in rats foll owing middle cerebral artery occlusion (MCAO). Methods: A blinded, vehicle- controlled study of IN IGF-I was performed using the intraluminal suture oc clusion model. Rats were randomly divided into vehicle-control, 37.5 and 15 0 mug IGF-I-treated groups. Treatments occurred at 10 min after onset of 2 h of MCAO, and then 24 and 48 h later. Four neurologic behavioral tests wer e performed 4, 24, 48 and 72 h after the onset of MCAO. Corrected infarct v olumes were evaluated 72 h after the onset of MCAO. Results: Treatment with the 150 mug IGF-I significantly reduced the infarct volume by 63% vs, cont rol (p = 0.004), and improved all the neurologic deficit tests of motor, se nsory, reflex and vestibulomotor functions(p < 0.01). However, the 37.5-mug dose of IGF-I was ineffective. Conclusion: While IGF-I does not cross the BBB efficiently, it can be delivered to the brain directly from the nasal c avity following IN administration, bypassing the BBB. IN IGF-I markedly red uced infarct volume and improved neurologic function following focal cerebr al ischemia. This noninvasive, simple and cost-effective method is a potent ial treatment for stroke. (C) 2001 Elsevier Science B.V. All rights reserve d.