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

Liu, Xinfeng; Fawcett, John R.; Thorne, Robert G.; DeFor, Terese A.; Frey, William H.

doi:10.1016/s0022-510x(01)00532-9

Cited by 218 publications

(147 citation statements)

References 21 publications

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“…In a work by , INA of IGF-1 was shown to significantly reduce infarct volume and improve neurological function following focal cerebral ischemia in rats, solving deficit in motor, sensory, reflex and vestibulomotor functions [21]. Similarly, intranasal delivery of IGF-1 has been found to recuperate neurological function in adult rats after middle cerebral artery occlusion [21,22]. Intranasal IGF-1 significantly reduced infarct volumes and hemispheric swelling and improved neurologic function, assessed by the postural reflex, flexor response and adhesive tape tests.…”

Section: Growth Factor Inhalation and Hypoxic-ischemic Brain Injurymentioning

confidence: 99%

“…However, intranasal delivery of IGF-1 has been found to improve neurological function in adult rats after hypoxic-ischemic brain damage [21,22]. In a work by , INA of IGF-1 was shown to significantly reduce infarct volume and improve neurological function following focal cerebral ischemia in rats, solving deficit in motor, sensory, reflex and vestibulomotor functions [21].…”

Section: Growth Factor Inhalation and Hypoxic-ischemic Brain Injurymentioning

confidence: 99%

See 1 more Smart Citation

Inhalation of growth factors and apo-transferrin to protect and repair the hypoxic-ischemic brain

Clausi

Paez

Pasquini

et al. 2016

Pharmacological Research

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Section: Growth Factor Inhalation and Hypoxic-ischemic Brain Injurymentioning

confidence: 99%

Section: Growth Factor Inhalation and Hypoxic-ischemic Brain Injurymentioning

confidence: 99%

Inhalation of growth factors and apo-transferrin to protect and repair the hypoxic-ischemic brain

Clausi

Paez

Pasquini

et al. 2016

Pharmacological Research

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“…A variety of nasal delivery methods are typically used in studies investigating nose-tobrain delivery in rodents, but very few studies specifically and consistently deposit drug on the olfactory epithelium. The most commonly used nasal administration modes are nose drops (18)(19)(20)(21), in which the animal is placed on its back in a supine position while liquid drops are snorted into the nasal cavity, or inserting a soft catheter connected to a microsyringe into the nasal cavity and applying a volume of drug a set distance into the nasal cavity from the naris (11,22). These methods may effectively deliver drug to the nasal cavity; however, they tend to involve a large dose volume resulting in saturation of both the respiratory and olfactory epithelium.…”

Section: Introductionmentioning

confidence: 99%

Effects of Localized Hydrophilic Mannitol and Hydrophobic Nelfinavir Administration Targeted to Olfactory Epithelium on Brain Distribution

Hoekman

2011

AAPS PharmSciTech

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Abstract. Many nasally applied compounds gain access to the brain and the central nervous system (CNS) with varying degree. Direct nose-to-brain access is believed to be achieved through nervous connections which travel from the CNS across the cribriform plate into the olfactory region of the nasal cavity. However, current delivery strategies are not targeted to preferentially deposit drugs to the olfactory at cribriform. Therefore, we have developed a pressurized olfactory delivery (POD) device which consistently and non-invasively deposited a majority of drug to the olfactory region of the nasal cavity in rats. Using both a hydrophobic drug, mannitol (log P=−3.1), and a hydrophobic drug, nelfinavir (log P=6.0), and POD device, we compared brain and blood levels after nasal deposition primarily on the olfactory region with POD or nose drops which deposited primarily on the respiratory region in rats. POD administration of mannitol in rats provided a 3.6-fold (p<0.05) increase in cortex-to-blood ratio, compared to respiratory epithelium deposition with nose drop. Administration of nelfinavir provided a 13.6-fold (p<0.05) advantage in cortex-to-blood ratio with POD administration, compared to nose drops. These results suggest that increasing the fraction of drug deposited on the olfactory region of the nasal cavity will result in increased direct nose-to-brain transport.

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“…In rats, intranasal administration of IGF-I exerted a neuroprotective effect, even when initiated 25 min after the onset of middle cerebral artery occlusion; IGF-I at 150 µg reduced the infarct volume by 63% and improved the neurologic deficit tests of motor, sensory, reflex, and vestibulomoter functions (82).…”

Section: Therapeutic Implication For Intranasal Administration Of Insmentioning

confidence: 95%

New Twist on Neuronal Insulin Receptor Signaling in Health, Disease, and Therapeutics

et al. 2005

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Abstract. Long after the pioneering studies documenting the existence of insulin (year 1967) and insulin receptor (year 1978) in brain, the last decade has witnessed extraordinary progress in the understanding of brain region-specific multiple roles of insulin receptor signalings in health and disease. In the hypothalamus, insulin regulates food intake, body weight, peripheral fat deposition, hepatic gluconeogenesis, reproductive endocrine axis, and compensatory secretion of counter-regulatory hormones to hypoglycemia. In the hippocampus, insulin promotes learning and memory, independent of the glucoregulatory effect of insulin. Defective insulin receptor signalings are associated with the dementia in normal aging and patients with age-related neurodegenerative diseases (e.g., Alzheimer's disease); the cognitive impairment can be reversed with systemic administration of insulin in the euglycemic condition. Intranasal administration of insulin enhances memory and mood and decreases body weight in healthy humans, without causing hypoglycemia. In the hypothalamus, insulin-induced activation of the phosphoinositide 3-kinase pathway followed by opening of ATP-sensitive K + channel has been shown to be related to multiple effects of insulin. However, the precise molecular mechanisms of insulin's pleiotropic effects still remain obscure. More importantly, much remains unknown about the quality control mechanisms ensuring correct conformational maturation of the insulin receptor, and the cellular mechanisms regulating density of cell surface functional insulin receptors.

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

Cited by 218 publications

References 21 publications

Inhalation of growth factors and apo-transferrin to protect and repair the hypoxic-ischemic brain

Inhalation of growth factors and apo-transferrin to protect and repair the hypoxic-ischemic brain

Effects of Localized Hydrophilic Mannitol and Hydrophobic Nelfinavir Administration Targeted to Olfactory Epithelium on Brain Distribution

New Twist on Neuronal Insulin Receptor Signaling in Health, Disease, and Therapeutics

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