Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury

Kathryn E. Saatman; Patricia C. Contreras; Douglas H. Smith; Ramesh Raghupathi; Kelli L. McDermott; Seamus C. Fernandez; Kristin L. Sanderson; Madhu Voddi; Tracy K. McIntosh

doi:10.1006/exnr.1997.6629

Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury

Kathryn E. Saatman, Patricia C. Contreras, Douglas H. Smith, Ramesh Raghupathi, Kelli L. McDermott, Seamus C. Fernandez, Kristin L. Sanderson, Madhu Voddi, Tracy K. McIntosh

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166 Scopus citations

Abstract

We evaluated the efficacy of insulin-like growth factor-1 (IGF-1) in attenuating neurobehavioral deficits following lateral fluid percussion (FP) brain injury. Male Sprague-Dawley rats (345-425 g, n = 88) were anesthetized and subjected to FP brain injury of moderate severity (2.4-2.9 atm). In Study 1, IGF-1 (1.0 mg/kg, n = 9) or vehicle (n = 14) was administered by subcutaneous injection at 15 min postinjury and similarly at 12-h intervals for 14 days. In animals evaluated daily for 14 days, IGF-1 treatment attenuated motor dysfunction over the 2-week period (P < 0.02). In Study 2, IGF-1 (4 mg/kg/day, n = 8 uninjured, n = 13 injured) or vehicle (n = 8 uninjured, n = 13 injured) was administered for 2 weeks via a subcutaneous pump implanted 15 min postinjury. IGF-1 administration was associated with increased body weight and mild, transient hypoglycemia which was more pronounced in brain-injured animals. At 2 weeks postinjury (P < 0.05), but not at 48 h or 1 week, brain-injured animals receiving IGF-1 showed improved neuromotor function compared with those receiving vehicle. IGF-1 administration also enhanced learning ability (P < 0.03) and memory retention (P < 0.01) in brain-injured animals at 2 weeks postinjury. Taken together, these data suggest that chronic, posttraumatic administration of the trophic factor IGF-1 may be efficacious in ameliorating neurobehavioral dysfunction associated with traumatic brain injury.

Original language	English
Pages (from-to)	418-427
Number of pages	10
Journal	Experimental Neurology
Volume	147
Issue number	2
DOIs	https://doi.org/10.1006/exnr.1997.6629
State	Published - Oct 1997

Bibliographical note

Funding Information:
This study was supported, in part, by grants from the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (RO1-NS26818, PO1-NS08803), a grant from the National Institute of General Medical Sciences (RO1-GM34690), a Merit Review Grant from the Veterans Administration, and Cephalon. We gratefully acknowledge the technical support of Dr. Lei Fan, Brian Perri, and Kevin Pool and the administrative assistance of Laura Meehan. The procedures used throughout this study were approved by the Institutional Animal Care and Use Committee of the University of Pennsylvania and were performed in accordance with standards published in the Guide for the Care and Use of Laboratory Animals, U.S. Department of Health and Human Services (Publication 85-23, 1985).

ASJC Scopus subject areas

Neurology
Developmental Neuroscience

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@article{37ebad010d044ece90e6706137ac0868,

title = "Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury",

abstract = "We evaluated the efficacy of insulin-like growth factor-1 (IGF-1) in attenuating neurobehavioral deficits following lateral fluid percussion (FP) brain injury. Male Sprague-Dawley rats (345-425 g, n = 88) were anesthetized and subjected to FP brain injury of moderate severity (2.4-2.9 atm). In Study 1, IGF-1 (1.0 mg/kg, n = 9) or vehicle (n = 14) was administered by subcutaneous injection at 15 min postinjury and similarly at 12-h intervals for 14 days. In animals evaluated daily for 14 days, IGF-1 treatment attenuated motor dysfunction over the 2-week period (P < 0.02). In Study 2, IGF-1 (4 mg/kg/day, n = 8 uninjured, n = 13 injured) or vehicle (n = 8 uninjured, n = 13 injured) was administered for 2 weeks via a subcutaneous pump implanted 15 min postinjury. IGF-1 administration was associated with increased body weight and mild, transient hypoglycemia which was more pronounced in brain-injured animals. At 2 weeks postinjury (P < 0.05), but not at 48 h or 1 week, brain-injured animals receiving IGF-1 showed improved neuromotor function compared with those receiving vehicle. IGF-1 administration also enhanced learning ability (P < 0.03) and memory retention (P < 0.01) in brain-injured animals at 2 weeks postinjury. Taken together, these data suggest that chronic, posttraumatic administration of the trophic factor IGF-1 may be efficacious in ameliorating neurobehavioral dysfunction associated with traumatic brain injury.",

author = "Saatman, {Kathryn E.} and Contreras, {Patricia C.} and Smith, {Douglas H.} and Ramesh Raghupathi and McDermott, {Kelli L.} and Fernandez, {Seamus C.} and Sanderson, {Kristin L.} and Madhu Voddi and McIntosh, {Tracy K.}",

note = "Funding Information: This study was supported, in part, by grants from the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (RO1-NS26818, PO1-NS08803), a grant from the National Institute of General Medical Sciences (RO1-GM34690), a Merit Review Grant from the Veterans Administration, and Cephalon. We gratefully acknowledge the technical support of Dr. Lei Fan, Brian Perri, and Kevin Pool and the administrative assistance of Laura Meehan. The procedures used throughout this study were approved by the Institutional Animal Care and Use Committee of the University of Pennsylvania and were performed in accordance with standards published in the Guide for the Care and Use of Laboratory Animals, U.S. Department of Health and Human Services (Publication 85-23, 1985).",

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doi = "10.1006/exnr.1997.6629",

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AU - Saatman, Kathryn E.

AU - Contreras, Patricia C.

AU - Smith, Douglas H.

AU - Raghupathi, Ramesh

AU - McDermott, Kelli L.

AU - Fernandez, Seamus C.

AU - Sanderson, Kristin L.

AU - Voddi, Madhu

AU - McIntosh, Tracy K.

N1 - Funding Information: This study was supported, in part, by grants from the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (RO1-NS26818, PO1-NS08803), a grant from the National Institute of General Medical Sciences (RO1-GM34690), a Merit Review Grant from the Veterans Administration, and Cephalon. We gratefully acknowledge the technical support of Dr. Lei Fan, Brian Perri, and Kevin Pool and the administrative assistance of Laura Meehan. The procedures used throughout this study were approved by the Institutional Animal Care and Use Committee of the University of Pennsylvania and were performed in accordance with standards published in the Guide for the Care and Use of Laboratory Animals, U.S. Department of Health and Human Services (Publication 85-23, 1985).

PY - 1997/10

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N2 - We evaluated the efficacy of insulin-like growth factor-1 (IGF-1) in attenuating neurobehavioral deficits following lateral fluid percussion (FP) brain injury. Male Sprague-Dawley rats (345-425 g, n = 88) were anesthetized and subjected to FP brain injury of moderate severity (2.4-2.9 atm). In Study 1, IGF-1 (1.0 mg/kg, n = 9) or vehicle (n = 14) was administered by subcutaneous injection at 15 min postinjury and similarly at 12-h intervals for 14 days. In animals evaluated daily for 14 days, IGF-1 treatment attenuated motor dysfunction over the 2-week period (P < 0.02). In Study 2, IGF-1 (4 mg/kg/day, n = 8 uninjured, n = 13 injured) or vehicle (n = 8 uninjured, n = 13 injured) was administered for 2 weeks via a subcutaneous pump implanted 15 min postinjury. IGF-1 administration was associated with increased body weight and mild, transient hypoglycemia which was more pronounced in brain-injured animals. At 2 weeks postinjury (P < 0.05), but not at 48 h or 1 week, brain-injured animals receiving IGF-1 showed improved neuromotor function compared with those receiving vehicle. IGF-1 administration also enhanced learning ability (P < 0.03) and memory retention (P < 0.01) in brain-injured animals at 2 weeks postinjury. Taken together, these data suggest that chronic, posttraumatic administration of the trophic factor IGF-1 may be efficacious in ameliorating neurobehavioral dysfunction associated with traumatic brain injury.

AB - We evaluated the efficacy of insulin-like growth factor-1 (IGF-1) in attenuating neurobehavioral deficits following lateral fluid percussion (FP) brain injury. Male Sprague-Dawley rats (345-425 g, n = 88) were anesthetized and subjected to FP brain injury of moderate severity (2.4-2.9 atm). In Study 1, IGF-1 (1.0 mg/kg, n = 9) or vehicle (n = 14) was administered by subcutaneous injection at 15 min postinjury and similarly at 12-h intervals for 14 days. In animals evaluated daily for 14 days, IGF-1 treatment attenuated motor dysfunction over the 2-week period (P < 0.02). In Study 2, IGF-1 (4 mg/kg/day, n = 8 uninjured, n = 13 injured) or vehicle (n = 8 uninjured, n = 13 injured) was administered for 2 weeks via a subcutaneous pump implanted 15 min postinjury. IGF-1 administration was associated with increased body weight and mild, transient hypoglycemia which was more pronounced in brain-injured animals. At 2 weeks postinjury (P < 0.05), but not at 48 h or 1 week, brain-injured animals receiving IGF-1 showed improved neuromotor function compared with those receiving vehicle. IGF-1 administration also enhanced learning ability (P < 0.03) and memory retention (P < 0.01) in brain-injured animals at 2 weeks postinjury. Taken together, these data suggest that chronic, posttraumatic administration of the trophic factor IGF-1 may be efficacious in ameliorating neurobehavioral dysfunction associated with traumatic brain injury.

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Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury

Abstract

Bibliographical note

ASJC Scopus subject areas

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