Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury.
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.
Saatman
K E
KE
Center for Injury Research, Department of Neurosurgery, University of Pennsylvania, Philadelphia 19104, USA.
Contreras
P C
PC
Smith
D H
DH
Raghupathi
R
R
McDermott
K L
KL
Fernandez
S C
SC
Sanderson
K L
KL
Voddi
M
M
McIntosh
T K
TK
D000818:Animals; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D015918:Infusion Pumps, Implantable; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007859:Learning Disabilities / Q000209:etiology / Q000517:prevention & control; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009069:Movement Disorders / Q000209:etiology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors; D014949:Wounds, Nonpenetrating / Q000188:drug therapy
D018696:Neuroprotective Agents; D007334:Insulin-Like Growth Factor I