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

被引:166
作者
Saatman, KE
Contreras, PC
Smith, DH
Raghupathi, R
McDermott, KL
Fernandez, SC
Sanderson, KL
Voddi, M
McIntosh, TK
机构
[1] UNIV PENN, CTR INJURY RES, DEPT BIOENGN, PHILADELPHIA, PA 19104 USA
[2] CEPHALON INC, W CHESTER, PA USA
关键词
D O I
10.1006/exnr.1997.6629
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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, ICF-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. (C) 1997 Academic Press.
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页码:418 / 427
页数:10
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