Saatman K E, Contreras P C, Smith D H, Raghupathi R, McDermott K L, Fernandez S C, Sanderson K L, Voddi M, McIntosh T K
Center for Injury Research, Department of Neurosurgery, University of Pennsylvania, Philadelphia 19104, USA.
Exp Neurol. 1997 Oct;147(2):418-27. doi: 10.1006/exnr.1997.6629.
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.
我们评估了胰岛素样生长因子-1（IGF-1）在减轻侧方液压冲击（FP）脑损伤后神经行为缺陷方面的疗效。将雄性Sprague-Dawley大鼠（体重345 - 425克，n = 88）麻醉后，使其遭受中度严重程度（2.4 - 2.9个大气压）的FP脑损伤。在研究1中，于损伤后15分钟通过皮下注射给予IGF-1（1.0毫克/千克，n = 9）或赋形剂（n = 14），并在接下来的14天里每隔12小时以同样方式给药。在连续14天每日评估的动物中，IGF-1治疗在2周期间减轻了运动功能障碍（P < 0.02）。在研究2中，于损伤后15分钟植入皮下泵，通过该泵给予IGF-1（4毫克/千克/天，n = 8只未受伤动物，n = 13只受伤动物）或赋形剂（n = 8只未受伤动物，n = 13只受伤动物），持续2周。给予IGF-1与体重增加以及轻度、短暂的低血糖有关，这种情况在脑损伤动物中更为明显。在损伤后2周（P < 0.05），而非48小时或1周时，接受IGF-1的脑损伤动物与接受赋形剂的动物相比，神经运动功能有所改善。给予IGF-1还增强了脑损伤动物在损伤后2周时的学习能力（P < 0.03）和记忆保持能力（P < 0.01）。综上所述，这些数据表明，创伤后长期给予营养因子IGF-1可能对改善与创伤性脑损伤相关的神经行为功能障碍有效。
