Sani Sepehr, Jobe Kirk, Smith Adam, Kordower Jeffrey H, Bakay Roy A E
Department of Neurosurgery, Rush University Medical Center, Chicago, Illinois 60612, USA.
J Neurosurg. 2007 Oct;107(4):809-13. doi: 10.3171/JNS-07/10/0809.
Given the success of deep brain stimulation (DBS) in a variety of applications (for example, Parkinson disease and essential tremor), other indications for which there is currently little effective therapy are being evaluated for clinical use of DBS. Obesity may be one such indication. Studies of the control of feeding and appetite by neurosurgical lesioning have been completed previously. This study was conducted to test the authors' hypothesis that continuous bilateral stimulatory inhibition of the rat lateral hypothalamic nucleus (LH) would lead to significant and sustained decrease in food intake and subsequent weight loss.
Sixteen Sprague-Dawley rats were maintained on a high-fat diet. Daily food intake and weight gain were measured for 7 days, at which time the animals underwent stereotactic placement of 0.25-mm-diameter bipolar stimulating electrodes bilaterally in the LH. On postoperative Day 7, eight animals began to receive continuous stimulation of the LH. The remaining eight animals were left unstimulated as the control group. Individual animal weight, food intake, and water intake were monitored daily and continuously throughout the experiment until postoperative Day 24.
There was a decreased rate of weight gain after surgery in all animals, but the unstimulated group recovered and resumed a linear weight gain curve. The stimulated group, however, failed to show weight gain and remained below the mean baseline for body mass. There was a significant weight loss between the stimulated and unstimulated groups. On postoperative Day 24, compared with the day of surgery (Day 0), the unstimulated group had a mean weight gain of 13.8%, whereas the stimulated group had a 2.3% weight loss on average (p = 0.001), yielding a 16.1% weight difference between the two groups.
Bilateral electrical stimulatory inhibition of the LH is effective in causing significant and sustained weight loss in rats.
鉴于深部脑刺激(DBS)在多种应用(如帕金森病和特发性震颤)中取得的成功,目前正在评估DBS在临床应用中的其他适应证,而这些适应证目前几乎没有有效的治疗方法。肥胖可能就是这样一种适应证。先前已经完成了通过神经外科损伤来控制进食和食欲的研究。本研究旨在验证作者的假设,即持续双侧刺激抑制大鼠下丘脑外侧核(LH)会导致食物摄入量显著且持续减少,进而体重减轻。
16只Sprague-Dawley大鼠维持高脂饮食。连续7天测量每日食物摄入量和体重增加情况,此时对动物进行立体定向手术,将直径0.25毫米的双极刺激电极双侧植入LH。术后第7天,8只动物开始接受LH的持续刺激。其余8只动物不接受刺激作为对照组。在整个实验过程中直至术后第24天,每天持续监测每只动物的体重、食物摄入量和饮水量。
所有动物术后体重增加速率均降低,但未受刺激组恢复并重新呈现线性体重增加曲线。然而,受刺激组未能显示体重增加,且体重仍低于平均基线水平。受刺激组与未受刺激组之间存在显著体重差异。术后第24天,与手术当天(第0天)相比,未受刺激组平均体重增加了13.8%,而受刺激组平均体重下降了2.3%(p = 0.001),两组之间体重差异为16.1%。
双侧电刺激抑制LH可有效使大鼠体重显著且持续减轻。