视神经半损伤后复合神经营养因子辅助再生的动态PVEP研究

Studies on PVEP measurements of auxiliary compound neurotropic factors on repair and regeneration after hemi-optic nerve injury

目的 :探讨视神经 (opticnerve ,ON)损伤后的自然修复再生和用脑源性神经营养因子 (BDNF)及睫状神经营养因子 (CNTF)互补辅助再生的图形翻转视觉诱发电位 (PVEP)变化特征 ,寻找ON有效再生的新途径。方法 :将 4 0只猫作为实验对象 ,术前随机平均分为 4组 :正常对照组、球后ON半径切断组 (ON1/2I)、ON半径切断并定时向玻璃体内注射生理盐水对照组 (ON1/2I +PS)和ON半径切断并定时向玻璃体内注射BDNF和CNTF复合因子辅助再生组 (ON1/2I +BF)。经眶外侧入路行手术开眶 ,在球后 5mm处测量ON直径数值 ,并用宝石卡尺刀行ON半径切断术。ON1/2I+BF组在术后即日注射BDNF和CNTF复合液 (10ng) ,并在以后注射等量BDNF和CNTF复合液 ,2次 /w。在ON损伤后 1个月、4个月和 8个月 ,3次行PVEP动态检测。结果 :在ON1/2损伤后 1个月时 ,与N组相比 ,ON1/2损伤各组PVEP的N1 P1振幅显著降低和P1潜时延迟 ;ON1/2I组和ON1/2I+PS组与ON1/2I+BF组比较 ,也出现了PVEP的N1 P1振幅降低和P1潜时的延迟。在ON1/2损伤后第 4个月时 ,ON1/2I组和ON1/2I+PS组与N组比较 ,其PVEP的P1潜时显著延迟 (P<0 .0 0 1,P <0 .0 0 1)和N1 P1幅度显著降低 (P <0 .0 0 1,P <0 .0 0 1)。而ON1/2I +BF组与N组比较 ,两者PVEP的P1潜时和N1

Objective:To investigate and discuss PVEP measurements of neurotrophins(BDNF and CNTF) in their role in the repair and regeneration of the optic nerve(ON) after hemi injury. To find new approaches for functional and effective optic nerve regeneration.Methods:Cats were used as experimental models. Before surgery,the animals were randomly divided into 4 groups of 10 cats each:normal control group(N);ON1/2 hemidiameter incision group(ON1/2I);ON1/2 incision group that received injections of saline solution(2 times/wk) into the intraocular vitreous(ON1/2I+PS);ON1/2 incision group that received injections of ciliary neurotrophic factor(CNTF) and brain derived neurotrophic factor(BDNF) into the intraocular vitreous on the same schedule(2 times/wk)(ON1/2I+BF). After surgery was performed on the cats in the experimental groups in order to establish models of ON hemidiameter incision(ON1/2I),the animals were maintained for four weeks,sixteen weeks and thirty two weeks,respectively,under the same visual environment conditions. Pattern visual evoked potential(PVEP) measurements were performed on N,ON1/2I,ON1/2I+PSW and ON1/2I+BF three times(in the 1 st ,4 th and 8 th month). Results of PVEP measurements taken from the eyes of both the normal and experimental animal models were then analyzed with a two pair t test.Results:During the first month after 1/2 hemidiameter optic nerve injury when compared with N,PVEP measurements showed a decreased N 1 P 1 amplitude and a increased P 1 latency for all ON1/2 injury groups. When ON1/2I+BF was compared,PVEP measurements showed a decreased N 1 P 1 amplitude and an increased P 1 latency for ON1/2I and ON1/2I+PS. The fourth month after 1/2 diameter optic nerve injury,ON1/2I and ON1/2I+PS were compared to N in N 1 P 1 amplitude and P 1 latency measurements from PVEP. There was no significant recovery. The N 1 P 1 amplitude and P 1 latency measurements from their PVEP showed a lower amplitude and in creased latency compared to ON1/2I+BF. When ON1/2I+BF was compared with N,there was also a significant difference in the N 1 P 1 amplitude and P 1 latency of PVEP measurements. But the slopes of the curves of the N 1 P 1 amplitude and P 1 latency from PVEP measurements of ON1/2I+BF showed some recovery when compared to the first month. The eighth month after 1/2 of diameter optic nerve injury when compared to N,PVEP of N 1 P 1 amplitudes were still lower and P 1 had a delayed latency in ON1/2 and ON1/2I+PS. The curve of the N 1 P 1 amplitude and P 1 latency of PVEP on ON1/2 and ON1/2I+PS was not found to have recovered significantly when analyzing the results of PVEP measurements taken at the first month. In addition,there was no significant difference between ON1/2I+BF and N when ON1/2I+BF was compared with N for PVEP measurements of P 1 latency. But N 1 P 1 amplitude was still lower compared to that of N,and the difference was significant(P<0.05). There was also a significant difference(P<0.01) when ON1/2I+BF was compared to ON1/2 and ON1/2I+PS. There was a significant difference(P<0.01) between ON1/2I+BF in the eighth month and in the fourth month for PVEP measurements of N 1 P 1 amplitude and P 1 latency. The slopes of the curves of the N 1 P 1 amplitude and P 1 latency of PVEP in the eighth month showed a recovery.Conclusion:There were dynamic changes in the visual electrophysiology before and after optic nerve injury and during the periods of regeneration. PVEP measurements revealed that the P 1 latency was severely delayed and the N 1 P 1 had a big decrease in amplitude during the early stages after optic nerve injury at 1/2 of diameter. However,the first,fourth and eighth month after treatment with neurotrophic factors to resist the side effects from optic nerve injury, PVEP measurements showed that the P 1 latency decreased and N 1 P 1 amplitude gradually increased. The results of these changes proved that injured ON recovered transmitter function(input/output) for visual information and regeneration was successful. The in