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1.
高频刺激底丘脑核阻止帕金森病黑质多巴胺能神经元变性的 … 总被引:1,自引:0,他引:1
目的 评价电刺激底丘脑核(STN)对帕金森病黑质多巴胺能神经元变性的影响。方法 实验用大鼠随机分为四组:第1组 纹状体仅注射6-羟基多巴(6-0HDA);第2组 底丘脑核区插入电极进行刺激组;第3组 底丘脑核刺激后6-OHDA再注射纹状体组;第4组 假刺激 丘脑核后再注射6-OHDA入纹状体组。手术后6周,分别观察各组大鼠阿朴吗啡诱发旋转行为及黑质多巴胺能神经地改变情况。 相似文献
2.
损毁丘脑底核阻止6—OHDA对大鼠多巴胺能神经元的损?… 总被引:1,自引:0,他引:1
目的观察不同时期毁损丘脑底核对大鼠中脑黑质多巴胺神经元6-羟基多巴胺(6-OHDA)损伤的保护作用。方法将60只Wistar大鼠随机分为6组,每组10只。对照组采用6-0HDA立体定向注入大鼠右侧前脑内侧束(MFB)和中脑被盖腹侧区(VTA),制成偏侧帕金森病(PD)模型。实验组分为第Ⅰ、Ⅱ、Ⅲ、Ⅳ和Ⅴ组,分别于6-OHDA注射前7d、注射后1h、2h、3d、7d5个不同时间点,局部注射海藻氨酸( 相似文献
3.
神经节苷脂对帕金森病鼠旋转行为、纹状体多巴胺浓度及黑质病理的影响 总被引:4,自引:0,他引:4
目的观察神经节苷脂对帕金森病(Parkinsondisease,PD)鼠模型的旋转行为、纹状体多巴胺浓度及黑质病理的影响。方法将6-羟基多巴胺用立体定向法注入大鼠一侧中脑被盖腹侧区制作PD大鼠模型,并于同侧侧脑室注射混合型神经节苷脂(amixedgangliosidepreparation,GM),观察GM对由阿朴吗啡所诱发的旋转行为、受损侧纹状体多巴胺浓度及黑质病理的影响。结果GM能减轻PD大鼠模型的旋转行为、使受损侧纹状体多巴胺浓度下降和黑质神经细胞减少。结论GM可减轻6-羟基多巴胺对黑质多巴胺能神经元的损伤。 相似文献
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采用SD大鼠20只,15只为实验组,5只作为对照。用微量注射器将6-羟基多巴(6-OHDA)8ug/4ul分别注入大鼠右侧黑质致密部(SNc)和中脑腹侧背盖区(VTA),观察大鼠行为变化及黑质和纹状体形态学改变。结果:注药4周后,毁损组动物经阿朴吗啡诱发14只出现旋转,超过7转/分为12只(占80%),经反复测试结果稳定;旋转鼠行Nisl染色发现,右侧SNc和VTA区神经元数目明显减少;酪氨酸羟化酶(TH)免疫组织化学染色见:右侧SNc及纹状体区TH免疫反应(TH-IR)数目较对侧明显下降。对照组则无旋转行为和形态学改变。提示这种改进的方法建立大鼠帕金森氏病模型成功率明显提高。 相似文献
6.
一氧化氮与帕金森病大鼠模型神经损伤的研究 总被引:4,自引:1,他引:3
目的 研究一氧化氮(NO)在帕金森病(PD)大鼠模型神经损伤中的作用。方法 用高效液相色谱电化学法(HPLC-ET)及还原型辅酶Ⅱ(NADPH)黄递酶组化法观察NO在PD大鼠模型神经损伤中的作用。结果 神经型一氧化氮合成酶(nNOS)抑制剂7-硝基吲唑(7-NI)明显减少6-羟基多巴胺(6-OHDA)引起的纹状体多巴胺及其代谢产物的降低(P〈0.01);纹状体NADPH黄递酶阳性神经元可抵抗6-O 相似文献
7.
MPTP处理的小鼠和6—OHDA损毁的大鼠帕金林病模型病理变化 … 总被引:3,自引:0,他引:3
目的 比较MPTP处理的小鼠与6-OHDA损毁大鼠PD模型的病理变化。方法 应用免疫组化方法观察两种PD模型的中脑腹侧多巴胺能神经元,星形胶质细胞的变化。结果 免疫组化方法结果表明:C57BL小鼠在MPTP处理后,脑内酪氨酸羟化酶阳性神经元的数目从第4d开始有所减少,黑质区域的GFAP免疫阳性星形胶质细胞数目从第1d起即有增加,大鼠PD模型较早出现损毁侧TH免疫阳性神经元明显减少的现象,损毁2月后 相似文献
8.
目的 评价不同损毁程度 C57 B L 小鼠帕金森病( P D)模型纹状体多巴胺转运蛋白( D A T)的变化。方法 根据腹腔注射 M P T P 的天数将小鼠分为 1、3、5 和 7d 模型组以及对照组,静脉注射99m Tc T R O D A T16m Ci,1h 后处死行脑纹状体放射自显影,同时行免疫组化酪氨酸羟化酶( T H)染色。结果 对照组的放射自显影可见99m Tc T R O D A T1 于纹状体部位有高度放射性聚集,且两侧纹状体基本相同。注射 M P T P 1d 者,其纹状体的放射性浓集比对照组有所下降。注射 M P T P 3、5 及 7d 者,两侧纹状体的放射性浓集逐日降低,第 7d 者几乎消失。 T H 染色发现黑质 T H 阳性神经元亦随注射 M P T P 天数的增加而数量减少。结论 不同程度损毁的 C57 B L 小鼠 P D 模型可模拟 P D 的发展过程,99m Tc T R O D A T1 作为 D A T 的显影剂可用于早期诊断的神经显像学研究。 相似文献
9.
大鼠黑质和中脑腹侧被盖区注入6_羟基多巴胺(6-OHDA)建立帕金森病模型后,高频电刺激丘脑底核,观察模型鼠旋转行为改善程度,记录皮层和丘脑核区脑电图改变。结果表明,高频电刺激可使模型鼠旋转行为明显下降;脑电图示皮层兴奋性增强,而丘脑底核兴奋性下降。本研究提示:丘脑底核对帕金森病运动症状的控制发挥了重要作用,高频电刺激此核团可望成为帕金森病治疗的新途 相似文献
10.
MPTP处理的小鼠和6-OHDA损毁的大鼠帕金森病模型病理变化的比较 总被引:4,自引:0,他引:4
目的比较MPTP处理的小鼠与6-OHDA损毁大鼠PD模型的病理变化。方法应用免疫组化方法观察两种PD模型的中脑腹侧多巴胺能神经元,星形胶质细胞的变化。结果免疫组化方法结果表明:C57BL小鼠在MPTP处理后,脑内酪氨酸羟化酶阳性神经元的数目从第4d开始有所减少;黑质区域的GFAP免疫阳性星形胶质细胞数目从第1d起即有增加。大鼠PD模型较早出现损毁侧TH免疫阳性神经元明显减少的现象,损毁2月后几乎完全消失;而在黑质区的GFAP免疫阳性星形胶质细胞数目增多现象出现较晚。结论两种动物模型从不同侧面反映了帕金森病的病理特征,6-OHDA损毁中脑DA能神经元制成的大鼠PD模型比MPTP处理的C57BL小鼠PD模型更接近反映PD的病理变化。 相似文献
11.
Brigitte Piallat Abdelhamid Benazzouz Alim Louis Benabid 《The European journal of neuroscience》1996,8(7):1408-1414
Several studies have shown that antagonists of N -methyl-D-aspartate receptors provide protection of the dopaminergic nigrostriatal pathway in animal models of Parkinson's disease. Since the substantia nigra compacta receives a moderate glutamatergic innervation from the subthalamic nucleus, we tried to determine whether subthalamic nucleus lesion could prevent the toxicity of the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). Experiments were carried out on four groups of rats. Group 1 ( n = 10) received a unilateral injection of 6-hydroxydopamine in the striatum and group 2 ( n = 10) received kainic acid in the subthalamic nucleus. Group 3 ( n = 10) received an injection of kainic acid in the subthalamic nucleus and 1 week later an injection of 6-OHDA in the striatum. Group 4 ( n = 5) received the same treatment but kainic acid was replaced by saline. Apomorphine induced an ipsilateral rotation in rats of groups 2 and 3 and a contralateral rotation in rats of groups 1 and 4. The number of tyrosine hydroxylase-immunoreactive cells in the pars compacta of the substantia nigra was not significantly different between injected and non-injected sides in rats of groups 2 and 3, but was significantly decreased on the side ipsilateral to 6-OHDA striatal injection in rats of groups 1 and 4. These results show that subthalamic nucleus lesion provides neuroprotection of the dopaminergic nigrostriatal pathway against 6-OHDA toxicity and opens a new way for slowing or stopping the progression of Parkinson's disease. 相似文献
12.
J.M. Henderson L.E. Annett E.M. Torres S.B. Dunnett 《The European journal of neuroscience》1998,10(2):689-698
Recent studies in non-human primates support a role for the subthalamic nucleus in the expression of parkinsonian symptomatology, and it has been proposed that subthalamic lesions may provide a surgical treatment for the symptoms of Parkinson’s disease in humans. We have applied a broad range of behavioural tests to characterize the effects of lesions of the subthalamic nucleus on parkinsonian symptoms in the unilateral 6-hydroxydopamine (6-OHDA) lesioned marmoset (Callithrix jacchus). Thirteen marmosets were trained on a battery of behavioural tasks that were conducted at regular intervals before and after surgery. All received unilateral 6-OHDA lesions to the medial forebrain bundle. Seven animals were then given an additional N-methyl-d -aspartate lesion of the ipsilateral subthalamic nucleus, whereas the remaining six animals received a variety of control or sham lesions to the nucleus. The 6-OHDA lesions induced a strong ipsilateral bias in head position; mild–moderate ipsilateral rotation spontaneously and after injection of saline or amphetamine; and contralateral rotation after injection of apomorphine. Hemineglect was evident as delayed initiation of reaches on the contralateral side on the staircase reaching task. Additional subthalamic lesions significantly reversed the bias in head position from ipsilateral to contralateral and decreased neglect as evidenced by improved latencies to initiate reaching on the contralateral side at the staircase. However, deficits in skilled movements persisted in the subthalamic nucleus lesion group in that they did not complete the staircase task any faster than the control group and remained impaired on another task which required reaching into tubes. These behavioural effects demonstrate that excitotoxic lesioning of the subthalamic nucleus can ameliorate some, but not all, parkinsonian-like deficits in the unilateral 6-OHDA lesioned marmoset. 相似文献
13.
Behavioral and electrophysiological methods were used to determine whether a transplant of dopamine-rich fetal tissue in striatum combined with an electrolytic lesion of the entopeduncular nucleus have additive effects in the unilaterally lesioned rat model for Parkinson's disease. The subjects were rats with the left substantia nigra lesioned with 6-hydroxydopamine (6-OHDA) and responding to systemic amphetamine with rotation toward the side of the lesion (ipsilateral rotation). The motor response to amphetamine was fractionated into six aspects, half reflecting the unilateral deafferentation in striatum and half representing those aspects of the response evoked in normal rats. After collection of baseline values, 25 rotators received a transplant of fetal ventral mesencephalic tissue in the left striatum and 20 received a transplant and, at the same time, an electrolytic lesion of the left entopeduncular nucleus. Testing for the motor response to amphetamine resumed after 4 weeks of recovery and continued at weekly intervals for 5 weeks. Upon completion of these tests, each rotator was implanted with multiple electrodes in the subthalamic nucleus. After recovery, multiunit responses to amphetamine and apomorphine were recorded from several electrodes in parallel during the motor response to the drugs. In rotators with transplant only, treatment with amphetamine evoked oral stereotypy and an attenuated ipsilateral rotation response. In rotators with combined transplant and entopeduncular lesion, ipsilateral rotation did not change or increased. Subthalamic responses to amphetamine and apomorphine were larger in rotators with combined transplant and entopeduncular lesion than in rotators with transplant alone. These findings indicate that the combination of transplant and pallidotomy in the 6-OHDA rat model for parkinsonism does not lead to additive benefits, an effect that may have been due to the nonselectivity of the electrolytic damage and/or of the lesion extending beyond the entopeduncular nucleus into the lateral hypothalamus. 相似文献
14.
Stimulation of the subthalamic nucleus enhances the release of dopamine in the rat substantia nigra 总被引:6,自引:0,他引:6
The release of dopamine in the substantia nigra and striatum was investigated in halothane anaesthetized rats by means of the push-pull cannula method. Electrical stimulation of the subthalamic nucleus produced a marked enhancement of dopamine release in the ipsilateral substantia nigra. This effect is likely to be mediated by subthalamic efferent neurons since the application of acetylcholine in the subthalamic nucleus produced a similar effect. A later decrease of dopamine release was always observed in the ipsilateral striatum and was attributed to the autoregulation mechanisms of nigro-striatal dopaminergic neurons. 相似文献
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The subthalamic nucleus is targeted for the treatment of Parkinson's disease. Unilateral lesions improve some aspects of parkinsonism but produce postural abnormalities in animal models but the exact pathways producing these effects remain to be defined. Using a battery of tests we evaluated the effects of lesioning one of the two major subthalamic targets, the substantia nigra pars reticulata in na?ve and 6-OHDA lesioned rats. Lesions targeting the mid-substantia nigra pars reticulata resulted in acute tonic-clonic seizures and intense contralateral rotational asymmetry. During the first month after substantia nigra pars reticulata lesions there was normalisation of the ipsilateral head position bias induced by unilateral 6-OHDA lesions, significant contralateral body axis bias but no significant alteration of apomorphine induced rotation and sensorimotor neglect in 6-OHDA lesioned rats. Combined with our previous data, this suggests that subthalamic projections via the substantia nigra pars reticulata are important in seizures and postural behaviours. Therefore unilateral subthalamotomy probably induces postural deficits in hemiparkinsonian animals via projections involving the substantia nigra pars reticulata. This has implications for patients undergoing subthalamotomy for treatment of Parkinson's disease. 相似文献
16.
Sanchez B Relova JL Gallego R Ben-Batalla I Perez-Fernandez R 《Journal of neuroscience research》2009,87(3):723-732
It has previously been demonstrated that 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] administration, whether in cell cultures or in vivo to rats, increases glial cell line-derived neurotrophic factor (GDNF) expression levels, suggesting that this hormone may have beneficial effects in neurodegenerative disorders. This study was carried out to explore the effects of 1,25(OH)(2)D(3) administration in a 6-OHDA-lesioned rat model of Parkinson's disease on GDNF and tyrosine hydroxylase (TH) expression in substantia nigra (SN) and striatum. Two groups of animals received 1,25(OH)(2)D(3) intraperitoneally, the first group 7 days before the unilateral injection of 6-OHDA into the medial forebrain bundle (MFB) and the second group 21 days (days 21-28) after the unilateral injection of 6-OHDA. Animals of both groups were sacrificed on day 28. In addition, two other groups received a unilateral injection of either saline or 6-OHDA into the MFB. Rats were killed, and the SN and striatum were then removed for GDNF and TH determination. Striatal GDNF protein expression was increased on the ipsilateral with respect to the contralateral side after 6-OHDA injection alone as well as in 1,25(OH)(2)D(3)-treated rats before or after 6-OHDA administration. As expected, 6-OHDA injection induced an ipsilateral decrease in TH-immunopositive neuronal cell bodies and axonal terminals in the SN and striatum. However, treatment with 1,25(OH)(2)D(3) before and after 6-OHDA injection partially restored TH expression in SN. These data suggest that 1,25(OH)(2)D(3) may help to prevent dopaminergic neuron damage. 相似文献
17.
目的探讨高频电刺激丘脑底核对帕金森病(PD)大鼠黑质致密部(SNc)神经元的保护作用及机制。方法将40只SD大鼠随机分为3组,正常对照组10只,模型组及刺激组各15只。模型组及刺激组大鼠于脑内侧前脑束注射6-羟基多巴胺(6-OHDA)制备大鼠偏侧PD模型,刺激组大鼠丘脑底核区植入刺激电极实施高频电刺激(130Hz),对三组动物的行为学、SNc神经元的形态学改变进行观察和分析。结果术后2、4周时,刺激组SNc神经元凋亡的阳性率分别为(39.98±12.11)%和(41.12±9.23)%,模型组则为(61.74±7.82)%和(67.12±10.23)%;两组比较,差异有统计学意义(P<0.05)。术后2、4周时,刺激组Bcl-2/Bax比值为0.84±1.01和0.88±0.81,模型组则为0.39±0.15和0.30±0.58;两组比较,差异有统计学意义(P<0.05)。结论高频刺激丘脑底核对PD大鼠黑质SNc神经元有保护作用,其机制可能与改变了SNc区神经递质的分布和代谢有关。 相似文献
18.
N-terminal tripeptide of IGF-1 (GPE) prevents the loss of TH positive neurons after 6-OHDA induced nigral lesion in rats 总被引:5,自引:0,他引:5
The effect of the N-terminal tripeptide of insulin-like growth factor (IGF)-1, glycine-proline-glutamate (GPE), as a neuroprotective agent for nigro-striatal dopaminergic neurons was examined in the present study using a rat model of Parkinson's disease. A unilateral nigro-striatal lesion was induced in rats by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB). GPE (3 microgram) or its vehicle was administered intracerebroventricularly (i.c.v.) 2 h after the 6-OHDA lesion. Tyrosine-hydroxylase (TH) immunohistochemistry in the substantia nigra compacta (SNc) and the striatum were examined 2 weeks after the lesion. Following 6-OHDA injection, the number of TH immunopositive neurons in the ipsilateral SNc was reduced. The density of TH immunostaining was also reduced in the ipsilateral SNc and the striatum. Treatment with a single dose of GPE (n=9) significantly prevented the loss of TH immunopositive neurons (p<0. 001) and restored the TH immunoreactivity in both the SNc and the striatum compared with the vehicle control group (n=9, p<0.001). The results suggest that GPE showed promise as a potential treatment for Parkinson's disease. 相似文献
19.
Rats received fetal dopaminergic neuronal grafts in the striatum and/or substantia nigra ipsilateral to a 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle (MFB). Dopaminergic grafts in the striatum substantially and significantly reduced turning elicited by the selective D1 agonist SKF 38393, but did not reduce turning elicited by the selective D2 agonist LY 171555. Thus, reduced turning in such grafted animals in response to non-selective dopaminergic agonists may be the result of diminished D1 supersensitivity. Fetal dopaminergic grafts in the ipsilateral substantia nigra (SN) did not augment the decreases in turning produced by concomitant ipsilateral dopaminergic grafts in the striatum in response to SKF 38393. LY 171555, D-amphetamine or L-DOPA. Dopaminergic grafts in the SN increased, while dopaminergic grafts in the striatum or in striatum and SN decreased, the facilitatory effect of D-amphetamine on rotation elicited by subsequent injection of dopamine agonists. 相似文献
20.
丘脑底核高频电刺激对大鼠纹状体多巴胺代谢影响的研究 总被引:3,自引:0,他引:3
目的研究丘脑底核(STN)高频电刺激(HFS)对大鼠纹状体多巴胺(DA)代谢的影响。方法给予正常大鼠一侧STN-HFS,应用微透析观察其对纹状体DA及其代谢产物的影响,应用免疫组化观察其对黑质DA能神经元的影响。结果微透析检测发现刺激侧纹状体DA代谢产物明显增高(P<0.05),DA水平无变化(P>0.05);免疫组化检测发现刺激组和对照组酪氨酸羟化酶(TH)阳性神经元数量无差异(损毁侧分别为24.00±6.81、23.43±5.49,P>0.05)。结论STN-HFS可能通过影响黑质-纹状体DA代谢发挥作用,STN-HFS对黑质DA能神经元可能无保护作用。 相似文献