Kumari Rita, Kumar J B Senthil, Luthra Pratibha Mehta
Neuropharmaceutical Research Laboratory, Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi 110007, India.
Neuropharmaceutical Research Laboratory, Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi 110007, India.
Neurosci Lett. 2015 Mar 4;589:191-5. doi: 10.1016/j.neulet.2014.12.030. Epub 2014 Dec 17.
The preoperative neuroprotective effect of the 7-nitroindazole (7-NI) in 6-hydroxydopamine (6-OHDA) induced unilateral male animal models of Parkinson's disease (PD) has been widely reported. However, the therapeutic approach to PD pathology would be closely associated with the post-lesion treatment by 7-NI in 6-OHDA-induced bilateral model. Also, there is a scarcity of data on neuroprotective effect of 7-NI in PD in females. We have studied the neuroprotective effects of 7-NI in 6-OHDA-induced bilaterally lesioned female rats after short-term post-lesion treatment. Sprague-Dawley female rats with bilateral intraventricular injection of either 6-OHDA (10.5μg) (n=8-11/group) or saline (sham; n=8/group) at substantia nigra (SN) were provided with 7-NI (30mg/kg/day) intraperitoneal, once a day during the 3 consecutive days of short term treatment. 6-OHDA lesioned animals developed the motor and non-motor deficits, which were evaluated by behavioral and neuro-biochemical tests from the substantia nigra. Post-lesion administration of 7-NI reduced the motor deficits induced by 6-OHDA in the behavioral tasks such as Rota rod, open field test and forced swim test. Simultaneously, the dopamine levels were restored by 7-NI in post lesion animals up to 76% in comparison to 6-OHDA lesioned animals (23%). Furthermore, antioxidant-like effect of 7-NI was observed in lipid peroxidation, catalase, superoxide dismutase, and reduced glutathione tests. Conclusively, the present study showed that early postoperative administration of 7-NI attenuates the motor deficits induced by 6-OHDA in bilaterally lesioned female rat model of PD.
7-硝基吲唑(7-NI)在6-羟基多巴胺(6-OHDA)诱导的单侧雄性帕金森病(PD)动物模型中的术前神经保护作用已被广泛报道。然而,PD病理学的治疗方法与7-NI在6-OHDA诱导的双侧模型中的损伤后治疗密切相关。此外,关于7-NI对雌性PD神经保护作用的数据较少。我们研究了7-NI在6-OHDA诱导的双侧损伤雌性大鼠损伤后短期治疗中的神经保护作用。将双侧脑室内注射6-OHDA(10.5μg)(每组8-11只)或生理盐水(假手术组;每组8只)至黑质(SN)的Sprague-Dawley雌性大鼠在短期治疗的连续3天内每天腹腔注射一次7-NI(30mg/kg/天)。6-OHDA损伤的动物出现运动和非运动缺陷,通过行为和神经生化测试对黑质进行评估。损伤后给予7-NI可减少6-OHDA在行为任务如转棒试验、旷场试验和强迫游泳试验中诱导的运动缺陷。同时,与6-OHDA损伤动物(23%)相比,7-NI使损伤后动物的多巴胺水平恢复高达76%。此外,在脂质过氧化、过氧化氢酶、超氧化物歧化酶和还原型谷胱甘肽测试中观察到7-NI具有抗氧化样作用。总之,本研究表明,术后早期给予7-NI可减轻6-OHDA在双侧损伤雌性PD大鼠模型中诱导的运动缺陷。