脑缺血性卒中小鼠模型焦虑样行为过程中高水平NGF

Juliana Gonçalves de Araújo Fernandes , Edna Constanza Gómez Victoria , Eliana Cristina de Brito Toscano , Rodrigo Novaes Ferreira , Daniele Gonçalves Silva , Bruna da Silva Oliveira , Aline Mansueto Mourão , Vinícius Sousa Pietra Pedroso , Antônio Lúcio Teixeira , Aline Silva de Miranda , Milene Alvarenga Rachid
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引用次数: 3

摘要

中风后的神经精神障碍,包括抑郁和焦虑,通常与长期残疾有关。神经营养因子在许多神经退行性疾病和神经精神疾病的病理生理中起着重要作用。在目前的研究中,我们研究了缺血后14天神经营养因子在卒中相关行为和病理改变中的潜在参与。方法采用双侧颈总动脉闭塞(BCCAo)诱导C57BL/6小鼠短暂性全脑缺血。诱导后14天每天进行神经学评估。进行开阔场(OF)和高架加迷宫(EPM)试验。行为学实验结束后,取假手术小鼠和缺血小鼠的脑组织,用ELISA法检测裂解型caspase-3以及脑源性神经营养因子(BDNF)、胶质细胞系源性神经营养因子(GDNF)和神经生长因子(NGF)的组织病理学和免疫标记。结果缺血大鼠表现出焦虑样行为和组织病理学改变,主要表现为额叶皮层形成半暗带包围的小坏死腔和神经空泡化,海马神经元缺血,中脑胶质变。免疫组化观察到半暗带部分caspase-3阳性神经元。与假动物相比,BCCAo小鼠的大脑中发现了更高水平的NGF。两组均检测到相似浓度的BDNF和GDNF。结论NGF参与实验性脑缺血再灌注诱导后14天的焦虑样行为。
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High levels of NGF during anxiety-like behavior in a murine model of brain ischemic stroke

Purpose

Neuropsychiatric disorders following stroke, including depression and anxiety, are often associated with long-term disability. Neurotrophic factors play an important role in the pathophysiology of many neurodegenerative and neuropsychiatric disorders. In the current study, we investigated a potential participation of neurotrophic factors in stroke-associated behavioral and pathological changes 14 days after ischemia.

Methods

Transient global cerebral ischemia was induced by bilateral occlusion of common carotid arteries (BCCAo) in C57BL/6 mice. Neurological evaluation was performed daily up to 14 days after induction. The Open Field (OF) and Elevated Plus Maze (EPM) tests were performed. After behavioral tests, brains from sham and ischemic mice were removed and processed to evaluate histopathology and immunomarcation for cleaved caspase-3 as well as the neurotrophic factors brain-derived neurotrophic factor (BDNF), glial cell line derived neurotrophic factor (GDNF), and neural growth factor (NGF) by ELISA.

Results

Ischemic animals presented anxiety-like behavior and histopathological alterations mainly characterized by formation of small necrotic cavities surrounded by penumbra zone and neuropil vacuolation in the frontal cortex, ischemic neurons in the hippocampus and gliosis in the midbrain. Some immunopositive neurons for cleaved caspase-3 were observed in the penumbra by immunohistochemical analysis. Higher levels of NGF were found in the brain of BCCAo mice compared with sham animals. Similar concentrations of BDNF and GDNF were detected in both groups.

Conclusion

Our results suggested the participation of NGF in anxiety-like behavior at 14 days after induction of experimental cerebral ischemia and reperfusion.

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期刊介绍: Neurology, Psychiatry & Brain Research publishes original papers and reviews in biological psychiatry, brain research, neurology, neuropsychiatry, neuropsychoimmunology, psychopathology, psychotherapy. The journal has a focus on international and interdisciplinary basic research with clinical relevance. Translational research is particularly appreciated. Authors are allowed to submit their manuscript in their native language as supplemental data to the English version. Neurology, Psychiatry & Brain Research is related to the oldest German speaking journal in this field, the Centralblatt fur Nervenheilkunde, Psychiatrie und gerichtliche Psychopathologie, founded in 1878. The tradition and idea of previous famous editors (Alois Alzheimer and Kurt Schneider among others) was continued in modernized form with Neurology, Psychiatry & Brain Research. Centralblatt was a journal of broad scope and relevance, now Neurology, Psychiatry & Brain Research represents a journal with translational and interdisciplinary perspective, focusing on clinically oriented research in psychiatry, neurology and neighboring fields of neurosciences and psychology/psychotherapy with a preference for biologically oriented research including basic research. Preference is given for papers from newly emerging fields, like clinical psychoimmunology/neuroimmunology, and ideas.
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