INSITU INJECTION OF KAINIC ACID - NEW METHOD FOR SELECTIVELY LESIONING NEURONAL CELL BODIES WHILE SPARING AXONS OF PASSAGE

INSITU INJECTION OF KAINIC ACID - NEW METHOD FOR SELECTIVELY LESIONING NEURONAL CELL BODIES WHILE SPARING AXONS OF PASSAGE
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DOI:
10.1002/cne.901800208
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发表时间:
1978-01-01
影响因子:
2.5
通讯作者:
KUHAR, MJ
KUHAR, MJ
中科院分区:
医学3区
文献类型:
--
作者:
COYLE, JT;MOLLIVER, ME;KUHAR, MJ

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采用亮场、组织荧光和电镜技术观察大鼠纹状体立体定向注射谷氨酸构象限制性类似物桂酸后的形态学变化。对盐酸盐注射的神经病理反应发生在两个不同的阶段。第一阶段,纹状体内禀神经元在注射后48小时内快速变性;其特征是细胞质nissl -物质的连续丢失(染色质溶解),核周收缩,核染色质聚集,最后核膜破坏。注射后1 - 3周,第二阶段的特征是灰质中星形胶质细胞的显著增殖,灰质原来是由神经元组成的。海碱盐注入纹状体中几个神经元的损失区域呈近似球形,其程度与海碱盐注入量呈非线性相关。由于固有神经元的死亡和过程的丧失,注射纹状体的神经pil明显被破坏。然而,组织荧光显微镜显示,从黑质伸出的多巴胺能轴突在海碱盐注射的纹状体中没有退化;EM研究表明,穿越纹状体的皮质纤维也不受盐的影响。许多突触前钮扣(可能是外源性的)在注射后10天仍完好无损;突触后元件的亲渗痕迹仍然附着在这些钮扣上。病变区域可见大量吞噬星形细胞。脑内原位注射kainic酸导致注射区域内具有胞体的神经元选择性变性,但保留了该区域外核周产生的轴突,但穿过或终止于注射区域。原位注射kainic酸是一种新技术,可用于选择性脑损伤,可用于检查神经元连接。
The morphologic sequelae following stereotaxic injection into the rat striatum of kainic acid, a conformationally restricted analog of glutamate, were examined by means of bright field, histofluorescence and EM techniques. The neuropathologic response to kainate injection occurs in 2 distinct phases. In the 1st phase, the intrinsic neurons of the striatum undergo a rapid degeneration during the first 48 h after injection; this is characterized by the sequential loss of cytoplasmic Nissl-substance (chromatolysis), shrinkage of the perikarya, clumping of the nuclear chromatin and finally disruption of the nuclear membrane. Between 1 and 3 wk after injection, a marked proliferation of astrocytes in the gray matter formerly populated by neurons characterizes the 2nd phase. The region of several neuronal loss in the kainate injected striatum is approximately spherical in shape, and its extent is non-linearly related to the amount of kainate injected. The neuropil of the injected striatum is markedly disrupted due to the death of intrinsic neurons and loss of their processes. Yet, histofluorescence microscopy demonstrates that the dopaminergic axons projecting from the substantia nigra do not degenerate in the kainate injected striatum; EM studies indicate that corticofugal fibers traversing the striatum are also unaffected by kainate. Many presynaptic boutons, presumably of extrinsic origin, are intact up to 10 days after injection; osmophilic vestiges of postsynaptic elements remain adherent to these boutons. Numerous phagocytic astrocytes are observed throughout the lesioned area. In situ injection of kainic acid in brain causes a selective degeneration of neurons with cell bodies in the area of the injection but spares axons that arise from perikarya outside the region but pass through or terminate in the injected area. In situ injection of kainic acid is a new technique for making selective brain lesions that will be useful for examining neuronal connectivity.