Yamada M, Natsume A, Mata M, Oligino T, Goss J, Glorioso J, Fink D J
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Exp Neurol. 2001 Apr;168(2):225-30. doi: 10.1006/exnr.2000.7597.
Proximal axotomy in adult animals results in delayed death of motor neurons. Features characteristic of both necrosis and apoptosis have been described in motor neurons of the spinal cord following proximal avulsion of the ventral roots. We have previously demonstrated that a genomic herpes simplex virus (HSV)-based vector expressing the anti-apoptotic peptide Bcl-2 protects dopaminergic neurons of the substantia nigra from neurotoxin-induced apoptotic cell death and preserves the neurotransmitter phenotype of those cells. In this study we examined whether the same vector could protect adult rat lumbar motor neurons from cell death following proximal ventral root avulsion. Injection of the Bcl-2-expressing vector 1 week prior to root avulsion increased the survival of lesioned motor neurons, determined by retrograde Fluorogold labeling, by 50%. The Bcl-2-expressing vector did not preserve choline acetyltransferase neurotransmitter phenotype of the lesioned cells. These results shed light on the mechanism of cell death following axonal injury, and have implications for developing an effective treatment for the clinical problem of proximal root avulsion.
成年动物的近端轴突切断会导致运动神经元延迟死亡。在腹侧神经根近端撕脱后，脊髓运动神经元中已描述了坏死和凋亡的特征。我们之前已证明，一种基于基因组单纯疱疹病毒（HSV）的载体表达抗凋亡肽Bcl-2，可保护黑质多巴胺能神经元免受神经毒素诱导的凋亡性细胞死亡，并保留这些细胞的神经递质表型。在本研究中，我们检测了同一载体是否能保护成年大鼠腰段运动神经元免受近端腹侧神经根撕脱后的细胞死亡。在神经根撕脱前1周注射表达Bcl-2的载体，通过逆行荧光金标记确定，损伤的运动神经元存活率提高了50%。表达Bcl-2的载体未保留损伤细胞的胆碱乙酰转移酶神经递质表型。这些结果揭示了轴突损伤后细胞死亡的机制，并对开发针对近端神经根撕脱临床问题的有效治疗方法具有启示意义。
