caa a22 4500 475787897 CHVBK 20180406123704.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1007/s004149900095 doi (NATIONALLICENCE)springer-10.1007/s004149900095 The role of tumor necrosis factor-α in diffuse axonal injury following fluid-percussive brain injury in rats [Elektronische Daten] [T. Kita, T. Tanaka, N. Tanaka, Y. Kinoshita] The immunolocalization of tumor necrosis factor-α (TNFα) after diffuse axonal injury (DAI) is demonstrated using a midline fluid percussion rat model (moderate brain injury of 1000 mm Hg was generated) and the effects of TNFα on the axolemmal permeability using horseradish peroxidase as a tracer. In addition, the accumulation of β-amyloid precursor protein (β-APP) was investigated, which has recently been shown to be a reliable marker for the diagnosis of DAI in cases with fatal head injury. TNFα levels in brain tissues from the impact site and the cortex including the corpus callosum, gradually increased during the first 1 h, rose to a maximal elevation at 3 h, gradually decreased at 6 h and decreased further at 24 h. Horseradish peroxidase (HRP) tracer experiments revealed that primary axonal damage appeared as early as 15 min after impact but rapidly recovered and that 1 h after impact, secondary axonal damage occurred in the corpus callosum and the brain stem. By immunoelectron microscopy it was seen that β-APP accumulated in the axon from 1 h after impact demonstrating that there was functional axonal damage. TNFα reactions were detected in the lysosomes of microglia 30 min after impact and 1 h after impact these reactions were mainly detected in the glial cells (such as microglia, astrocytes and oligodendrocytes) in the corpus callosum and the brain stem. It is generally accepted that TNFα directly induces primary demyelination and oligodendrocyte apoptosis. Therefore, TNFα conveyed from the microglial cells is one cofactor contributing to the formation of the delayed axonal damage observed at these sites. The present study suggests that TNFα conveyed from the glial cells may contribute to the pathogenic mechanism of DAI formation following fluid percussive brain injury. Springer-Verlag Berlin Heidelberg, 2000 Key words Traumatic head injury nationallicence Diffuse axonal ¶injury nationallicence Tumor necrosis factor-α nationallicence β-Amyloid precursor ¶protein nationallicence Fluid percussion device nationallicence Glial cell nationallicence Kita T. Department of Forensic Medicine, School of Medicine, University of Occupational and Environmental Health, Yahata Nishiku, Kitakyushu 807, Japan e-mail: kita@med.uoeh-u.ac.jp, JP aut Tanaka T. Department of Forensic Medicine, School of Medicine, University of Occupational and Environmental Health, Yahata Nishiku, Kitakyushu 807, Japan e-mail: kita@med.uoeh-u.ac.jp, JP aut Tanaka N. Department of Forensic Medicine, School of Medicine, University of Occupational and Environmental Health, Yahata Nishiku, Kitakyushu 807, Japan e-mail: kita@med.uoeh-u.ac.jp, JP aut Kinoshita Y. Department of Neurosurgery, School of Medicine, University of Occupational and Environmental Health, Yahata Nishiku, Kitakyushu 807, Japan, JP aut https://doi.org/10.1007/s004149900095 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s004149900095 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kita T. Department of Forensic Medicine, School of Medicine, University of Occupational and Environmental Health, Yahata Nishiku, Kitakyushu 807, Japan e-mail: kita@med.uoeh-u.ac.jp, JP aut NATIONALLICENCE 700 1- Tanaka T. Department of Forensic Medicine, School of Medicine, University of Occupational and Environmental Health, Yahata Nishiku, Kitakyushu 807, Japan e-mail: kita@med.uoeh-u.ac.jp, JP aut NATIONALLICENCE 700 1- Tanaka N. Department of Forensic Medicine, School of Medicine, University of Occupational and Environmental Health, Yahata Nishiku, Kitakyushu 807, Japan e-mail: kita@med.uoeh-u.ac.jp, JP aut NATIONALLICENCE 700 1- Kinoshita Y. Department of Neurosurgery, School of Medicine, University of Occupational and Environmental Health, Yahata Nishiku, Kitakyushu 807, Japan, JP aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer