Masaya Tachibana1, Ikuko Mohri1, Ikuko Hirata1, Ayano Kuwada1, Shihoko Kimura-Ohba2, Kuriko Kagitani-Shimono1, Hiroaki Fushimi3, Takeshi Inoue4, Masashi Shiomi4, Yukio Kakuta5, Makoto Takeuchi6, Shigeo Murayama7, Masahiro Nakayama6, Keiichi Ozono2, Masako Taniike8. 1. Department of Child Development, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan; Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. 2. Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. 3. Department of Pathology, Osaka General Medical Center, Osaka, Japan. 4. Department of Pathology, Osaka City General Hospital, Osaka, Japan. 5. Department of Pathology, Japan Organization of Occupational Health and Safety, Yokohama Rosai Hospital, Yokohama, Kanagawa, Japan. 6. Division of Clinical Laboratory Medicine and Anatomic Pathology, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan. 7. Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. 8. Department of Child Development, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan; Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: masako@kokoro.med.osaka-u.ac.jp.
Abstract
BACKGROUND: Influenza-associated encephalopathy (IAE) is one of the most serious CNS complications of an influenza virus infection, with unclear pathophysiology. Clasmatodendrosis is a complex of morphological changes in astrocytes characterized by fragmentation of the distal processes and swollen cell bodies. Although pathologists in Japan have long been aware of the presence of clasmatodendrosis in IAE brains, no details of the phenomenon have been published to date. We aimed to confirm the existence, and characterize the spatial distribution of clasmatodendrosis in postmortem IAE brains. METHODS: Autopsied brains from 7 patients with IAE and 8 non-IAE subjects were examined immunohistochemically. In addition, immunofluorescent staining and electron microscopy were performed. RESULTS: Clasmatodendrosis was present in all examined regions of the IAE brains, but none of the control brains. Fragmented processes of astrocytes in IAE brains were closely adjacent to synapses on the dendritic spines, with the fragmentation especially prominent in the cerebellar molecular layer. In addition, the clasmatodendrotic astrocytes were negative for autophagy markers. Furthermore, whereas aquaporin 4 was predominantly detected in the perivascular endfeet of astrocytes in the control brains, its primary localization site shifted to the fragmented perisynaptic processes in the IAE brains. CONCLUSION: Clasmatodendrosis was distributed diffusely in the IAE brains in close association with synapses, and was not caused by astrocyte autophagy. Clasmatodendrosis may be a suggestive pathological feature of IAE.
BACKGROUND:Influenza-associated encephalopathy (IAE) is one of the most serious CNS complications of an influenza virus infection, with unclear pathophysiology. Clasmatodendrosis is a complex of morphological changes in astrocytes characterized by fragmentation of the distal processes and swollen cell bodies. Although pathologists in Japan have long been aware of the presence of clasmatodendrosis in IAE brains, no details of the phenomenon have been published to date. We aimed to confirm the existence, and characterize the spatial distribution of clasmatodendrosis in postmortem IAE brains. METHODS: Autopsied brains from 7 patients with IAE and 8 non-IAE subjects were examined immunohistochemically. In addition, immunofluorescent staining and electron microscopy were performed. RESULTS: Clasmatodendrosis was present in all examined regions of the IAE brains, but none of the control brains. Fragmented processes of astrocytes in IAE brains were closely adjacent to synapses on the dendritic spines, with the fragmentation especially prominent in the cerebellar molecular layer. In addition, the clasmatodendrotic astrocytes were negative for autophagy markers. Furthermore, whereas aquaporin 4 was predominantly detected in the perivascular endfeet of astrocytes in the control brains, its primary localization site shifted to the fragmented perisynaptic processes in the IAE brains. CONCLUSION: Clasmatodendrosis was distributed diffusely in the IAE brains in close association with synapses, and was not caused by astrocyte autophagy. Clasmatodendrosis may be a suggestive pathological feature of IAE.
Authors: András Lakatos; James P O'Callaghan; Gabor C Petzold; Alberto Serrano-Pozo; Christian Steinhäuser; Andrea Volterra; Giorgio Carmignoto; Carole Escartin; Elena Galea; Amit Agarwal; Nicola J Allen; Alfonso Araque; Luis Barbeito; Ari Barzilai; Dwight E Bergles; Gilles Bonvento; Arthur M Butt; Wei-Ting Chen; Martine Cohen-Salmon; Colm Cunningham; Benjamin Deneen; Bart De Strooper; Blanca Díaz-Castro; Cinthia Farina; Marc Freeman; Vittorio Gallo; James E Goldman; Steven A Goldman; Magdalena Götz; Antonia Gutiérrez; Philip G Haydon; Dieter H Heiland; Elly M Hol; Matthew G Holt; Masamitsu Iino; Ksenia V Kastanenka; Helmut Kettenmann; Baljit S Khakh; Schuichi Koizumi; C Justin Lee; Shane A Liddelow; Brian A MacVicar; Pierre Magistretti; Albee Messing; Anusha Mishra; Anna V Molofsky; Keith K Murai; Christopher M Norris; Seiji Okada; Stéphane H R Oliet; João F Oliveira; Aude Panatier; Vladimir Parpura; Marcela Pekna; Milos Pekny; Luc Pellerin; Gertrudis Perea; Beatriz G Pérez-Nievas; Frank W Pfrieger; Kira E Poskanzer; Francisco J Quintana; Richard M Ransohoff; Miriam Riquelme-Perez; Stefanie Robel; Christine R Rose; Jeffrey D Rothstein; Nathalie Rouach; David H Rowitch; Alexey Semyanov; Swetlana Sirko; Harald Sontheimer; Raymond A Swanson; Javier Vitorica; Ina-Beate Wanner; Levi B Wood; Jiaqian Wu; Binhai Zheng; Eduardo R Zimmer; Robert Zorec; Michael V Sofroniew; Alexei Verkhratsky Journal: Nat Neurosci Date: 2021-02-15 Impact factor: 24.884