||Okada S, Nakamura M, Katoh H, Miyao T, Shimazaki T, Yamane J, Ishii K, Yoshimura A, Iwamoto Y, Toyama Y, and Okano H, Conditional ablation of Stat3/Socs3 discloses the dual role for reactive astrocytes after spinal cord injury. , Nature medicine, 12(7):829-34, 2006.07.
||Masamitsu Hara, Kazu Kobayakawa, Yasuyuki Ohkawa, Hiromi Kumamaru, Kazuya Yokota, Takeyuki Saito, Ken Kijima, Shingo Yoshizaki, Katsumi Harimaya, Yasuharu Nakashima, Seiji Okada, Interaction of reactive astrocytes with type i collagen induces astrocytic scar formation through the integrin-N-cadherin pathway after spinal cord injury, Nature Medicine, 10.1038/nm.4354, 23, 7, 818-828, 2017.07, Central nervous system (CNS) injury transforms naive astrocytes into reactive astrocytes, which eventually become scar-forming astrocytes that can impair axonal regeneration and functional recovery. This sequential phenotypic change, known as reactive astrogliosis, has long been considered unidirectional and irreversible. However, we report here that reactive astrocytes isolated from injured spinal cord reverted in retrograde to naive astrocytes when transplanted into a naive spinal cord, whereas they formed astrocytic scars when transplanted into injured spinal cord, indicating the environment-dependent plasticity of reactive astrogliosis. We also found that type I collagen was highly expressed in the spinal cord during the scar-forming phase and induced astrocytic scar formation via the integrin-N-cadherin pathway. In a mouse model of spinal cord injury, pharmacological blockade of reactive astrocyte-type I collagen interaction prevented astrocytic scar formation, thereby leading to improved axonal regrowth and better functional outcomes. Our findings reveal environmental cues regulating astrocytic fate decisions, thereby providing a potential therapeutic target for CNS injury..
||Kumamaru H, Ohkawa Y, Saiwai H, Yamada H, Kubota K, Kobayakawa K, Akashi K, Okano H, Iwamoto Y, Okada S*. , Direct isolation and RNA-Seq reveal environment-dependent properties of engrafted neural stem/progenitor cells., Nature Communications., 2012.10.
||Kobayakawa K, Kumamaru H, Saiwai H, Kubota K, Ohkawa Y, Kishimoto J, Yokota K, Ideta R, Shiba K, Tozaki-Saitoh H, Inoue K, Iwamoto Y, Okada S*, Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans., Science Translational Medicine, 2014.10.
||Yokota K, Kobayakawa K, Kubota K, Miyawaki A, Okano H, Ohkawa Y, Iwamoto Y, Okada S*, Engrafted neural stem/progenitor cells promote functional recovery through interactive synaptic reorganization with spared hos neurons after spinal cord injury., Stem Cell Reports., 2015.07.
||Saiwai H, Ohkawa Y, Yamada H, Kumamaru H, Harada A, Okano H, Yokomizo T, Iwamoto Y, Okada S*, The LTB4-BLT1 axis mediates neutrophils infiltration and secondary injury in experimental spinal cord injury., American Journal of Pathology., 2010.04.
||Okada S, Ishii K, Yamane J, Iwanami A, Ikegami T, Iwamoto Y, Nakamura M, Miyoshi H, Okano HJ, Contag CH, Toyama Y, and Okano H., In vivo imaging of engrafted neural stem cells: its application inevaluating the optimal timing of transplantation for spinal cord injury. , The FASEB Journal, 10.1096/fj.05-4082fje, 19, 11, 1839-+, 19(13):1839-41, 2005.12.
||Yokota K, Kobayakawa K, Saito T, Hara M, Okazaki K, Ishihara K, Yoshida S, Kijima K, Ohkawa Y, Kubo A, Iwamoto Y, Okada S*, Periosting promotes scar formation through the interaction between pericytes and infiltrating monocytes/macrophages after spinal cord injury., American Journal of Pathology, 2016.12.