Keio University School of Medicine, Japan

Title: Reactive Astrocyte has a Neuroimmunological Function in injured Mouse Brain


Dr. Ikeshima-Kataoka was graduated from Keio University School of Medicine (Department of Microbiology) and got Ph.D. on the functional analysis of three calmodulin genes using transgenic mice. At the National Institute of Neuroscience as a postdoctoral fellow, researched on the molecular mechanism of neuronal development using fly genetics. Then, promoted back to Keio University School of Medicine (Department of Neuroanatomy) and started to focus on to the “reactive astrocytes” in injured mouse brain. At Jikei University School of Medicine, joined to immunological team in Institute of DNA Medicine and focus on to neuroimmunological analysis in injured brain using knockout mice. Then, promoted back to Keio University School of Medicine (Department of Pharmacology and Neuroscience) and found that some important molecules are concerned in neuroimmunological functions around injury site of the brain using microarray analysis. Now, using in vivo imaging system with live mouse to analyze functional role of “reactive astrocytes” around injured brain at Waseda University, Faculty of Science and Engineering. 


In the central nervous system (CNS), some glial cells such as astrocytes and microglial cells become active to proliferate and secrete some of the inflammatory cytokines around lesion site when traumatic injury or inflammation occurred. However, it is still unclear for the functional role of those activated glial cells in the brain. To focus onto the regeneration of the CNS, we have been to analyze functional role of reactive glial cells in the brain with stab wound injury. As a brain injury model, stab wound using 27G needle was made on the mouse cerebral cortex from caudal to rostral axis. In the reactive astrocytes, one of the extracellular matrix molecule, tenascin-C (TN-C) is highly expressed, we analyzed TN-C functional role using TN-C-deficient mice (TN-C/KO) and found that TN-C is required for activation of astrocytes such as proliferating and induce secretion of some of the inflammatory cytokines in the injured brain and in the primary culture of astrocytes. Furthermore, TN-C has an important role for recovery of blood brain barrier (BBB) breakdown caused by stab wound in the brain. From these results, reactivation of astrocytes in the injured brain might have a functional role for BBB recovery in the CNS. On the other hand, since one of the water channels in the CNS aquaporin 4 (AQP4) is upregulated in activated astrocytes after the stab wound, we have analyzed AQP4 functional role in reactive astrocytes with injured brain using AQP4-deficient mice (AQP4/KO) compared to the wild type mouse (WT) brain. To label the proliferating cells, bromo-deoxy-uridine (BrdU) was used and that could be incorporated to the mice through the drinking water. Immuno-fluorescent staining analysis was performed on cardiac perfused mouse brain sections with