Ikeshima-kataoka, M Furukawa, S Inui, M Imamura, Y Honjyo and M Yasui
Waseda University, Japan
Keio University School of Medicine, Japan
Scientific Tracks Abstracts: J Neurol Neurophysiol
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 the 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 on the regeneration of the CNS, we have been to analyze the 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 the 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 the 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 the injured brain using AQP4-deficient mice (AQP4/KO) compared to the wild type mouse (WT) brain. To label the proliferating cells, Bromodeoxyuridine (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 an antibody against BrdU for proliferating cells, glial fibrillary acidic protein (GFAP) for astrocytes, or Iba1 for microglial cells. Furthermore, we also used DNA microarray analysis with RNA extracted from either AQP4/KO or WT mice on 3 days after the injury around stab wound site compared to the brain without stab wound brain sections by laser microdissection method. We found out that most of the genes in the top 20 highly upregulated were related to the immune system or inflammatory cascades. Especially, an expression level of one of the inflammatory cytokine inducer, osteopontin (OPN) and its receptors was most drastically enhanced in injured mouse brain at day after 3 of stab wound compared to without wounding, while it was slightly upregulated in AQP4/KO mice. From these results, we hypothesized that AQP4 might have not only the water channel role but also have some neuroimmunological functional roles in reactive astrocytes in injured mouse brain correlated with OPN and with its receptors. We are now analyzing reactive astrocytes in OPN-deficient mice to elucidate the functional role of OPN in the injured brain
Ikeshima-Kataoka was graduated from Keio University School of Medicine (Department of Microbiology) and got PhD on the functional analysis of three calmodulin genes using transgenic mice. At the National Institute of Neuroscience as a postdoctoral fellow, research 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 an immunological team in Institute of DNA Medicine and focus on to neuroimmunological analysis in the 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 the injury site of the brain using microarray analysis. Now, using in vivo imaging system with the live mouse to analyze functional role of “reactive astrocytes” around injured brain at Waseda University, Faculty of Science and Engineering.
E-mail: hilocoikeshima@gmail.com
