Title : Astrocytes have neuroimmunological function in the stab wound mouse brain
Abstract:
Background: Some glial cells such as astrocytes and microglial cells activated when the traumatic injury occurred to the brain. After the stab wound to the mouse brain, those glial cells proliferate and secrete some of the inflammatory cytokines, however the functional role of these activations are still unknown.
Objective: We have been analyzing the functional role of reactive glial cells in the mouse brain with stab wound injury and found that some of the molecules are concerning to the blood brain barrier (BBB) recovery from the break down caused by the brain injury. Since extracellular matrix protein tenascin-C (TN-C), one of the water channels in astrocytes aquaporin 4 (AQP4), and the inflammatory cytokine inducer osteopontin (OPN) expression levels are upregulated according to the astrocyte reactivation, we analyzed functional roles in reactive astrocytes.
Methods: We used gene deficient mice (TN-C/KO, AQP4/KO, OPN/KO) with stab wound injury on the cerebral cortex for the analysis. For the immuno-fluorescent analysis on the brain sections, antibodies against bromo-deoxy-uridine (BrdU) for proliferating cells, GFAP for astrocytes, Iba1 for microglial cells, and IgG for BBB breakdown were used. DNA microarray analysis was performed with RNA extracted from either AQP4/KO or WT mice 3 days after the stab wound site.
Results & Conclusions: We found that reactivation of astrocytes in the injured brain, TN-C is required for BBB recovery from the breakdown caused by stab wound in the brain. Additionally, AQP4 is not only the water channel but also might have a neuroimmunological function in reactive astrocytes around injured site and we hypothesized that integrin a9 and b1 found to be the receptors against OPN in the injured brain.
Audience Take Away
- Brain has not only neurons but also glial cells such as astrocytes and microglial cells
- What are the glial cells doing in the brain
- Glial cells become active when the brain has injury so that those cells could be the target for neuro-regenerations or cure the neurodegenerative diseases
- Neuroinflammation might be an important situation after the brain injury or disease