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Chunk #1 — Introduction

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Neurotoxic reactive astrocytes are induced by activated microglia.
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We previously purified and gene profiled reactive astrocytes from mice treated either with a systemic injection of lipopolysaccharide (LPS), or received middle cerebral artery occlusion to induce ischemia5. We found neuroinflammation and ischemia induced two different types of reactive astrocytes that we termed “A1” and “A2” respectively (in analogy to the “M1”/“M2” macrophage nomenclature, a nomenclature under current refinement because macrophages clearly can display more than two polarization states8,9). A1s highly up-regulate many classical complement cascade genes previously shown to be destructive to synapses, so we postulated that A1s might be harmful. In contrast, A2s up-regulated many neurotrophic factors and we thus postulated that A2s are protective. Consistent with this latter possibility, previous studies have provided evidence that reactive astrocytes induced by ischemia promote CNS recovery and repair1,10,11.