Here we show that A1 reactive astrocytes are induced by activated microglia. A1s lose most normal astrocyte functions but gain a new neurotoxic function, rapidly killing neurons and mature differentiated oligodendrocytes. We show A1s rapidly form in vivo after CNS injury and are highly present in many human neurodegenerative diseases. Lastly we show that inhibition of A1 reactive astrocyte formation after acute CNS injury, prevents death of axotomized neurons. Thus A1 reactive astrocytes are harmful, contributing to neuron death after acute CNS injury. Understanding the multidimensional roles of reactive astrocytes has great potential to contribute to development of new treatment strategies to reduce CNS cell loss and neurological impairment after acute CNS injury as well as in neurodegenerative diseases.
