CILIARY NEUROTROPHIC FACTOR STIMULATES ASTROGLIAL HYPERTROPHY IN-VIVOAND IN-VITRO

After insult or trauma, astrocytes become activated and endeavor to re store the brain's delicately balanced microenvironment. An index of th eir activated state is that they become enlarged or hypertrophic. Cili ary neurotrophic factor (CNTF), a member of the alpha helical family o f cytokines, is synthesized by astrocytes and is generally regarded to be an autocrine and paracrine injury signal. To determine whether CNT F might be an endogenous signal that stimulates astrocyte hypertrophy in vivo, we intracerebrally injected 200 ng of recombinant human CNTF into the adult rat neocortex. To study the astrocytes their cytosol wa s stained with antibodies against S100 beta and their nuclei were stai ned with propidium iodide (PI). Fluorescent images of astrocytic nucle i and somas were acquired using a confocal laser-scanning microscope a nd their areas were measured using the NIH image software. Within 24 h of treatment, CNTF induced a volume increase of the somas and nuclei of protoplasmic and fibrous astrocytes in vivo, and this effect persis ted for at least 48 h. To determine whether CNTF activates astrocytes directly, glial cultures were treated with CNTF (10 ng/ml) and were ev aluated by measuring the area of PI stained nuclei. CNTF stimulation i ncreased the size of both polygonal and process-bearing astroglia. Sin ce our studies in vivo have shown that CNTF induces other key aspects of gliosis (S. W. Levison et al., 1996; Exp. Neurol. 141, 256), we con clude that CNTF is a powerful activator of astrocytes and that it is l ikely responsible for the persistent glial hypertrophy observed follow ing injuries and diseases of the CNS. (C) 1998 Academic Press.