Ciliary neurotrophic factor (CNTF) promotes survival and enhances long-distance regeneration of injured axons in parts of the\nadult CNS. Here we tested whether CNTF gene therapy targeting corticospinal neurons (CSN) in motor-related regions of the\ncerebral cortex promotes plasticity and regrowth of axons projecting into the female adult F344 rat spinal cord after moderate\nthoracic (T10) contusion injury (SCI). Cortical neurons were transduced with a bicistronic adeno-associated viral vector (AAV1)\nexpressing a secretory form of CNTF coupled to mCHERRY (AAV-CNTFmCherry) or with control AAV only (AAV-GFP) two\nweeks prior to SCI. In some animals, viable or nonviable F344 rat mesenchymal precursor cells (rMPCs) were injected into the\nlesion site two weeks after SCI to modulate the inhibitory environment. Treatment with AAV-CNTFmCherry, as well as with\nAAV-CNTFmCherry combined with rMPCs, yielded functional improvements over AAV-GFP alone, as assessed by open-field\nand Ladderwalk analyses. Cyst size was significantly reduced in the AAV-CNTFmCherry plus viable rMPC treatment group.\nCortical injections of biotinylated dextran amine (BDA) revealed more BDA-stained axons rostral and alongside cysts in the\nAAV-CNTFmCherry versus AAV-GFP groups. After AAV-CNTFmCherry treatments, many sprouting mCherry-immunopositive\naxons were seen rostral to the SCI, and axons were also occasionally found caudal to the injury site. These data suggest that\nCNTF has the potential to enhance corticospinal repair by transducing parent CNS populations.
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