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Presently, little is known about the endogenous molecular mechanisms that regulate glial functions in the injured spinal cord. We previously reported that the expression of neuregulin\u20101 (Nrg\u20101) is acutely and chronically declined following traumatic SCI. Here, we investigated the potential ramifications of Nrg\u20101 dysregulation on glial and immune cell reactivity following SCI. Using complementary <jats:italic>in vitro<\/jats:italic> approaches and a clinically\u2010relevant model of severe compressive SCI in rats, we demonstrate that immediate delivery of Nrg\u20101 (500 ng\/day) after injury enhances a neuroprotective phenotype in inflammatory cells associated with increased interleukin\u201010 and arginase\u20101 expression. We also found a decrease in proinflammatory factors including IL\u20101\u03b2, TNF\u2010\u03b1, matrix metalloproteinases (MMP\u20102 and 9) and nitric oxide after injury. In addition, Nrg\u20101 modulates astrogliosis and scar formation by reducing inhibitory chondroitin sulfate proteoglycans after SCI. Mechanistically, Nrg\u20101 effects on activated glia are mediated through ErbB2 tyrosine phosphorylation in an ErbB2\/3 heterodimer complex. Furthermore, Nrg\u20101 exerts its effects through downregulation of MyD88, a downstream adaptor of Toll\u2010like receptors, and increased phosphorylation of Erk1\/2 and STAT3. Nrg\u20101 treatment with the therapeutic dosage of 1.5 \u03bcg\/day significantly improves tissue preservation and functional recovery following SCI. Our findings for the first time provide novel insights into the role and mechanisms of Nrg\u20101 in acute SCI and suggest a positive immunomodulatory role for Nrg\u20101 that can harness the beneficial properties of activated glia and inflammatory cells in recovery following SCI.<\/jats:p>","DOI":"10.1002\/glia.23150","type":"journal-article","created":{"date-parts":[[2017,4,29]],"date-time":"2017-04-29T18:38:36Z","timestamp":1493491116000},"page":"1152-1175","source":"Crossref","is-referenced-by-count":72,"title":["Neuregulin\u20101 positively modulates glial response and improves neurological recovery following traumatic spinal cord injury"],"prefix":"10.1002","volume":"65","author":[{"given":"Arsalan","family":"Alizadeh","sequence":"first","affiliation":[{"name":"Regenerative Medicine Program, Department of Physiology and Pathophysiology Spinal Cord Research Centre, University of Manitoba Winnipeg Manitoba R3E 0J9 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