{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:06:02Z","timestamp":1787018762425,"version":"build-2736575974"},"reference-count":59,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2016,7,20]],"date-time":"2016-07-20T00:00:00Z","timestamp":1468972800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:p>Neuroinflammation subsequent to developmental brain injury contributes to a wave of secondary neurodegeneration and to reactive astrogliosis that can inhibit oligodendrocyte progenitor differentiation and subsequent myelination. Here we evaluated the therapeutic efficacy of a small molecule antagonist for a TGF\u00df receptor in a model of moderate perinatal hypoxia-ischemia (H-I). Osmotic pumps containing SB505124, an antagonist of the type 1 TGF\u00df1 receptor ALK5, or vehicle, were implanted three days after H-I induced at postnatal day 6. Perinatal H-I induced selective neuronal death, ventriculomegaly, elevated CNS levels of IL-6 and IL-1\u03b1, astrogliosis, and fewer proliferating oligodendrocyte progenitors. Myelination was reduced by \u223c50%. Anterograde tracing revealed extensive axonal loss in the corticospinal tract. These alterations correlated with functional impairments across a battery of behavioral tests. All of these parameters were brought back towards normal levels with SB505124 treatment. Notably, SB505124 preserved neurons in the hippocampus and thalamus. Our results indicate that inhibiting ALK5 signaling, even as late as three days after injury, creates an environment that is more permissive for oligodendrocyte maturation and myelination producing significant improvements in neurological outcome. This new therapeutic would be especially appropriate for moderately preterm asphyxiated infants, for whom there is presently no FDA approved neuroprotective therapeutic.<\/jats:p>","DOI":"10.1177\/0271678x16638669","type":"journal-article","created":{"date-parts":[[2016,3,16]],"date-time":"2016-03-16T22:14:17Z","timestamp":1458166457000},"page":"787-800","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["Delayed ALK5 inhibition improves functional recovery in neonatal brain injury"],"prefix":"10.1177","volume":"37","author":[{"given":"Mariano","family":"Guardia Clausi","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Physiology and Neuroscience Rutgers-New Jersey Medical School, Newark, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W","family":"Levison","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology and 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