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Growth hormone (GH) expression is upregulated in several brain areas when exposed to HI conditions, suggesting actions as a local neurotrophic factor. It is known that GH, either exogenous and\/or locally expressed, exerts neuroprotective and regenerative actions in cerebellar neurons in response to HI. However, it is still controversial whether GH can cross the blood\u2013brain barrier (BBB), and if its effects are exerted directly or if they are mediated by other neurotrophic factors. Here, we found that in ovo microinjection of Cy3-labeled chicken GH resulted in a wide distribution of fluorescence within several brain areas in the chicken embryo (choroid plexus, cortex, hypothalamus, periventricular areas, hippocampus, and cerebellum) in both normoxic and hypoxic conditions. In the cerebellum, Cy3-GH and GH receptor (GHR) co-localized in the granular and Purkinje layers and in deep cerebellar nuclei under hypoxic conditions, suggesting direct actions. Histological analysis showed that hypoxia provoked a significant modification in the size and organization of cerebellar layers; however, GH administration restored the width of external granular layer (EGL) and molecular layer (ML) and improved the Purkinje and granular neurons survival. Additionally, GH treatment provoked a significant reduction in apoptosis and lipoperoxidation; decreased the mRNA expression of the inflammatory mediators (TNF\u03b1, IL-6, IL-1\u03b2, and iNOS); and upregulated the expression of several neurotrophic factors (IGF-1, VEGF, and BDNF). Interestingly, we also found an upregulation of cerebellar GH and GHR mRNA expression, which suggests the existence of an endogenous protective mechanism in response to hypoxia. Overall, the results demonstrate that, in the chicken embryo exposed to hypoxia, GH crosses the BBB and reaches the cerebellum, where it exerts antiapoptotic, antioxidative, anti-inflammatory, neuroprotective, and neuroregenerative actions.<\/jats:p>","DOI":"10.3390\/ijms231911546","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T23:09:29Z","timestamp":1664492969000},"page":"11546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Growth Hormone (GH) Crosses the Blood\u2013Brain Barrier (BBB) and Induces Neuroprotective Effects in the Embryonic Chicken Cerebellum after a Hypoxic Injury"],"prefix":"10.3390","volume":"23","author":[{"given":"Rosario","family":"Baltazar-Lara","sequence":"first","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Campus Juriquilla, Universidad Nacional Aut\u00f3noma de Mexico, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janeth Mora","family":"Zenil","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Campus Juriquilla, Universidad Nacional Aut\u00f3noma de Mexico, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Carranza","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Campus Juriquilla, Universidad Nacional Aut\u00f3noma de Mexico, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"\u00c1vila-Mendoza","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Campus Juriquilla, Universidad Nacional Aut\u00f3noma de Mexico, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos G.","family":"Mart\u00ednez-Moreno","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Campus Juriquilla, Universidad Nacional Aut\u00f3noma de Mexico, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6235-8695","authenticated-orcid":false,"given":"Carlos","family":"Ar\u00e1mburo","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Campus Juriquilla, Universidad Nacional Aut\u00f3noma de Mexico, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1409-500X","authenticated-orcid":false,"given":"Maricela","family":"Luna","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Campus Juriquilla, Universidad Nacional Aut\u00f3noma de Mexico, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.clp.2016.04.002","article-title":"Pathophysiology of Birth Asphyxia","volume":"43","author":"Rainaldi","year":"2016","journal-title":"Clin. 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