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Targeting the underlying initiators and exacerbating factors could offer protective benefits. Among the proposed therapeutic agents, the steroid hormone progesterone (P4) has shown considerable potential. This study evaluates the protective effects of P4 (1.7 mg\/kg, administered subcutaneously once daily for a week) in a rat model of chronic cerebral hypoperfusion (CCH), provoked by the permanent bilateral ligation of the common carotid arteries. Redox and metabolic imbalances, specifically lipid and adenine nucleotide metabolism, were examined in serum and striatal crude synaptosomal fractions. Additionally, sensorimotor functions were assessed using non-invasive neurological tests. Biochemical analyses showed that P4 in CCH conditions contributed to the normalization of redox and metabolic homeostasis in both the serum and striatum. In the serum, this was accompanied by increased adenine nucleotide turnover, likely favoring protective adenosine signaling. In parallel, P4 alleviated the striatal oxidative burden while augmenting antioxidant response and promoting nucleotide catabolism. Our findings demonstrate that P4-mediated protection is accomplished through coordinated biochemical serum\u2013striatum responses, linking systemic and synaptic metabolic regulation with improved sensorimotor function and recovery from CCH-induced deficits.<\/jats:p>","DOI":"10.3390\/antiox15050610","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:39:34Z","timestamp":1779295174000},"page":"610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum and Striatal Redox and Metabolic Responses to Progesterone Treatment in Rats with Common Carotid Ligation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5307-2970","authenticated-orcid":false,"given":"Ivana Gu\u0161evac","family":"Stojanovi\u0107","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Endocrinology, VIN\u010cA Institute of Nuclear Sciences\u2013National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2074-1637","authenticated-orcid":false,"given":"Ana","family":"Todorovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Endocrinology, VIN\u010cA Institute of Nuclear Sciences\u2013National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4471-334X","authenticated-orcid":false,"given":"Filip","family":"Veljkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry, VIN\u010cA Institute of Nuclear Sciences\u2013National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9575-0960","authenticated-orcid":false,"given":"Katarina","family":"Bobi\u0107","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Endocrinology, VIN\u010cA Institute of Nuclear Sciences\u2013National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8641-1051","authenticated-orcid":false,"given":"Jelena","family":"Martinovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Endocrinology, VIN\u010cA Institute of Nuclear Sciences\u2013National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4573-2371","authenticated-orcid":false,"given":"Sne\u017eana","family":"Peji\u0107","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Endocrinology, VIN\u010cA Institute of Nuclear Sciences\u2013National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5605-6749","authenticated-orcid":false,"given":"Suzana","family":"Veli\u010dkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry, VIN\u010cA Institute of Nuclear Sciences\u2013National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5989-0031","authenticated-orcid":false,"given":"Zoran","family":"Stojanovi\u0107","sequence":"additional","affiliation":[{"name":"Group for Biomaterials and Biomedical Applications, Institute of Technical Sciences of SASA, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1448-9639","authenticated-orcid":false,"given":"Dunja","family":"Drakuli\u0107","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Endocrinology, VIN\u010cA Institute of Nuclear Sciences\u2013National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chen, X., Lu, L., Xiao, C., Lan, Y., Zhong, S., Qin, C., and Tang, Y. 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