{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T07:20:48Z","timestamp":1780730448323,"version":"3.54.1"},"reference-count":192,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"crossref","award":["#25-75-10137"],"award-info":[{"award-number":["#25-75-10137"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hydrogen sulfide (H2S) is a gasotransmitter that plays a crucial role in regulating pathological processes following injury to the central and peripheral nervous systems. This review systematizes current data on various classes of H2S donors and inhibitors of its biosynthesis in neurotrauma and related experimental models. Inorganic donors (e.g., NaHS, Na2S, and STS) rapidly suppress oxidative stress and inflammation, supporting the recovery of synaptic plasticity and cognitive function. Organic donors (e.g., GYY4137, ACS67, ACS84, SPRC, ADT-OH and its derivatives, S-memantine, and MTC) provide sustained H2S release, stabilize the blood\u2013brain barrier, and exhibit antiapoptotic activity. Natural donors (e.g., DADS, DATS, and SAMe) demonstrate high biocompatibility, inhibit pyroptosis, and enhance antioxidant defense mechanisms. Hybrid systems\u2014including nanoparticles and hydrogels\u2014enable targeted delivery and prolonged action, thereby stimulating regeneration and angiogenesis. Thiol-activated donors (e.g., COS\/H2S and AlaCOS) allow controlled H2S release, offering broad opportunities for precise modulation of its concentration within target tissues. Inhibitors (e.g., AOAA, PAG, oxamic hydrazide 1, L-aspartic acid, benserazide, and NSC4056) of H2S biosynthesis underscore the physiological importance of this gasotransmitter, as their administration enhances neuroinflammation and diminishes neuroprotection. The analysis reveals a general pattern: all classes of H2S donors effectively modulate key pathological mechanisms, differing in their rate, duration, and specificity of action. These findings highlight the therapeutic promise of H2S-based pharmacological agents in clinical neurotraumatology, while emphasizing the need for further research to optimize delivery systems, enhance efficacy, and minimize adverse effects.<\/jats:p>","DOI":"10.3390\/ijms262411842","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:52:24Z","timestamp":1765205544000},"page":"11842","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inorganic, Synthetic, Natural, and Innovative Hybrid Hydrogen Sulfide Donors and Inhibitors of Its Biosynthesis in the Treatment of Central and Peripheral Nervous System Injuries: A Systematic Analytical Review"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4036-5410","authenticated-orcid":false,"given":"Stanislav","family":"Rodkin","sequence":"first","affiliation":[{"name":"Research Laboratory \u201cMedical Digital Images Based on the Basic Model\u201d, Department of Bioengineering, Institute of Living Systems, Don State Technical University, 344000 Rostov-on-Don, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1929-6345","authenticated-orcid":false,"given":"Sergey","family":"Golovin","sequence":"additional","affiliation":[{"name":"Research Laboratory \u201cMedical Digital Images Based on the Basic Model\u201d, Department of Bioengineering, Institute of Living Systems, Don State Technical University, 344000 Rostov-on-Don, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4349-5897","authenticated-orcid":false,"given":"Stanislav","family":"Bachurin","sequence":"additional","affiliation":[{"name":"Research Laboratory \u201cMedical Digital Images Based on the Basic Model\u201d, Department of Bioengineering, Institute of Living Systems, Don State Technical University, 344000 Rostov-on-Don, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7788-288X","authenticated-orcid":false,"given":"Anton","family":"Lisovin","sequence":"additional","affiliation":[{"name":"Research Laboratory \u201cMedical Digital Images Based on the Basic Model\u201d, Department of Bioengineering, Institute of Living Systems, Don State Technical University, 344000 Rostov-on-Don, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8335-1380","authenticated-orcid":false,"given":"Inna","family":"Vasilieva","sequence":"additional","affiliation":[{"name":"N.V. 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Zalessky, Novosibirsk State Medical University, Krasny Prospekt, 52, Department of Medical Rehabilitation, Novosibirsk Regional Clinical Hospital of War Veterans No. 3, Demyan the Poor, 71, 630005 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0952-6856","authenticated-orcid":false,"given":"Vasilii","family":"Chulkov","sequence":"additional","affiliation":[{"name":"Department of Hospital Therapy, Yaroslav-the-Wise Novgorod State University, Derzhavina St. 6, 173020 Veliky Novgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5856-0404","authenticated-orcid":false,"given":"Mitkhat","family":"Gasanov","sequence":"additional","affiliation":[{"name":"Department of Hospital Therapy, Yaroslav-the-Wise Novgorod State University, Derzhavina St. 6, 173020 Veliky Novgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e075049","DOI":"10.1136\/bmjopen-2023-075049","article-title":"Global, Regional and National Burden of Traumatic Brain Injury and Spinal Cord Injury, 1990\u20132019: A Systematic Analysis for the Global Burden of Disease Study 2019","volume":"13","author":"Guan","year":"2023","journal-title":"BMJ Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/S1474-4422(22)00309-X","article-title":"Traumatic Brain Injury: Progress and Challenges in Prevention, Clinical Care, and Research","volume":"21","author":"Maas","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1097\/SAP.0000000000003480","article-title":"Mechanisms and Treatments of Peripheral Nerve Injury","volume":"91","author":"Liu","year":"2023","journal-title":"Ann. 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