{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T10:08:11Z","timestamp":1784282891772,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Brain plasticity is often described as the capacity of the nervous system to change in response to development, experience, injury, disease, or treatment. That definition is useful, but it can obscure two clinically important points: plasticity is biologically constrained, and change is not always beneficial. This narrative review examines sex-dependent brain plasticity as a context-sensitive process rather than as a simple male\u2013female contrast. We distinguish four operational outcomes of plasticity: (i) reparative plasticity, which restores structure or function; (ii) compensatory plasticity, which preserves performance through alternative or more costly strategies; (iii) insufficient plasticity, in which reorganization is too weak or unstable to sustain function; and (iv) maladaptive plasticity, in which plastic change reinforces dysfunction, pain, excitability, rigidity, or decline. We also define adaptive reserve as the integrated capacity of neural, glial, vascular, immune, metabolic, endocrine, and gene-regulatory systems to support useful reorganization under stress. The review evaluates endocrine, synaptic, neuroimmune, mitochondrial, vascular, stress-related, and epigenetic mechanisms, indicating where evidence for sex-dependent effects is relatively strong and where it remains indirect, inconsistent, or context-dependent. Disease examples include autism spectrum disorder, attention-deficit\/hyperactivity disorder, epilepsy, intellectual disability, Alzheimer\u2019s disease, Parkinson\u2019s disease, amyotrophic lateral sclerosis, Huntington\u2019s disease, traumatic and ischemic injury, multiple sclerosis, chronic pain, aging, and systemic metabolic or inflammatory disorders. Throughout, biological sex is separated from gender-related social, diagnostic, and health-care determinants. We conclude that therapeutic strategies should not aim simply to enhance plasticity, but to guide it by matching intervention, timing, dose, biological readiness, and monitoring to the patient\u2019s adaptive state.<\/jats:p>","DOI":"10.3390\/biology15141176","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:00:52Z","timestamp":1784278852000},"page":"1176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-Dependent Brain Plasticity in Neurological Disease: From Biological Variability to Adaptive, Compensatory, and Maladaptive Trajectories"],"prefix":"10.3390","volume":"15","author":[{"given":"Alessandro","family":"Avitabile","sequence":"first","affiliation":[{"name":"Neurovisual Science Technology, Research Division (NEST-G.R.I.D.O.), 95125 Catania, Italy"},{"name":"Biomedicine, Neuroscience and Advance Diagnostics (BIND) Department, University of Palermo, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-2585","authenticated-orcid":false,"given":"Dario","family":"Rusciano","sequence":"additional","affiliation":[{"name":"Neurovisual Science Technology, Research Division (NEST-G.R.I.D.O.), 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Amato","sequence":"additional","affiliation":[{"name":"Neurovisual Science Technology, Research Division (NEST-G.R.I.D.O.), 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7556-6952","authenticated-orcid":false,"given":"Ludovica","family":"Cannizzaro","sequence":"additional","affiliation":[{"name":"Neurovisual Science Technology, Research Division (NEST-G.R.I.D.O.), 95125 Catania, Italy"},{"name":"Biomedicine, Neuroscience and Advance Diagnostics (BIND) Department, University of Palermo, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-0068","authenticated-orcid":false,"given":"Caterina","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Surgery, Kore University, 94100 Enna, Italy"},{"name":"Morgagni Ophthalmology Clinic, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/509282a","article-title":"Policy: NIH to balance sex in cell and animal studies","volume":"509","author":"Clayton","year":"2014","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"110003","DOI":"10.1016\/j.jneumeth.2023.110003","article-title":"Practical solutions for including sex as a biological variable (SABV) in preclinical neuropsychopharmacological research","volume":"401","author":"Dalla","year":"2024","journal-title":"J. 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