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In this context, we investigated the effects of varying frequencies of recurrent concussions on exploratory behavior, hippocampal mitochondrial bioenergetics, and nitrosative stress in adolescent male Swiss mice (32 days old) subjected to a weight-drop model over 10 days and allocated to Control, 4, 7, and 10-concussion groups. Exploratory behavior was assessed using the open field test 24\u00a0h post-injury, while hippocampal mitochondrial respiration (high-resolution respirometry) and nitrosative stress markers (3-nitrotyrosine and iNOS) were evaluated 6 days after the final injury. Twenty-four hours after the final injury, behavioral hyperactivity peaked following 7 concussions. While this phenotype was attenuated after 10 recurrent concussions, exploratory alterations (increased proportion of mobile time, greater time spent in the center, and fewer immobile episodes) persisted relative to controls. Respirometry at 6 days post-injury indicated a threshold effect for mitochondrial dysfunction: although 7 concussions compromised maximal electron transfer capacity, basal and phosphorylation states were impaired only after 10 concussions, resulting in a reduction in ATP synthase activity. The severe bioenergetic failure coincided with increased hippocampal protein nitrosylation (3-NT), indicating a progressive metabolic deterioration subsequent to the early behavioral hyperactivity. Our findings suggest that early hyperactivity precedes bioenergetic failure, reflecting the sequential progression of the injury. Thus, this transient behavioral phenotype may serve as a predictive marker for subsequent mitochondrial collapse.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>\n                  <jats:p>Dose-dependent neurometabolic and behavioral progression following recurrent concussions in the hippocampus of young mice. The diagram illustrates the sequential relationship between the acute behavioral phenotype observed 24\u00a0h post-injury and the subacute mitochondrial dysfunction evaluated 6 days post-injury. Initially, exposure to 4 concussions induces early exploratory alterations, characterized by an increased proportion of mobility time in the open field, but without significant impairments in the respiratory chain complexes, indicating an early mitigation of metabolic stress. Subsequently, 7 concussions trigger a peak in motor hyperactivity, evidenced by a significant increase in line crossings. This behavioral peak precedes the onset of mitochondrial stress, which is marked by a compromised maximal electron transfer capacity (ETS) and early Complex I inhibition. Finally, the cumulative damage of 10 concussions leads to an attenuation of the hyperactive locomotor phenotype, suggesting a threshold effect. Concurrently, this stage is characterized by a severe bioenergetic collapse featuring the sustained inhibition of NADH dehydrogenase (Complex I) and a drastic reduction in ATP synthase activity. This severe metabolic failure directly coincides with elevated hippocampal nitrosative stress, demonstrated by the significant accumulation of 3-nitrotyrosine (3-NT). Collectively, these findings raise the possibility that acute hyperactivity could serve as an early behavioral correlate to the later development of mitochondrial exhaustion and nitrosative damage.<\/jats:p>","DOI":"10.1007\/s11010-026-05780-y","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:54:40Z","timestamp":1792659280000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Behavioral hyperactivity and hippocampal mitochondrial dysfunction following recurrent concussions in young mice"],"prefix":"10.1007","author":[{"given":"Leandro Machado Severo","family":"Feiteiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas Buchmann","family":"Godinho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Felipe","family":"Alchieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Sanguinet","family":"Sanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane Duarte","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele Rechia","family":"Fighera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e9lix Alexandre","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Flavia","family":"Furian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro Schneider","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4045-4827","authenticated-orcid":false,"given":"Luiz Fernando Freire","family":"Royes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"5780_CR1","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1016\/S1474-4422(22)00309-X","volume":"21","author":"AIR Maas","year":"2022","unstructured":"Maas AIR, Menon DK, Manley GT et al (2022) Traumatic brain injury: progress and challenges in prevention, clinical care, and research. 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