Frontiers in Behavioral Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Фев. 6, 2025

Traumatic brain injury (TBI) affects more than 50 million people each year worldwide (Blaya et al., 2022) and leads to diverse functional impairments. Depending on the damaged regions, alterations may compromise different functions, which recover along time.Brain responses include events at molecular, cellular circuit levels (Zepeda 2004;Lim 2014;Kang 2022). However, study of plastic in humans a subcellular poses many difficulties. Therefore, loss recovery functions have been mainly assessed through behavioral evaluation, as well neuroimaging neurophysiological studies. When comparing animal models like rodents, we can only suggest potential contributions observed some but not all (Kozlowski 2013).Adding up complexity using experimental TBI proxy explore nervous humans, is difference outcomes male female clinical populations. Adult neurogenesis, has clearly demonstrated rats mice (for review, see Denoth-Lippuner Jessberger, 2021), beyond doubt (Sorrells 2018;Moreno-Jiménez 2019, for critical Oppenheim, 2019) explored mechanism subserving after damage, it our opinion that scientific community still far from reaching conclusion regarding its role repair.For purpose this opinion, would address four main questions: (1) Are there established sex-dependent differences outcome mirror humans? (2) To what extent possible extrapolate results obtained animals (3) Is neurogenesis adult rats? (4) non-debatable human brain?(1) From total pre-clinical research 2016 Pubmed, 7% studies females focus importance sex modeling (Späni 2018). Clinical trials observations are based populations under argument how hormonal fluctuations influence therefore results. Thus, hormones treated "problem" instead receiving proper attention unveil impact process recovery. occurs circumstances males compared females. In males, commonly produced several types contact collision or result military combat 2018); women falls, concussive impacts, intimate partner violence (St. Ivany Schminkey, 2016) presented together with multiorgan trauma (Biegon, 2021).Although sex-related damage matter debate, body work shows tend show better especially moderate-severe (Gupte 2019). This related increase hormone areas surrounding lesion review Stein, 2007). variations during estrous cycle also results: High progesterone time correlate females, while estrogens be detrimental 2007).While shown molecular including reduction excitotoxicity, antioxidant responses, synaptogenesis dendritic arborization 2001), context scarcely studied. Actually, knowledge one publication (Xiong 2007) addressed considering found constitutive number new neurons did differ between exposed TBI, cell proliferation (but neurogenesis) documented (Neale 2023). It worth mentioning documented, sexual dimorphisms response become evident pharmacological treatment other approaches aimed promoting 2007;Gómez-Porcuna 2024).The evidence ultimately factors subserve rats, positively long cycling appears. report worse 2019;Mikolic 2021) consider severity among variables, plays (Mikolic 2021). Thus extrapolating clinics accurate.(2) Animal capacity restore altered TBI. extrapolation lab needs evolution depends such age injury, location type always replicate models. Yet common resolve involving particular inflammation-involved mechanisms shared Liddelow 2024). Also, overcoming forms diaschisis (impairments remote communicated structure) recruitment regions initially involved performance provide means partial (Wiese 2004;Carrera Tononi, 2014;Boggs Among associated neuroplasticity rather alleviation upregulation neurotrophic signaling, modulation neurotransmitters, serotonin GABA (as previously discussed) (McGuire 2019;Shinoda 2021;Fox contrast, do yet support view constitutively born serve source recovery.(3) Neurogenesis species (Bonfanti Amrein, resident neural stem cells located two defined niches: subventricular zone lateral ventricles dentate gyrus hippocampus (Lois Alvarez-Buylla, 1993;Kuhn 1996) proliferate life give rise described steps (Kempermann 2004;Rasetto 2024).It strongly suggested these participate hippocampaldependent learning memory, spatial memory pattern separation (Miller Sahay, neurogenic positive negative conditions (i.e running vs inflammation) (van Praag 2002;Monje 2003;Perez-Dominguez 2019; Pérez-Domínguez 2017). although consistently reported (Arvidsson 2002;Aguilar-Arredondo Zepeda, 2018;Bielefeld 2024) newly-born integrate survive 2002;Kang their neurorepair remains unclear.The pioneering Arvidsson al. (2002), was first middle cerebral occlusion led increased zone. New acquired neuronal phenotype migrated towards striatum failed into circuit. Since then, works (Parent 2002;Yamashita 2006;Blaiss 2011;Sun 2015) evaluated endogenous induced cortical mostly affected similar even (Cuartero when generated bottle-neck effect prevents them significantly participating repair.Results hippocampal (which suffer TBI) since Nakatomi groups ours within functionally same structure (Aguilar-Arredondo 2018) does necessarily mean replenish area nor responsible reorganization. Yet, could reorganization focally circuit.During feedback inhibition granule increases physiological maturation (Groisman After newly hyperexcitable, potentially leading post-traumatic epilepsy due recurrent excitatory synapses sprouted mossy (Butler 2015;Neuberger Following sixfold, driven by just before parvalbumin + (PV) interneurons. Moreover, activation contribute hyperexcitability, suggesting young specifically enhance inputs onto PV interneurons (Kang Overall, prior around (just after) differentially excitation/inhibition balance shifts occur inconclusive.(4) brain, 1998 (Eriksson 1998). supported observation. Recent studies, colocalization markers refer presence Moreno-Jiménez claim interpretation data (see Alvarez-Buylla transcriptomic analyses revealed immature brains (Hochgerner 2018;Zhou detect (Cipriani 2018;Sorrells 2018;Franjic Transcriptomic meta-analysis sets mouse-based best comparison analyze given evolutionary primates humans. doublecortin cytoskeletal protein migrating neurons, used present non-neurogenic (Klempin 2011;Hagihara absence doublecortin, enough argue existence lack (Tosoni diversity concluded determined rodent markers, arguments against finding postmortem The re-analysis performed Tosoni (2023), yields possibility controversy arise methodological, conceptual biological confounders across studies.Interestingly, (Boldrini 2019;Tobin patients neurodegenerative diseases. considered an attempt compensation early triggered disease (Moreno-Jiménez supports showing population maintain "young phenotype" activate demand, meaning they post-mitotic plasticity complete local cues Palazzo 2018;Oppenheim, 2019;Jungenitz press).In article resumed findings Female outcomes. severe both outcomes, topic deserves close attention. Even rodents important look widen multiple processes accompany repair. Efforts being conducted stimulate promote reprogramming integration transplants understand repair.Plasticity traumatic widely lesser latter. often expected animals, equally case. pose questions approach limitations sex/gender focusing consequence are: sexdependent ( 2) nondebatable brain?

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