Concussion is increasingly recognized not simply as a transient clinical event but as a complex biological process in which the apparent resolution of symptoms may not necessarily coincide with complete recovery of the brain. That distinction, long debated in sports medicine and neurotrauma research, sits at the center of a new Research Topic published in Frontiers in Neurology under the title Multiple Concussions: From Preclinic to Clinic. The collection, introduced by an editorial from Giuseppe Lazzarino of LTA-Biotech in Italy, Stefano Signoretti of UniCamillus and Sant’Eugenio Hospital in Rome, and Valentina Di Pietro of the University of Birmingham, gathers pre-clinical, clinical and translational perspectives on one of the most challenging questions in concussion research: when does repeated exposure cease to be transient and begin to produce persistent brain dysfunction?
The editorial argues that a key challenge in concussion management remains the absence of a readily accessible measure of biological recovery. Clinical assessment continues to rely heavily on symptoms, neurological examination and neurocognitive function, yet these measures may normalize while molecular, metabolic and cellular alterations persist. This creates a potential mismatch between the clinical recovery of the individual and the biological recovery of the brain. The problem becomes particularly acute, the authors note, when decisions about return-to-play, return-to-learn or return to other activities are made in the context of continued exposure to head impacts, a point they tie to contributions by Bevilacqua and colleagues within the collection.
A first major theme of the Research Topic is the search for objective biomarkers of concussion and recovery. Molecular biomarkers, the editorial explains, have the potential to provide information that cannot be obtained from symptoms alone, particularly if they can distinguish acute injury from persistent or cumulative effects. The studies included in the collection contribute to the growing effort to identify molecular signatures associated with repeated concussion and to determine whether these signatures correlate with clinical symptoms, cognitive performance and recovery trajectories, work represented by Le Belle and colleagues. Importantly, the editors stress that future biomarkers will need to demonstrate not only diagnostic value but also the ability to inform prognosis and, ultimately, individualized clinical decision-making, a requirement highlighted in the contribution by Napora and colleagues.
A second major theme concerns sub-concussive exposure. The absence of a clinically recognized concussion does not necessarily imply the absence of biological consequences. Athletes in contact and collision sports may experience numerous head impacts over a season or across an entire sporting career without reporting symptoms. Determining whether the cumulative burden of these exposures produces measurable and clinically meaningful alterations remains a critical research priority. According to the editorial, contributions examining sub-concussive exposure challenge the traditional binary distinction between concussion and no concussion and highlight the need to consider head-impact exposure as a continuum rather than a yes-or-no diagnosis.
Pre-clinical models provide another essential component of that continuum. Repeated-injury paradigms allow researchers to investigate questions that are difficult to address clinically, including the relationship between the number, interval and severity of impacts and subsequent pathological outcomes. Among the important unanswered questions the editors identify is whether there is a threshold, or perhaps a more complex interaction between injury burden, timing and individual susceptibility, beyond which the brain fails to return to its previous state. Rather than searching for a universal number of concussions that is too many, they argue, future research may need to identify the biological conditions under which repeated injury becomes increasingly harmful.
These models are also essential for understanding the mechanisms linking repetitive head trauma with persistent neuroinflammation, metabolic dysfunction, axonal and synaptic abnormalities, and neurodegenerative processes. In particular, the relationship between repetitive traumatic brain injury and chronic traumatic encephalopathy, or CTE, remains an area of considerable scientific interest and debate. The editorial is careful to caution that the presence of repetitive head impacts alone should not be assumed to predict an inevitable neurodegenerative outcome. Understanding why some individuals appear resilient whereas others develop persistent neurological or neuropsychiatric consequences, the authors write, will require integration of injury characteristics with biological, genetic, environmental and lifestyle factors.
The clinical implications of these questions are substantial. Current approaches to return-to-play and return-to-learn increasingly recognize that recovery should be individualized, progressive and multidimensional. Nevertheless, clinicians still lack robust tools capable of determining whether an apparently recovered brain remains biologically vulnerable. Contributions addressing clinical management and educational reintegration, the editorial suggests, provide an important bridge between mechanistic research and the realities faced by athletes, students, families, clinicians and sporting organizations, groups who must make consequential decisions about activity resumption with incomplete information about the state of the underlying biology.
Taken together, the articles in the Research Topic reinforce the need to move beyond a simple symptom-based model of concussion. The future of concussion research, the editors contend, will require integration rather than isolation, a point emphasized in the contribution by Napora and colleagues: molecular biomarkers must be integrated with clinical assessment, experimental models with longitudinal human studies, individual concussions with cumulative exposure, and acute recovery with long-term outcomes. No single line of evidence, on its own, is likely to resolve the question of when repeated head impacts tip the brain from transient disruption into persistent dysfunction.
Perhaps most provocatively, the editorial suggests that the question of how many concussions are too many may ultimately prove to be the wrong question. The more clinically relevant question, the authors propose, drawing on the contribution by Remigio-Baker and colleagues, may be how many are too many for this individual, at this particular stage of recovery. Answering that question, they argue, will require sensitive measures of biological vulnerability, better characterization of cumulative exposure and a stronger understanding of the mechanisms that determine whether an individual recovers or progresses after repeated head impacts.
The editorial, published on 29 October 2026 in Frontiers in Neurology as part of the journal’s Neurotrauma section, frames Multiple Concussions: From Pre-clinic to Clinic as a contribution to an ongoing effort spanning the translational spectrum. The ultimate goal, the editors conclude, is not simply to identify the consequences of repeated head impacts but to develop the knowledge and tools necessary to recognize vulnerability, guide safer recovery and prevent potentially avoidable long-term consequences. Until such tools exist, the collection underscores, the gap between how a concussed individual feels and what is happening biologically in their brain remains one of the field’s most pressing unsolved problems.
Subject of Research: An editorial introducing a Research Topic on the biological effects of multiple concussions and sub-concussive head impacts, spanning biomarkers, pre-clinical models and clinical recovery.
Article Title: Editorial: Multiple concussions: from preclinic to clinic
Article References: Lazzarino, G., Signoretti, S., & Di Pietro, V. (2026). Editorial: Multiple concussions: from preclinic to clinic. Frontiers in Neurology, 17, Article 2001679. https://doi.org/10.3389/fneur.2026.2001679
Image Credits: AI Generated
DOI: 10.3389/fneur.2026.2001679
Keywords: concussion, repeated head impacts, sub-concussive exposure, biomarkers, neuroinflammation, chronic traumatic encephalopathy, return-to-play, neurotrauma, brain recovery, sports-related concussion, pre-clinical models, Editorial
News Source: Ophelia Keating. (October 29, 2026). When Do Repeated Concussions Stop Being Transient? New Research Topic Weighs In. Scienmag.
