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. 2025 Jun 16:14:e68954.
doi: 10.2196/68954.

Effects of Selective Head-and-Neck Cooling on Brain Injury-Related Biomarker Levels and Symptom Rating Following a Boxing Bout: Protocol for an Exploratory Randomized Trial

Ali Al-Husseini  1 , Yelverton Tegner  2 , Kaj Blennow  3   4 , Henrik Zetterberg  3   4   5   6   7   8 , Niklas Marklund  9
Affiliations

Effects of Selective Head-and-Neck Cooling on Brain Injury-Related Biomarker Levels and Symptom Rating Following a Boxing Bout: Protocol for an Exploratory Randomized Trial

Ali Al-Husseini et al. JMIR Res Protoc. .

Abstract

Background: Head impacts are common in contact sports such as boxing and occur at times of elevated core body and brain temperatures induced by the exercise. Following impact, elevated brain temperature may lead to the development of exacerbated brain injury that can be monitored by blood biomarkers. Blood-brain biomarkers S100B and glial fibrillary acidic protein (GFAP) reflect glial injury; neurofilament light (NFL), axonal injury; and Neuron-Specific Enolase (NSE) and Tubulin-associated unit (tau), neuronal injury. Time to peak levels post injury for these biomarkers varies. Levels of S100B l peak early post injury, while NSE, GFAP, and tau are regarded as subacute markers, and NFL shows prolonged increases. We attempt to cover a large spectrum of first week postfight alterations in blood-brain biomarkers and their response to head-neck cooling.

Objective: We hypothesized that acute head-and-neck cooling, recently shown to shorten return-to-play in concussed ice hockey players, applied acutely following a boxing bout, is associated with an attenuated concentration of blood biomarkers and improved symptom rating.

Methods: The trial is academically driven and funded by external and hospital research funds. Young, healthy elite boxers aged ≥18 years are recruited. Before, and immediately after a competitive boxing bout consisting of 2 or 3 rounds of 2 minutes each, blood samples are drawn. Boxers are randomized to intervention or control management by 1:1 allocation before baseline testing. After the initial postfight blood sample is drawn and symptom rating using the Sports Concussion Assessment Tool-5 (SCAT-5) has been collected, the boxers receive either acute selective head-and-neck cooling for 45 minutes or routine postfight management. The number of head impacts is counted in all boxers on match video recordings. In both groups, blood samples are drawn 45 minutes after the initial postbout blood sample, as well as 3 and 6 days post fight. At all blood sampling time points, the number of symptoms (NOS) and symptom severity score (SSS) are assessed using the symptom rating part of the SCAT-5. The primary endpoint is the difference in biomarker levels (GFAP, NFL, tau, UCH-L1, neuronal-specific enolase) immediately post fight and preintervention, to those obtained at 6 days post fight. The postfight SCAT-5 NOS and SSS are secondary endpoints.

Results: Recruitment started in November 2021 and is ongoing. So far, 41 boxers have been included: 20 controls and 21 cooled. Data collection started in October 2024 following the completion of blood sample analysis. We expect to recruit more boxers before the middle of 2025, but challenges with recruitment may limit this.

Conclusions: There is no treatment available for boxing-induced brain injury. Biomarkers are surrogate yet objective markers of brain injury, and the head-and-neck cooling treatment may attenuate the concentration of brain injury-related biomarkers as well as reduce symptoms induced by head impacts attained during a boxing fight.

Trial registration: ClinicalTrials.gov NCT06386484; https://clinicaltrials.gov/study/NCT06386484.

International registered report identifier (irrid): DERR1-10.2196/68954.

Keywords: biomarker; boxing; glial fibrillary acidic protein; neurofilament-light; sports concussion.

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Conflict of interest statement

Conflicts of Interest: YT is a scientific advisor for PolarCool Inc. Lund, Sweden. NM previously was a scientific advisor for PolarCool Inc. Lund, Sweden. Polar Cool provides the cooling helmet, although has not influenced the design of the study protocol. HZ has served at scientific advisory boards and as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KB has served as a consultant, on advisory boards, or data monitoring committees for Abcam, Axon, Biogen, and JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Prothena, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. IR has served on advisory boards and given talks sponsored by Biogen, Bayer, Merck, Roche, GlaxoSmithKline, TEVA, Sanofi, and UCB.

Figures

Figure 1
Figure 1
Boxers that participate in direct final bouts or single-fight events will only engage in one boxing bout. SCAT-5: Sports Concussion Assessment Tool-5.
Figure 2
Figure 2
Boxers who participate in tournaments can either fight one or two boxing bouts, depends on whether they win or lose. SCAT-5: Sports Concussion Assessment Tool-5.
Figure 3
Figure 3
(A) The PolarCap unit is a powerful mobile cooling system. (B) The Polar Coolant is transported through the silicone head cap. (C) To insulate against the cold, a neoprene cover is applied on top of the cap.
Figure 4
Figure 4
All allocation and randomization occur after signed informed consent and before baseline testing.
See this image and copyright information in PMC

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