Open research questions in Traumatic Brain Injury and Neurovascular Disturbances

What the literature leaves open

• Limited effective interventions to prevent TBI-associated ARDS. The need for a randomized, controlled trial to evaluate the effect of early intravenous magnesium sulfate on clinical outcomes in patients with moderate-to-severe TBI. The lack of a standardized approach to managing patients with moderate-to-severe TBI and ARDS.

  Effect of early intravenous magnesium sulfate on clinical outcomes in patients with moderate to severe traumatic brain injury: a study protocol for a randomized controlled trial · 2026 · DOI

• subjective evaluation method, - absence of blinded assessment, - limited sample size, - no comparative analysis with conventional fixation methods, - limited follow-up for one patient

  Experience with PEEK Clamp Fixation of Custom Porous Hydroxyapatite Implants in Cranioplasty: A Preliminary Single-Center Feasibility Case Series · 2026 · DOI

• comparative analysis with conventional fixation methods, - long-term evaluation of osseointegration, - assessment of cosmetic outcomes using objective measures, - evaluation of the technique in a larger patient population

  Experience with PEEK Clamp Fixation of Custom Porous Hydroxyapatite Implants in Cranioplasty: A Preliminary Single-Center Feasibility Case Series · 2026 · DOI

• The efficacy and safety of oxiracetam for cognitive and functional outcomes after acute TBI in Chinese populations are uncertain. There is a need for a systematic review and meta-analysis to evaluate the efficacy and safety of oxiracetam.

  Efficacy and safety of oxiracetam for cognitive and functional outcomes after acute traumatic brain injury in Chinese populations: a systematic review and meta-analysis of randomized controlled trials · 2026 · DOI

• rationale in for provides these the Most randomized evidence on oxiracetam after TBI comes from small trials conducted in China. These trials address three distinct questions: whether oxiracetam adds benefit to usual care, whether it is more effective than piracetam, and whether it adds benefit to a nimodipine-based regimen. Comparability is further limited by differences in formulation, route, dose, treatment duration, time from injury to treatment, outcome assessment, injury severity, and background care. Consequently, estimates from short-course intravenous racemic oxiracetam, oral regimens, and 90-day evaluations of L-oxiracetam may not reflect the same clinical effect. Accordingly, we systematically reviewed randomized trials conducted in China that evaluated oxiracetam in adults with acute TBI. We estimated efficacy and safety separately by comparator and outcome domain, verified treatment regimens and numerical data against the source reports, and summarized the contemporary phase 3 LOCATE trial narratively because its intervention and follow-up differed from those of the earlier trials.

  Efficacy and safety of oxiracetam for cognitive and functional outcomes after acute traumatic brain injury in Chinese populations: a systematic review and meta-analysis of randomized controlled trials · 2026 · DOI

• There is a need to assess the latest burden of TBI and analyze differences in terms of country, age, sex, and cause. There is a lack of understanding of the trend of injury causes in different age groups and regions from 1990 to 2021.

  Global, regional, and national burdens of traumatic brain injury from 1990 to 2021 · 2025 · DOI

• Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of cellular antioxidant defense, but its role in maintaining neurovascular integrity after TBI remains unclear.

  Nrf2 regulates ICAM-1-mediated neutrophil extracellular trap formation after traumatic brain injury. · 2026 · DOI

• Background: Cerebral autoregulation stabilizes cerebral blood flow over a range of cerebral perfusion pressures, but the precise shape of the pressure-flow relationship remains debated.

  The Role of Smooth Muscle Cell Heterogeneity in Cerebral Autoregulation: A Multi-Scale Physics-Based Modeling Study · 2026 · DOI

• Further studies investigating the mechanisms by which antisecretory factor act are warranted.

  Salovum® reduces mortality in isolated severe traumatic brain injury: a randomized phase II trial · 2026 · DOI

• The impact of temporal and individual differences in respiratory and cerebrovascular responses on the assessment of cerebrovascular carbon dioxide (CO 2 ) reactivity (CVR) using the Douglas bag method remains unclear.

  Hidden Overshoot in Cerebral Blood Flow: Implications for Accurate Assessment of Cerebral CO 2 Reactivity · 2026 · DOI

• BACKGROUND AND OBJECTIVES: The optimal blood pressure (BP) target after endovascular thrombectomy (EVT) remains elusive.

  Autoregulation-Guided Blood Pressure Targets After Stroke Thrombectomy · 2026 · DOI

• Conclusion Care varies widely and is influenced by donor status and institutional culture, underscoring the need for clearer guidance and provider support.

  Management of non-survivable head trauma: Opportunities for improvement · 2026 · DOI

• Traumatic brain injury (TBI) remains a leading cause of chronic neurological impairment, yet the cellular mechanisms underlying long-term neurodegeneration in TBI remain incompletely understood.

  Astrocyte activation persists one year after TBI: a dynamic shift from inflammation to neurodegeneration · 2025 · DOI

• Importance: While national guidelines recommend avoidance of hypoxia, hypotension, and hypocarbia in the prehospital care of traumatic brain injury (TBI), limited data validate the association of these adverse physiologic events with TBI outcomes.

  Adverse Prehospital Events and Outcomes After Traumatic Brain Injury · 2025 · DOI

• The reasons remain unclear, with the low level of evidence in the field of ICP monitoring and the recency of changes in guideline recommendations as potential contributors.

  Current practice of intracranial pressure monitoring in children with severe traumatic brain injury—a nationwide prospective surveillance study in Germany · 2024 · DOI

• Mean arterial pressure (MAP) plays a crucial role in cerebral perfusion pressure, but its relationship with mortality in SAE patients remains unclear.

  Optimal target mean arterial pressure for patients with sepsis-associated encephalopathy: a retrospective cohort study · 2024 · DOI

• Importance: The optimal timing for fixation of extremity fractures after traumatic brain injury (TBI) remains controversial.

  Early vs Late Fixation of Extremity Fractures Among Adults With Traumatic Brain Injury · 2024 · DOI

• Prospective and real-world validation studies reveal a critical evidence gap. While AI tools improve diagnostic metrics and workflow efficiency, robust randomized controlled trials demonstrating direct improvement in patient-centered outcomes are still lacking.

  Artificial intelligence for traumatic brain injury imaging: a translational review from algorithm development to clinical implementation · 2026 · DOI

• Successful translation of AI tools requires sustained, synergistic collaboration across disciplines—uniting data scientists, radiologists, neurosurgeons, intensivists, and emergency physicians—to address core translational challenges.

  Artificial intelligence for traumatic brain injury imaging: a translational review from algorithm development to clinical implementation · 2026 · DOI

• Future studies should investigate the clinical implications of the study's findings. Future studies should explore the use of other approaches to assess the significance of K2 in SAVR population. Future studies should examine the effects of other factors on cerebral autoregulation in SAVR population.

  Accounting for squared coherence marginally improves the discriminative power of frequency domain cerebral autoregulation markers in surgical aortic valve replacement patients · 2026 · DOI

• The study identifies a gap in the current understanding of the practical relevance of accounting for the significance of K2 in SAVR population. The study identifies a need for a new approach to assess the significance of K2 in SAVR population.

  Accounting for squared coherence marginally improves the discriminative power of frequency domain cerebral autoregulation markers in surgical aortic valve replacement patients · 2026 · DOI

• Integration of TCD with other emerging monitoring technologies, such as cerebrospinal fluid and serum biomarkers. Development of robotic TCD and AI-assisted analysis.

  Transcranial Doppler ultrasonography in geriatric anesthesia: moving toward personalized brain protection strategies · 2026 · DOI

• Conventional anesthetic management often overlooks age-related vulnerabilities. The pathophysiology of perioperative neurological complications is complex and involves multifactorial interactions.

  Transcranial Doppler ultrasonography in geriatric anesthesia: moving toward personalized brain protection strategies · 2026 · DOI

• The increasing rate of micromobility-related injuries poses a significant challenge to trauma care systems. The lack of detailed clinical and neurosurgical outcome data hinders the development of effective prevention strategies. The need for targeted interventions to reduce micromobility-related injuries is a significant challenge.

  The Fast and the Fragile: Neurosurgical Trauma in the Age of Micromobility · 2026 · DOI

• The study is limited to a single Level-1 trauma center, which may not be representative of all trauma centers. The study relies on retrospective data, which may be subject to biases and limitations. The study does not provide a direct comparison to other modes of transportation.

  The Fast and the Fragile: Neurosurgical Trauma in the Age of Micromobility · 2026 · DOI

Most-cited papers in Traumatic Brain Injury and Neurovascular Disturbances

• ASSESSMENT OF OUTCOME AFTER SEVERE BRAIN DAMAGE A Practical Scale · The Lancet · 1975 · 5,710 citations
• Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study · The Lancet · 2009 · 1,404 citations
• The Canadian CT Head Rule for patients with minor head injury · The Lancet · 2001 · 1,260 citations
• Blood GFAP as an emerging biomarker in brain and spinal cord disorders · Nature Reviews Neurology · 2022 · 740 citations
• Traumatic Brain Injury in Older Adults: Epidemiology, Outcomes, and Future Implications · Journal of the American Geriatrics Society · 2006 · 540 citations
• ProTECT: A Randomized Clinical Trial of Progesterone for Acute Traumatic Brain Injury · Annals of Emergency Medicine · 2006 · 484 citations
• CATCH: a clinical decision rule for the use of computed tomography in children with minor head injury · Canadian Medical Association Journal · 2010 · 418 citations
• Clinical Policy: Neuroimaging and Decisionmaking in Adult Mild Traumatic Brain Injury in the Acute Setting · Annals of Emergency Medicine · 2008 · 394 citations
• Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicentre cohort study · Canadian Medical Association Journal · 2011 · 392 citations
• Derivation of the children's head injury algorithm for the prediction of important clinical events decision rule for head injury in children · Archives of Disease in Childhood · 2006 · 380 citations

Most recent work

• Asundexian for Secondary Stroke Prevention · New England Journal of Medicine · 2026
• Cytokines and related signaling pathways in traumatic brain injury · Frontiers in Immunology · 2026
• A Causal and interpretable machine learning framework for postcranioplasty risk prediction and surgical decision support · npj Digital Medicine · 2026
• Autoregulation-Guided Blood Pressure Targets After Stroke Thrombectomy · Neurology · 2026
• The Fast and the Fragile: Neurosurgical Trauma in the Age of Micromobility · PubMed Central · 2026
• Evaluation of near-infrared spectroscopy, transcranial Doppler, and ophthalmic ultrasound measurements in critically Ill pediatric patients with increased intracranial pressure · Frontiers in Pediatrics · 2026
• Measuring optic nerve sheath diameter in children: a simple ultrasound protocol for ICP assessment · Frontiers in Pediatrics · 2026
• Clinical application of regional cerebral oxygen saturation with disturbance coefficient in children with brain functional injury · Frontiers in Pediatrics · 2026
• Artificial intelligence for traumatic brain injury imaging: a translational review from algorithm development to clinical implementation · Frontiers in Neurology · 2026
• Accounting for squared coherence marginally improves the discriminative power of frequency domain cerebral autoregulation markers in surgical aortic valve replacement patients · Medical & Biological Engineering & Computing · 2026

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