Editorial: Neurodegeneration and Cognitive Impairment after Traumatic Brain Injury: Primum Non Nocere

Tao Liu ¹ Li Ma ² Yu Chen ³ Rongcai Jiang ^4*

• ¹ Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
• ² Department of Neurosurgery, university of Pittsburgh Medical Center Pittsburgh, Pittsburgh, United States
• ³ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
• ⁴ Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, Beijing Municipality, China

Injury: Primum Non Nocere Traumatic brain injury (TBI) remains a critical public health concern. Despite advancements in acute care and trauma management that have improved survival rates, the long-term effects, including neurodegeneration and cognitive decline, pose substantial challenges. 1 TBI initiates a cascade of pathological processes that extend beyond the primary injury, resulting in progressive and enduring damage. Secondary injury, such as inflammation, oxidative stress, and excitotoxicity, are central drivers of neurodegeneration and may lead to chronic traumatic encephalopathy (CTE), Alzheimer's disease, and other neurodegenerative disorders. Growing evidence also underscores the cumulative damage caused by repeated mild TBI (mTBI), highlighting the urgent need for greater awareness and targeted research to address its long-term consequences. 1 The causes of deficits following TBI are complex and multifactorial, involving direct These include edaravone dexborneol, oxiracetam, piracetam, and compound porcine cerebroside injection, offering encouraging advancements for patient care. [2][3][4][5][6][7] The brain's lymphatic drainage system, comprising the glymphatic system and meningeal lymphatic vessels (MLVs), plays a vital role in clearing waste after TBI.Recent research has focused on targeting this system to enhance cognitive recovery and overall outcomes. 8,9 Zhuo et al. suggested that glymphatic imaging markers, such as the enlarged perivascular space (ePVS) burden and the ALPS index, may provide valuable insights into TBI recovery and guide targeted interventions. Similarly, Qin et al. proposed that low-frequency amplitude (ALFF) analysis using resting-state functional MRI (rs-fMRI) could help predict treatment outcomes in patients with disorders of consciousness. These studies reinforce the potential of advanced neuroimaging and biomarkers for early diagnosis, monitoring, and precise management of TBI-related neurodegeneration.Chronic subdural hematoma (cSDH) often occurs after mild brain injury, which may lead to cognitive impairment. cSDH has long been a subject of research interest, particularly following two recent randomized controlled trials (RCTs) in The New England Journal of Medicine exploring middle meningeal artery embolization as a treatment option. 10,11 These studies sparked debate over whether surgery is necessary for patients with mild or non-progressive symptoms. For decades, surgery has been the mainstay treatment for cSDH, offering symptom relief but carrying risks, including mortality and a 10% recurrence rate. 12 cSDH primarily affects older adults, and in low-and middle-income countries, the financial burden of surgery remains a major obstacle. This has fueled global efforts to identify effective non-surgical alternatives, particularly for patients unable to undergo surgery. A 2018 RCT published in JAMA Neurology highlighted atorvastatin as a promising non-surgical therapy for cSDH, sparking significant interest. 13 Statin therapy is now widely used in China, and ongoing real-world studies are expected to provide further evidence, offering hope for improved treatment strategies. 14 The discussions surrounding cSDH reflect broader challenges in TBI management, a field that remains riddled with unresolved questions. However, optimism persists as ongoing research seeks to optimize care. In the acute phase, balancing intracranial pressure monitoring and surgical interventions to reduce mortality while preventing long-term neurological impairments is a key clinical focus. Similarly, during rehabilitation, pharmacological treatments and cognitive training must be carefully tailored to avoid causing further harm to the nervous system. Adhering to the principle of "Primum Non Nocere", also called first, do no harm; while prioritizing individualized care and scientific rigor is essential for improving long-term outcomes for TBI patients.In summary, the relationship between TBI and neurodegenerative diseases remains a critical area of research, with significant knowledge gaps surrounding mechanisms, diagnostics, treatments, and individual variability. The roles of genetic, biological, and environmental factors in TBI-related neurodegeneration are still poorly understood.Additionally, the sequence, rate, and extent of neuropathological progression or resolution remain speculative due to the lack of sensitive and specific biomarkers.Exploring the interplay between TBI complications and neurodegeneration is crucial for advancing the field. Addressing the complexities of TBI requires interdisciplinary collaboration and global research initiatives. Continued innovation and collective efforts are essential to uncover effective solutions, bringing us closer to addressing this pressing public health challenge and improving outcomes for affected individuals worldwide.