Search Results (341)

(1) Background: Mild traumatic brain injury (mTBI), the most prevalent form of traumatic brain injury, often results from repetitive impacts to the head and is associated with long-term neurological impairment. The pathophysiology of mTBI is multifactorial and involves alterations in mitochondrial bioenergetics, a key determinant of neuronal function and survival. Although mitochondrial dysfunction is recognized as a hallmark of mTBI, its long-term effects on bioenergetics and the roles of regulatory cytosolic and mitochondrial proteins remain poorly understood. We hypothesized that repeated mTBI (rmTBI) induces sustained deficits in mitochondrial bioenergetics that are associated with long-term changes in key bioenergetic and other regulatory proteins. (2) Methods: Using the repeated CHIMERA injury model in adult male rats, randomly assigned to sham or rmTBI groups, we assessed mitochondrial respiration in isolated mitochondria and whole cerebral cortex homogenates using a Clark O₂ electrode and an Oroboros O₂k respirometer at time points ranging from 1 day to 2 months post-injury. Western blotting was performed for expression of regulatory proteins HKI, DRP1, MFN2, VDAC1, and ANT2. (3) Results: At 2 months post-rmTBI, respiration was faster and uncoupled, while ATP synthesis was significantly slowed compared with sham rats. This was accompanied by decreased expression of mitochondrial MFN2 and ANT2, by increased mitochondrial expression of DRP1, and by decreased translocation of HKI to mitochondria. There was no significant difference in VDAC1 expression. Earlier time points showed no significant differences in bioenergetics or protein expression, but neuro-inflammatory markers (GFAP and Iba1) were significantly elevated at these earlier time points of post-injury. (4) Conclusions: These findings indicate that rmTBI leads to a delayed long-term impairment of mitochondrial bioenergetics associated with alterations in proteins critical for bioenergetic regulation and mitochondrial control. This suggests a pathophysiologic mechanism for the persistent cognitive and behavioral deficits observed following rmTBI. Full article

Mild traumatic brain injury (mTBI) contributes substantially to years lived with disability (YLD), decreases health-related quality of life, and imposes significant costs on healthcare systems and society. Millions of people experience mTBI each year, and healthcare costs for mTBI in just the first year after injury exceed $44 billion USD. Despite the common occurrence of mTBI, estimates of incidence, prevalence, related disability, and costs vary widely. This variance is attributed to the underreporting of head impacts, inconsistent definitions of mTBI, and a lack of objective biomarkers. Currently available clinical blood biomarkers primarily assist in ruling out CT-detectable intracranial injury rather than definitively diagnosing mTBI itself, underscoring the continued need for objective, portable, and clinically specific biomarkers. Numerous imaging findings, blood proteins, and physiological measures are under investigation for these purposes, and some may have multiple uses. Specific biomarkers for acute diagnosis are needed urgently. Although many systematic reviews have been published, most focus on a single biomarker or class of biomarkers. Given the breadth of potential biomarker categories, conducting a comprehensive, systematic review across modalities is challenging. Here, we provide a narrative review summarizing the extant literature across major biomarker domains studied in adolescents and adults. We emphasize candidates supported by the most robust evidence to guide continued research and clinical translation. Full article

Astrocytes undergo pronounced reactivity during traumatic brain injury (TBI); however, the temporal dynamics of this response and the signaling mechanisms regulating astrocyte proliferation remain incompletely defined. In this study, we characterized the spatiotemporal profile of astrocyte reactivity and proliferation in the hippocampus during TBI and investigated the involvement of mammalian target of rapamycin complex 1 (mTORC1) signaling in these processes. Using a mouse model of TBI, we found that injury triggered a rapid astrocytic response in the hippocampus, characterized by increased glial fibrillary acidic protein (GFAP) expression and morphological hypertrophy as early as 4 h post-injury. Astrocyte proliferation emerged subsequently, peaked during the acute phase (48 and 72 h), and declined to baseline levels at 7 days post-trauma, indicating a transient proliferative response during TBI. Concurrently, mTORC1 signaling was robustly activated in reactive astrocytes in the hippocampus and was specifically associated with proliferative reactive astrocytes during injury. Pharmacological inhibition of mTORC1 signaling with rapamycin significantly reduced reactive astrocyte proliferation during TBI without altering astrocytic hypertrophy. Together, these findings demonstrate that TBI induces a rapid but transient astrocyte activation and proliferation response in the hippocampus and that mTORC1 activation is required for the proliferation, but not the hypertrophic activation, of reactive astrocytes during traumatic brain injury. Full article

Background: Mild traumatic brain injury (mTBI) is frequently associated with persistent cognitive and psychosocial symptoms, yet biological correlates of recovery remain poorly understood, particularly among Asian and Pacific Islander (API) populations. Pre-injury psychosocial adversity may further shape post-injury recovery trajectories. This pilot study examined associations between participation in a 2-week, home-based, dual-task cognitive–walking intervention (Daily Brain Exercise; DBE) and changes in cognitive, psychological, and salivary microRNA (miRNAs) measures among APIs with and without a self-reported history of mTBI. Methods: API participants completed remote cognitive testing (CNS Vital Signs), psychosocial assessments (Neuro-QoL), and saliva collection before and after DBE participation. Salivary RNA was purified, and miRNA expression was profiled using nCounter^® Human v3 miRNA Expression Panels (NanoString). Differential expression analyses were conducted using ROSALIND^® platform (OnRamp Bioinformatics, San Diego, CA, USA), a cloud-based bioinformatics analysis system, to calculate fold changes and p-values. Pre-injury psychosocial adversity was assessed via the Trauma History Screen and examined descriptively as a contextual modifier of functional outcomes. Results: Twenty-one APIs (mean age 22.9 years; 76.7% female) were enrolled, including 14 individuals with a self-reported history of mTBI (mean 4.64 years post-injury; 50% with multiple injuries). Following DBE participation, increases in cognitive flexibility and executive function scores were observed in both mTBI and control groups. Additional increases in psychomotor speed, processing speed, sleep disturbance, and depressive symptoms were observed descriptively within the mTBI group. Subgroup analyses suggested variability in pre–post patterns across combinations of mTBI history and pre-injury psychosocial adversity. Exploratory miRNA analyses identified seven miRNAs that were differentially expressed in the mTBI group following DBE (unadjusted p < 0.005), including hsa-miR-7-5p, previously reported in association with neurodevelopmental and neurological pathways. Conclusions: In this pilot, feasibility-focused study, participation in a brief, home-based, dual-task intervention was associated with descriptive changes in selected cognitive and psychosocial measures among APIs, particularly those with a history of mTBI and pre-injury adversity. The observed subgroup patterns warrant confirmation in adequately powered, controlled studies. Exploratory changes in salivary miRNAs co-occurred with functional improvements, thus generating a hypothesis for a future investigation. Full article

Background: Tuberculosis (TB) remains a major global health challenge, with Mycobacterium tuberculosis (M. tuberculosis) causing significant morbidity and mortality mainly in high-burden countries. Following exposure to M. tuberculosis, individuals may become infected, developing TB infection (TBI) through inhalation of the bacillus: this affects approximately one-fourth of the global population and serves as a critical reservoir for potential disease reactivation and transmission. The risk of being infected with M. tuberculosis is shaped by bacterial load of people with TB, contact patterns, environmental factors, and host susceptibility, particularly in high-risk congregate settings. Elucidating these determinants is instrumental for optimising TB prevention and control strategies. Methods: A preliminary PubMed search was conducted on 25 August 2024, using the keywords “latent tuberculosis infection,” “risk factors,” and “systematic review.” Targeted reviews were then performed in November 2024 to examine factors influencing progression from exposure to M. tuberculosis to TBI. Systematic reviews published between January 2000 and November 2024 were included. Results: The scoping review analysed eight systematic reviews, grouping findings into three key themes: (1) proximity and behavioural risk factors; (2) environmental risk factors; and (3) host immune vulnerabilities. Close contact with people with TB in crowded settings, such as dormitories, healthcare facilities, and prisons, was strongly associated with an elevated risk of TBI. Healthcare workers travelling from low- to high-incidence regions faced the highest risk due to frequent exposure to M. tuberculosis, while military personnel and general travellers had lower risks. Environmental exposures, including second-hand smoke and inadequate ventilation, further heightened susceptibility among children and adults. Host immune risk factors, such as advanced age, low body mass index, lack of BCG vaccination, and metabolic disorders such as diabetes, markedly increase susceptibility to TBI. The interplay between proximity, behavioural and environmental risk factors, and host immune vulnerabilities highlights the multifactorial nature of TBI risk. Conclusion: Effective TBI control demands a multifaceted approach, combining robust infection prevention and control measures, comorbidity management, and mitigation of behavioural risk factors like smoking. Tailored strategies are crucial for high-risk settings such as healthcare facilities and prisons. Multisectoral collaboration is essential to address key risk factors and protect vulnerable populations from progressing to TBI. Full article

Background/Objectives: Over the last two decades, there has been a substantial change in the understanding of post-traumatic hypopituitarism (PTHP), which is no longer regarded as a marginal phenomenon. Clinical manifestations of pituitary hormone deficiency are frequently nonspecific, with fatigue and cognitive dysfunction predominating. Given that head injuries currently constitute a global burden for healthcare systems, the aim of the present study was to determine whether self-reported post-mild traumatic brain injury (mTBI) symptoms that may indicate hypopituitarism reflect true pituitary insufficiency or are attributable to other hormonal aberrations. The study aimed to assess the relationship between self-reported symptoms of PTHP and hormonal test results following mTBI. Setting: Patients were recruited from a tertiary trauma center Emergency Department (ED) in northern Poland from January 2023 to October 2025. Participants: The participants were adult (18 > y.o.) individuals with mTBI who met the inclusion criteria. Design: This was a prospective cohort study. During their post-head injury admission to the ED, patients had a blood sample taken. The procedure was repeated consecutively after 3, 6 and 12 months. After 6 and 12 months, patients were asked to complete a questionnaire. Methods: Pituitary and thyroid hormones were measured using the chemiluminescence immunoassay method and the heterogenous immunochemiluminescence method. The questionnaire used, Questionnaire for the Assessment of Symptoms of Anterior Pituitary Insufficiency in Patients After Mild Traumatic Brain Injury (mTBI) Hospitalized in the Emergency Department, was designed for the purposes of this study. Results: Self-reported symptoms suggestive of anterior pituitary dysfunction following mTBI were not confirmed by laboratory assessment of pituitary hormones. However, after 6 months, a statistically significant correlation was found between the number of reported symptoms and prolactin levels (ρ = 0.730; p = 0.0013), whereas after 12 months a downward trend in free triiodothyronine (fT3) levels was observed compared with the baseline. Conclusions: Persistent symptoms reported by patients following mTBI at 6 and 12 months, particularly fatigue and impaired concentration, showed statistical associations with prolactin levels at 6 months and lower fT3 levels at 12 months. These findings reflect correlations identified in the statistical analysis and do not support inferences regarding causality or the presence of true PTHP. Full article

Background: Traumatic head injury (THI) includes a diverse range of hemorrhagic brain lesions (HBL), which are distinct phenotypes with characteristic pathophysiological mechanisms. Computed tomography (CT) is the cornerstone of the initial assessment and diagnosis; however, its sensitivity is limited, especially in mild head injury. Blood-derived biomarkers, including Neuron-Specific Enolase (NSE) and S-100B, have been extensively studied; however, their efficacy in distinguishing HBL subtypes remains unclear. We evaluated whether circulating serum levels of S-100B and NSE can discriminate between distinct intracranial HBLs and extracranial hemorrhagic lesions (ECH). Methods: This is an interim analysis of a prospective, randomized, double-blind clinical trial including 434 adult patients with blunt THI. HBL phenotypes identified by CT scan included subarachnoid hemorrhage (SAH), subdural hematoma (SDH), epidural hematoma (EDH), and brain contusion (BC). Unique lesions were considered while overlapping lesions were excluded. Subgaleal hematoma (SGH) was included as an example of ECH. Serum S-100B was assessed within 6 h post-injury, while serum NSE was evaluated at admission, 24 h, and 48 h thereafter. Serum NSE and inflammatory cytokines were quantified in duplicates using a Human Magnetic Luminex 5-plex assay, while serum S-100B concentrations were measured separately. Serum epinephrine concentrations were quantified using an ELISA. Biomarker profiles were analyzed based on lesion phenotype, lesion multiplicity, injury pattern, and clinical outcomes, including hospital length of stay (HLOS) and the Glasgow Outcome Scale—Extended (GOSE). Results: Admission median S-100B levels were higher in patients with SAH (495 pg/mL) and lower in those with SGH (191 pg/mL); however, they did not show statistically significant difference among HBL phenotypes. They were significantly higher in patients with polytrauma TBI (420 pg/mL) compared to isolated TBI (258 pg/mL). Baseline and 48 h NSE concentrations were significantly higher in SDH (25,089 and 28,438 pg/mL) than in other THI lesions (p = 0.04). There were no statistically significant changes in NSE values over time across all THI lesions except for SDH in which they raised more after 48 h (p = 0.02). They had a significant drop in polytrauma over the time (p = 0.001). Compared to intracranial lesions, S-100 B levels were significantly lower in SGH and in skull fractures without intracranial hematomas. Both S-100B and NSE levels were elevated in individuals with unfavorable GOSE scores. Conclusions: In this secondary exploratory analysis, elevated serum NSE and S-100B levels discriminate between extra- and intracranial lesions and appear to represent distinct but complementary aspects of THI, indicating neuronal damage and its temporal evolution, and predicting clinical and functional outcomes. The present findings reflect association and not causation. Future studies incorporating larger or multicenter cohorts, volumetric imaging, and long-term outcomes are required to validate and refine biomarker-guided algorithms for personalized THI care. Full article

Background: Diabetic foot ulcers (DFUs) are considered a prevalent complication of diabetes mellitus, frequently accompanied with compromised peripheral circulation, slower healing, as well as high risk of infection in addition to risk of amputation. Additional treatments that enhance microvascular perfusion and lessen plantar pressure may accelerate the healing process. This study was carried out to examine the impact of pulsed electromagnetic field (EMF) therapy as well as customized silicone gel insoles in terms of peripheral circulation in addition to vascular indices in patients with DFUs. Methods: A randomized, controlled clinical trial, including sixty-six adults diagnosed with type II diabetes as well as plantar DFUs (Wagner grade I–II) were divided into three groups (n = 22 each): Group A was given low-frequency electromagnetic field therapy (15–50 Hz, 2–5 mT, 30 min, three times per week for 8 weeks), Group B was given a customized silicone gel insoles produced for ulcer offloading, and Group C (control) was given conventional physiotherapy along with wound care. Peripheral microcirculation as well as tissue perfusion were the primary outcomes, and they were measured using Laser Doppler Flowmetry (LDF), Photoplethysmography (PPG), in addition to the Toe–Brachial Index (TBI). The secondary outcome included the Ankle–Brachial Pressure Index (ABPI). A blinded assessor measured the outcomes at the beginning of the study, after the intervention (week 8), and again after the follow-up (week 16). Results: EMF therapy significantly improved LDF (baseline: 45.2 ± 6.5 PU; week 8: 62.5 ± 7.2 PU), PPG (0.42 ± 0.08 mV to 0.68 ± 0.10 mV), TBI (0.64 ± 0.07 to 0.82 ± 0.08), and ABPI (0.88 ± 0.06 to 0.97 ± 0.05) compared with insoles and controls (p < 0.001, partial η² 0.25–0.37). The insole group exhibited moderate enhancements, whereas the control group demonstrated minor changes. Between-group analyses showed substantial differences in favor of EMF therapy across all measured variables (F = 13.5–19.9, p < 0.001). Improvements continued at the 8-week follow-up. Conclusions: Patients with DFUs who receive EMF therapy experience a significant improvement in their peripheral microcirculation, tissue perfusion, as well as vascular indices. This is more effective than just mechanical offloading, and custom insoles offer extra benefits by redistributing pressure. Combining EMF therapy with regular DFU care may speed up healing and lower the risk of problems. Additional research should investigate the efficacy of combined EMF as well as off-loading interventions and their long-term outcomes. Full article

Mild traumatic brain injury (mTBI) in adults is extremely common worldwide, but only a small fraction of these patients harbor clinically significant intracranial injuries. Computed tomography (CT) of the head is the standard diagnostic tool to detect traumatic brain hemorrhages or lesions, yet indiscriminate CT scanning of all mTBI patients is inefficient, costly, and exposes patients to ionizing radiation. To optimize patient care, numerous clinical decision rules and guidelines have been developed internationally to identify which adult patients with mTBI should undergo head CT. This review provides a global perspective on the indications for head CT in adult mTBI, comparing key decision rules including the Canadian CT Head Rule, New Orleans Criteria, UK NICE Head Injury Guidelines, and others. Methods: We conducted a comprehensive analysis of major international guidelines and decision rules for head CT in adult mTBI, focusing on their inclusion criteria, risk factors, and diagnostic performance. Results: All the examined rules prioritize near-100% sensitivity for identifying patients who need neurosurgical intervention, but they differ greatly in specificity and recommended CT utilization rates. North American rules such as the New Orleans Criteria tend to favor higher sensitivity, scanning almost all patients with any symptom, whereas the Canadian CT Head Rule and certain European guidelines (NICE, Scandinavian) are more selective, significantly reducing CT usage while maintaining safety. Discussion: We discuss how these variations reflect different healthcare settings and risk tolerances, and we examine the implications for neurosurgical practice. We also highlight challenges in guideline implementation, the impact on global CT utilization, and emerging approaches (such as biomarker-assisted triage) that may further refine decision-making. In conclusion, appropriate use of clinical decision rules for head CT in mTBI can safely minimize unnecessary imaging, but local adaptation and clinician judgment remain crucial to ensure that no significant injuries are missed while avoiding over-scanning. Full article

Mild traumatic brain injury (mTBI) is typically associated with transient cognitive disturbance, particularly involving attention and new learning, with most patients demonstrating full recovery within weeks. Memory impairment in uncomplicated mTBI generally reflects reversible neurometabolic dysfunction and is limited to a brief period of post-traumatic amnesia and restricted retrograde loss surrounding the injury. However, a subset of patients develop persistent and disproportionate autobiographical memory disturbance that exceeds expected neuroanatomical limits and lacks structural correlates on neuroimaging. In rare but clinically challenging cases, this presentation may resemble extensive retrograde or identity-related amnesia. This review examines functional (dissociative) amnesia emerging after mTBI and proposes that concussion may act as a gateway condition facilitating the development of Functional Cognitive Disorder (FCD) in vulnerable individuals. We differentiate expected post-traumatic memory patterns from atypical selective impairment of autobiographical retrieval and clarify how distinct memory systems—episodic, autobiographical, semantic, and procedural—are differentially affected. We expand the two-hit hypothesis by integrating contemporary neurobiological evidence. The first hit comprises concussion-induced neurometabolic disturbance, glial activation, oxidative imbalance, and transient fronto-limbic dysregulation. The second hit may involve psychological stress, identity threat, maladaptive metacognitive processes, or persistent neuroinflammatory signalling, collectively resulting in functional inhibition of autobiographical memory retrieval despite preserved memory storage. Functional amnesia is conceptualised as a severe phenotype within the spectrum of functional cognitive disorder. We introduce a structured clinician-administered interview (SIFRA) to operationalise diagnostic features and support systematic assessment. This integrative framework reconciles neurological vulnerability with functional network dysregulation and provides a coherent basis for diagnosis and multidisciplinary management of persistent memory disturbance after mTBI. Full article

Background/Objectives: Mild traumatic brain injury (mTBI) is the most common subtype of traumatic brain injury, where patients experience a multitude of symptoms from headaches to memory loss and mood changes. Consequently, there are known poor prognostic factors for mTBI that can impede recovery and alter management courses. This narrative review aims to synthesize and provide a critical assessment of the current diagnostic criteria, management, and prognostic factors for mTBI to inform practice guidelines. Methods: This study adopts a patient-centered approach, focusing on treating presenting symptoms and referring patients to specialists for abnormal exam findings as needed. These findings are based on a narrative review of existing literature and the medical opinions of experts in neurology, physical medicine and rehabilitation, and pain medicine. The evidence supports that there are patient-related, injury-related, and contextual psychosocial factors that further complicate the long-term prognosis and management of mTBI. Conclusions: mTBI is defined by a set of diagnostic criteria: post-traumatic amnesia (PTA) lasting no longer than 24 h, loss of consciousness (LOC) not exceeding 30 min when present, and a Glasgow Coma Scale (GCS) score between 13 and 15. Current treatment options include prescribed rest followed by a gradual return to physical activity, medication management for symptoms with cognitive behavioral therapy, or vestibular physical therapy. Notably, several of these diagnostic criteria overlap with known poor prognostic indicators. These prognostic factors can be grouped into three categories: injury-related factors (LOC, positive imaging findings, history of prior concussions, and high symptom burden); patient-related factors (demographic characteristics and psychiatric history); and contextual psychosocial factors. Full article

Background: Traumatic brain injury (TBI) frequently leads to long-term neurological deficits. Recent research also implicates cellular senescence—a state of permanent cell cycle arrest driven by DNA damage—as a key contributor to neuroinflammation and cognitive decline. This study investigates the cell-type specificity of senescence within glial and vascular cells of the neurovascular unit (NVU) following experimental TBI in a rat model. Methods: Rats underwent various TBI scenarios, including single severe TBI (sTBI), single mild TBI (mTBI), repetitive mild TBI (rmTBI) and repetitive sham-operated control (rSham). Twenty-four hours or four weeks later, brains were harvested and brain sections were co-stained for γH2AX and cell type-specific markers. Immunofluorescence microscopy was used to comprehensively assess senescence in both glial and vascular cells of the NVU, specifically astrocytes, microglia, endothelial cells, and pericytes. Results: We observed acute increased astrocyte senescence in sTBI samples and microglial senescence in mTBI and sTBI samples in the neocortex, while endothelial cell senescence was significantly elevated in the neocortex of the sTBI group after four weeks. Pericytes did not exhibit significant signs of senescence at either time point. Conclusion: These findings demonstrate differential γH2AX labelling of NVU components following TBI, suggesting that vulnerability to TBI-induced senescence can be specific both to the cell type and the time after the injury. This has implications on therapies targeting senescent cells for mitigating the long-term consequences of TBI. Full article

Serum ferritin (Ft) reflects total body iron stores and serves as a reference indicator for iron supplementation. However, optimal Ft level remains unclear in hemodialysis (HD) patients. We previously reported that total body iron (TBI), a novel index defined as the sum of red blood cell iron and storage iron, increases during oral iron replacement therapy (OIRT) and remains stable once iron sufficiency is achieved. In this study, we analyzed data from 100 OIRT courses in 79 maintenance HD patients. We examined the relationship between changes in hemoglobin (Hb) and Ft (⊿Hb, ⊿Ft) at 4 and 7 months after the initiation of OIRT, during which TBI remained stable, to determine the Ft level required for erythropoiesis. At 7 months, compared with 4 months, mean Hb significantly decreased by 0.2 g/dL (p = 0.03), while median Ft significantly increased from 60 to 75.0 ng/mL (p < 0.01). After adjustment for TBI, a significant inverse relationship was observed between ⊿Hb and ⊿Ft (β = −35.9, 95% CI −40.1 to −31.7, p < 0.001). These results indicate that an increase of 1 g/dL in Hb requires approximately 30–40 ng/mL of Ft, suggesting that this threshold may be useful for guiding iron supplementation in the treatment of anemia. Full article

Cold-inducible RNA-binding protein (CIRP) is a critical molecule in the central nervous system (CNS) with functions that depend on its subcellular localization, exhibiting biphasic regulatory roles in both physiological and pathological processes. Under physiological conditions, intracellular cold-inducible RNA-binding protein (iCIRP) contributes to the maintenance of circadian rhythms by regulating the stability of core clock gene mRNAs and exerts neuroprotective effects during mild hypothermia by preserving the blood–brain barrier and inhibiting apoptosis. Pathologically, extracellular cold-inducible RNA-binding protein (eCIRP) functions as a damage-associated molecular pattern (DAMP) that drives neuroinflammation and brain injury. In ischemic stroke (IS), eCIRP promotes neutrophil extracellular trap (NET) formation and increases microglial activity via the Toll-like receptor 4 (TLR4) pathway. In cerebral ischemia–reperfusion (I/R) injury, eCIRP activates oxidative stress and the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome through the TLR4 axis, exacerbating mitochondrial damage. In intracerebral hemorrhage (ICH), eCIRP further amplifies inflammation via the interleukin-6 receptor (IL-6R)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In traumatic brain injury (TBI), eCIRP activates the endoplasmic reticulum stress pathway, intensifying apoptosis. In Alzheimer’s disease (AD), eCIRP regulates tau phosphorylation and β-amyloid (Aβ) metabolism and may mediate the link between alcohol exposure and AD pathology. Preclinical studies indicate that serum eCIRP levels correlate with IS and ICH severity, highlighting its potential as a biomarker. This systematic review elucidates the mechanisms of CIRP in CNS diseases, providing insights for understanding and preventing conditions such as IS, cerebral I/R injury, ICH, TBI, and AD. Full article

Background: Routine admission inflammatory and metabolic biomarkers have been proposed as adjunctive tools in mild traumatic brain injury (mTBI). However, their association with specific traumatic intracranial lesion types remains unclear. Methods: We conducted a prospective observational study including adult patients with isolated mTBI who underwent head computed tomography (CT) on admission. Admission laboratory parameters included the platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and glucose-to-potassium ratio (GPR). Two predefined endpoints were assessed. The first compared biomarker values between CT-positive and CT-negative patients. The second evaluated associations between biomarkers and individual intracranial lesion subtypes, including analyses restricted to isolated lesions. Results: A total of 125 patients were included, of whom 95 (76%) were CT-positive. No significant differences were observed between CT-positive and CT-negative patients for PLR (p = 0.793), GPR (p = 0.531), or SII (p = 0.291). In lesion-specific analyses including all intracranial injuries, subdural hematoma (SDH) was associated with higher GPR compared with patients without SDH (p = 0.016). In analyses restricted to patients with isolated lesions, SDH was associated with higher PLR (p = 0.018) and higher GPR (p = 0.015). No significant associations were observed between any biomarker and intraparenchymal hemorrhage, subarachnoid hemorrhage, or epidural hematoma (all p > 0.05). Patients with multiple intracranial injuries exhibited higher PLR (p = 0.012) and higher SII (p = 0.021) compared with those with isolated lesions. After correction for multiple comparisons, none of the observed associations remained statistically significant. Conclusions: These findings suggest that routine systemic biomarkers have limited global discriminatory value in mTBI. Exploratory lesion-specific associations with SDH did not remain significant after correction for multiple comparisons, underscoring the preliminary nature of these findings. Full article