Specific serum metabolites can differentiate severe and mild human traumatic brain injury

Traumatic Brain Injury (TBI) is a prevalent neurological condition with significant public health implications. The heterogeneity in TBI's pathophysiology presents challenges in diagnosis and prognosis, highlighting the need for sensitive and specific biomarkers. Metabolomic studies have emerged as a promising approach to identify such biomarkers.

This study aimed to define the serum metabolome in patients with acute TBI and to identify metabolites that could differentiate severe from mild TBI, potentially serving as novel biomarkers for diagnosis and prognosis.

We conducted a metabolomic analysis on 12 severe TBI patients, 33 mild TBI patients, and 30 healthy controls. Blood samples were collected within 24 h post-injury, and metabolomic profiling was performed using LC-MS/MS and GC-MS. Data preprocessing and statistical analysis were conducted using Progenesis QI software, followed by Random Forest analysis and ROC curve assessments for metabolite selection and validation.

The serum metabolome of TBI patients significantly differed from non-TBI patients, with distinct metabolic signatures correlating with injury severity. Methoxyamine was identified as a potential biomarker, showing increased levels in severe TBI compared to mild TBI and healthy controls. In the random forest analysis, methoxyamine was ranked among the top discriminating metabolites between severe and mild TBI, achieving an AUC of 0.8333 in the testing dataset. Network toxicology and molecular docking suggested a potential interaction between methoxyamine and HSP90AA1, a protein associated with TBI severity as well.

Our findings indicate that specific serum metabolites, particularly methoxyamine, may serve as novel biomarkers for differentiating severe from mild TBI. Further research is warranted to explore their potential as therapeutic targets and their role in TBI pathophysiology.