Diffuse Axonal Injury: Clinical Prognostic Factors, Molecular Experimental Models and the Impact of the Trauma Related Oxidative Stress. An Extensive Review Concerning Milestones and Advances

Abstract

Traumatic brain injury (TBI) is a condition burdened by an extremely high rate of morbidity and mortality and can result in an overall disability rate as high as 50% in affected individuals. Therefore, the importance of identifying clinical prognostic factors for diffuse axonal injury (DAI) in (TBI) is commonly recognized as critical. The aim of the present review paper is to evaluate the most recent contributions from the relevant literature in order to understand how each single prognostic factor determinates the severity of the clinical syndrome associated with DAI. The main clinical factors with an important impact on prognosis in case of DAI are glycemia, early GCS, the peripheral oxygen saturation, blood pressure, and time to recover consciousness. In addition, the severity of the lesion, classified on the ground of the cerebral anatomical structures involved after the trauma, has a strong correlation with survival after DAI. In conclusion, modern findings concerning the role of reactive oxygen species (ROS) and oxidative stress in DAI suggest that biomarkers such as GFAP, pNF-H, NF-L, microtubule associated protein tau, Aβ42, S-100β, NSE, AQP4, Drp-1, and NCX represent a possible critical target for future pharmaceutical treatments to prevent the damages caused by DAI.

The ratio of serum neuron-specific enolase level to admission glasgow coma scale score is associated with diffuse axonal injury in patients with moderate to severe traumatic brain injury

“…The Glasgow Coma Scale (GCS) is recognized as one of the most important neurological tools for assessing neurological function in patients with TBI ( 15 ). The admission GCS score has been confirmed to be strongly associated with the severity and prognosis of patients with TBI, but it is susceptible to sedation or endotracheal intubation, and patients suffering from DAI may present with lower GCS scores in the acute phase, leading to an inability to accurately distinguish between the grade of DAI and long-term prognosis ( 15 , 16 ).…”

Cognitive impairment in diffuse axonal injury patients with favorable outcome

“…More than 50 million people are suffering from TBI each year worldwide, and most TBI patients are diagnosed by clinical MRI with some degree of DAI, especially severe TBI among them ( Jiang et al, 2019 ; Lammy, 2020 ). DAI manifests in the form of focal axonal shear injuries and axonal breakage, so patients with DAI are more likely to have long-term sequelae or serious neurological deficits, even death ( Lang et al, 2021 ; Palmieri et al, 2021 ).…”

Characterization of Calpain and Caspase-6-Generated Glial Fibrillary Acidic Protein Breakdown Products Following Traumatic Brain Injury and Astroglial Cell Injury

“…There are several limitations of the current study. (i) Since this is a pilot verification study of post-TBI GBDP formation and release, we did not focus on having large enough a sample size to generate clinical results correlation (e.g., how the levels of GBDP in CSF correlate with GCS, CT, or MRI neuropathology outcome, (ii) it will be advantageous to quantify GBDPs by developing GBDP-specific quantitative ELISA—this will enable more quantitative and sensitive assessment of GBDP levels in a wider range of biofluids (such as serum and plasma) [ 52 ]. It is also noteworthy to assess the correlation between GBDP and blood flowing after TBI or other neurological disorders.…”