Citation

Abyadeh M, Gupta V, You Y, Paulo JA, Mirzaei M. Neural Regen. Res. 2025; 20(5): 1399-1400.

Copyright

(Copyright © 2025, Neural Regeneration Research, Shenyang, Liaoning Province, P.R. China, Publisher Wolters Kluwer)

DOI

10.4103/NRR.NRR-D-23-01907

PMID

39075902

Abstract

Traumatic brain injury (TBI) is defined as damage to the brain resulting from an external sudden physical force or shock to the head. It is considered a silent public health epidemic causing significant death and disability globally. There were 64,000 TBI related deaths reported in the USA in 2020, with about US$76 billion in direct and indirect medical costs annually. TBI may have devastating chronic effects on the brain even if clinical symptoms disappear in the short term after the injury. TBI survivors have reported experiencing a range of neuropsychiatric symptoms such as amnesia, varying degrees of visual impairment, and have a higher risk of developing neurodegenerative diseases including Alzheimer's disease (AD) later in their lives (Ramos-Cejudo et al., 2018). TBI has been shown to induce long‐term neuropathological changes in the brain including amyloid‐β (Aβ) deposition and neurofibrillary tangle (NFT) formation (Ramos-Cejudo et al., 2018). Exposure to severe concussion or TBI has been suggested to increase the risk of AD development up to 4.5-fold. It can contribute to progressive cognitive decline which may be evident a decade after the initial injury depending on various factors such as sex, age, intensity, and site of injury (Tsitsopoulos and Marklund, 2013; National Academies of Sciences, Engineering, and Medicine, et al., 2019). Current diagnostic tools have their limitations, especially in detecting mild forms of TBI, without clinical manifestations. Advances in neuroimaging techniques such as positron emission tomography and cerebral spinal fluid evaluation have provided a valuable platform to study brain changes in TBI and associated neurodegeneration. However, time consuming and expensive nature of positron emission tomography and invasive cerebral spinal fluid sampling protocols limit their wide applicability in community settings. Given that any successful intervention to protect the neurons must be applied before a significant damage has occurred, it is imperative to improve the existing diagnostic approaches to detect milder forms of TBI.

Retina is a window to the brain and over the last decade, significant efforts have been made to detect AD-related pathological changes within the retina using retinal scanners. For instance, studies by our group and others have provided the evidence of presence of vascular Aβ deposits, vascular abnormalities, inflammation, intracellular Aβ accumulation, phosphorylated tau protein, NFTs, and retinal ganglion cell degeneration in the retina in AD (Shi et al., 2020). Neurovascular unit integrity is essential for central nervous system function and cerebral vascular abnormalities are considered as early and key factors driving cognitive impairment in AD. Altogether, these studies indicated that evaluating the retinal changes may be a patient-friendly, and noninvasive way to detect and monitor AD. Considering the association between TBI and AD, it has been suggested that TBI-associated chronic changes may have a retinal-specific signature (Figure 1). Currently, several methods can be used to detect signatures of neurodegeneration through the eye, including optical coherence tomography that can measure the thickness of the retinal nerve fiber layer, visual evoked potentials, which measures the electrical activity in the visual cortex in response to visual stimuli. Pupillometry, that assess changes in pupil size and reactivity and provide information about the function of the autonomic nervous system, which may be affected by neurodegenerative processes. Ganglion cell complex analysis, which measures the thickness of the ganglion cell layer in the retina. While the majority of studies concentrate on structural alterations, biochemical changes may appear earlier than structural changes in the eye following TBI, therefore detecting molecular changes in the eye may help to early diagnosis of TBI (Harris et al., 2022). ...

Language: en