Traumatic brain injury (TBI) comprises 1/3rd of all injury related deaths in the United States (Prevention, 2022). While mild to moderate severities account for up to 70–90% of emergency department visits for TBI, this number is likely underreported as it only reflects those who seek medical care (Laskowitz and Grant, 2016). More importantly, we know that even mild TBIs, experienced by people who do not traditionally seek emergency assistance, can cause injury to axon tracts found in white matter (Johnson et al., 2013; Vieira et al., 2016). One white matter tract that is particularly vulnerable is the optic nerve, which connects retinal ganglion cells (RGCs) in the eye to the brain (Zwerling et al., 2022). Traumatic injury of the optic nerve is called traumatic optic neuropathy, and, at least in milder cases, this pathology can be difficult to diagnose clinically (Singman et al., 2016).

Although damage to the axons of RGCs is not always the cause of TBI-induced visual deficits (Yu-Wai-Man, 2015), 50–60% of TBI patients across the spectrum of severities and modalities of injury develop some type of visual impairment (Ventura et al., 2014). Animal TBI studies have shed some light on the pathology of traumatic optic nerve injury. For example, exposure to blast overpressures is implicated in fiber degeneration of the ipsilateral optic nerve in rats receiving injury at 129 kPa (Petras et al., 1997). This degeneration was seen in the dorsal lateral geniculate nucleus and superior colliculi. Similarly, blast mediated TBI consistently leads to optic nerve degeneration, decreased thickness of RGC complex, and worsening visual acuity (Evans et al., 2021).

Still, studies of optic nerve damage have most often relied on methods such as optic nerve crush, nerve transection, or ocular blast models. These injury modalities provide critical understanding of the effects of axon and globe injury on the retina but are removed from the context of systemic effects of TBI including inflammation (Burke et al., 2019) or other cortical injury that might occur. However, studying traumatic optic neuropathy in the context of TBI is also complicated by the multiplicity of available experimental TBI models (e.g., controlled cortical impact, fluid percussion, blunt head injury, and blast) (Bolton-Hall et al., 2019; Zhao et al., 2023). Each has its own benefits and limitations for assessing aspects including regional-specific injury, spreading injuries, white matter injury, concussion, or explosive pressurized injuries (Zhao et al., 2023). But there has yet to be a direct comparison of these models to assess whether some may be more optimal for the study of optic nerve injury or whether optic nerve injury is more common than clinically reported.

Thus, it is important to understand that different models may bring varying advantages and disadvantages and can reveal different elements of TBI pathology (Zhao et al., 2023). Exploring the means by which divergent TBI models induce generalizable/overlapping injury pathophysiology (i.e., outcomes associated with secondary injury, such as neuroinflammation, phagocytosis, axonal shearing/degeneration) is one path to understanding similarities among models (McKee and Daneshvar, 2015). We and others have described traumatic axonal injury to the optic nerve and/or optic tracts using various experimental approaches (Bashir et al., 2020; Bernardo-Colon et al., 2019; Evanson et al., 2018; Heldt et al., 2014; Tao et al., 2017; Wang et al., 2013). However, to our knowledge, direct comparisons between animal models of TBI to identify similarities and differences between optic nerve injury across models have yet to be performed. This study aimed to compare two commonly utilized preclinical models of closed-head mild TBI, blunt- and blast-mediated, with the intention of identifying convergent or modality-specific features of injury in the visual system between these injury mechanisms.