Dependence of visual and cognitive outcomes on animal holder configuration in a rodent model of blast overpressure exposure

Retinal gliosis and phenotypic diversity of intermediate filament induction and remodeling upon acoustic blast overpressure (ABO) exposure to the rat eye

“…Vast upregulation of nestin through the cerebral cortex was previously observed in cortical impact TBI, with activation of caspase-3 and apoptosis ( Kaneko et al, 2012 ). However, we do not observe overt retinal degeneration in our rodent ABO model ( Allen et al, 2018 , 2021 ), more consistent with a protective and stabilizing component among the acute gliotic sub-populations we observe post-blast exposure. We cannot rule out an interaction between gliosis and altered retinal function, since optomotor response tracking, to assess visual deficits, measured bi-monthly between 2 and 8 mo post single ABO exposure, revealed significant decreases in spatial frequency and contrast sensitivity in ipsilateral eyes of blast exposed rats compared to matched non-exposed controls in our longitudinal studies, while ERG a-wave and b-waves were not significantly altered post-ABO exposure using the open holder conformation ( Allen et al, 2018 , 2021 ).…”

“…A variety of rodent ABO models have been developed in recent years, ranging from single- or multiple- ABO exposure paradigms, (lapsed or consecutive), low-intensity ( Heyburn et al, 2019 ), or varied-intensity ABO waves ( Harper et al, 2019 ), and either focused ABO directly over the eye globe, with the body constrained, as in many primary blast studies ( Bernardo-Colon et al, 2019 ) or with free head or body movement. Importantly, here we employed an “open” holder configuration, with blast delivered laterally over the right eye and head, allowing unconstrained head movement and ABO-associated coup-contrecoup brain injury—indeed, we found that y-maze performance was compromised revealing long-term cognitive deficits using this open configuration ( Allen et al, 2021 ). While we cannot isolate the primary blast wave effects in this study, ABO with associated head- and coupled eye-movements are usually encountered together in a real-life scenario, and retinal responses to ABO are likely to interact with wider CNS and visual systems effects post exposure.…”

“…The procedures employed for ABO exposure were as described in detail previously (see ( Allen et al, 2018 ; Allen et al, 2021 )). A schematic of the shock-tube apparatus and animal placement is shown in Supplemental Fig.…”

“…S1 . In brief, closed-globe, single ABO exposure to the ipsilateral eye of anesthetized rats was performed using a modified shock tube device ( Allen et al, 2021 ) and an “open”-configuration holder with the head and neck exposed (holder side view, Supplemental Fig. S1A ; housing custom designed and manufactured by Custom Collaborators, Clarence Center, Buffalo, NY).…”

A Long-Term Safety and Efficacy Report on Intravitreal Delivery of Adipose Stem Cells and Secretome on Visual Deficits After Traumatic Brain Injury

“…Both ASCs and ASC-CCM treatment in blast injury significantly alleviated the decrease in visual acuity and increase in contrast sensitivity thresholds after blast injury at five and 10 months, specifically in the left eye being the blast delivery side. Although the underlying mechanism(s) is/are not known concerning the right eye deficits in our model, 28 , 29 recently it has been shown that the type of animal holder used and the compressive forces generated in blast studies affecting visual and cognitive outcomes 28 , 39 , 40 might be involved in our studies. Consequently, left and right eye injuries may have different time course and severities, and different treatment outcomes due to the different bases.…”