Biology subjects

Evanson, N. K.

Publications and source records attributed to Evanson, N. K..

6 recordsLinked to original sources

bioRxiv2025

Delayed protective effect of chronic variable stress on optic tract axonal degeneration after experimental TBI

Of the 2.8 million individuals who seek medical attention for traumatic brain injury (TBI) each year, nearly 300,000 require hospitalization, with up to 60% of these needing intensive care. Intensive care treatment of TBI involves stressful events such as sleep disruption, noise, and painful procedures, potentially leading to chronic stress in patients undergoing such treatment. Given that physiologic stress can exacerbate neuroinflammation and impair normal neural function, we hypothesized that chronic variable stress (CVS) following TBI would exacerbate behavioral and pathological outcomes. We tested this hypothesis by subjecting adolescent male mice to blunt TBI, followed by two weeks of CVS or control conditions. We assessed brain pathologic responses to injury 2-, 5-, 20-, and 28-weeks post-injury. We found chronic optic tract degeneration by Fluoro-jade B staining in TBI groups. Unexpectedly, CVS+TBI mice did not show evidence of optic tract axon degeneration 20 weeks after injury, but did at the other time points. CVS led to increased microglial phagocytic markers early after injury, regardless of TBI status, and TBI led to increased microglial phagocytic markers in a delayed fashion as well. Notably, microglial phagocytosis markers were not elevated in TBI+CVS groups compared to TBI only groups 20 weeks post-injury. There was no effect of TBI or CVS on behavioral measures taken at the end of CVS. These findings suggest a delayed, but not permanent, protective effect on axonal degeneration after TBI, potentially related to altered microglial and astrocytic phagocytic activity.

neuroscience↗

bioRxiv2024

Targeting eIF2α in TBI-induced traumatic optic neuropathy: Effects of Salubrinal and the Integrated Stress Response Inhibitor.

Traumatic brain injury (TBI) can induce traumatic axonal injury in the optic nerve, which is referred to as traumatic optic neuropathy (TON). TON occurs in up to 5% of TBI cases and leads to irreversible visual deficits. TON-induced phosphorylation of eIF2, a downstream ER stress activator in the PERK pathway presents a potential point for therapeutic intervention. For eIF2 phosphorylation can lead to apoptosis or adaptation to stress. We hypothesized that dephosphorylation, rather than phosphorylation, of eIF2 would lead to reduced apoptosis and improved visual performance and retinal cell survival. Adult male mice were injected with Salubrinal (increases p-eIF2) or ISRIB (decreases p-eIF2) 60 minutes post-injury. Contrary to literature, both drugs hindered control animal visual function with minimal improvements in injured mice. Additionally, differences in eIF2 phosphorylation, antioxidant responses, and protein folding chaperones were different when examining protein expression between the retina and its axons in the optic nerve. These results reveal important compartmentalized ER stress responses to axon injury and suggest that interventions in the PERK pathway may alter necessary homeostatic regulation of the UPR in the retina.

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bioRxiv2023

Model matters: Differential outcomes in traumatic optic neuropathy pathophysiology between blunt and blast-wave mediated head injuries.

Over 3 million people in the United States live with long-term disability as a result of a traumatic brain injury (TBI). The purpose of this study was to characterize and compare two different animal models of TBI (blunt head trauma and blast TBI) to determine common and divergent characteristics of these models. With recent literature reviews noting the prevalence of visual system injury in animal models of TBI, coupled with clinical estimates of 50-75% of all TBI cases, we decided to assess commonalities, if they existed, through visual system injury. Blast, repeat blast, and blunt injury were induced in adult male mice to observe and quantify visual deficits. Retinal ganglion cell loss and axonal degeneration in the optic tract, superior colliculus, and lateral geniculate nuclei were examined to trace injury outcomes throughout major vision-associated areas. Optokinetic response, immunohistochemistry, and western blots were analyzed. Where a single blunt injury produces significant visual deficits a single blast injury appears to have less severe visual consequences. Visual deficits after repeat blasts are similar to a single blast. Single blast injury induces contralateral damage to right optic chiasm and tract whereas bilateral injury follows a single blunt injury. Repeat blast injuries are required to see degeneration patterns in downstream regions similar to the damage seen in a single blunt injury. This finding is further supported by Amyloid Precursor Protein (APP) staining in injured cohorts. Blunt injured groups present with staining 1.2 mm of the optic nerve, indicating axonal breakage closer to the optic chiasm. In blast groups, APP was identifiable in a bilateral pattern only in the geniculate nucleus. Evidence for unilateral neuronal degeneration in brain tissue with bilateral axonal ruptures are pivotal discoveries in this model differentiation. Analysis of the two injury models suggest there is a significant difference in the histological outcomes dependent on injury type, though visual system injury is likely present in more cases than are currently diagnosed clinically.

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bioRxiv2023

Brief oxygen exposure after traumatic brain injury speeds recovery and promotes adaptive chronic endoplasmic reticulum stress responses.

Traumatic brain injury (TBI) is a major public health concern particularly in adolescents who have a higher mortality and incidence of visual pathway injury compared to adult patients. Likewise, we have found disparities between adult and adolescent TBI outcomes in rodents. Most interestingly, adolescents suffer a prolonged apneic period immediately post injury leading to higher mortality; so, we implemented a brief oxygen exposure paradigm to circumvent this increased mortality. Adolescent male mice experienced a closed-head weight-drop TBI then were exposed to 100% O2 until normal breathing returned or recovered in room air. We followed mice for 7- and 30-days and assessed their optokinetic response; retinal ganglion cell loss; axonal degeneration; glial reactivity; and retinal ER stress protein levels. O2 reduced adolescent mortality by 40%, improved post-injury visual acuity, and reduced axonal degeneration and gliosis in optic projection regions. ER stress protein expression was altered in injured mice, and mice given O2 utilized different ER-stress pathways in a time dependent manner. Finally, O2 exposure may be mediating these ER stress responses through regulation of the redox-sensitive ER folding protein ERO1, which has been linked to a reduction in the toxic effects of free radicals in other animal models of ER stress.

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bioRxiv2020

Indirect traumatic optic neuropathy after head trauma in adolescent male mice is associated with behavioral visual impairment, neurodegeneration, and elevated endoplasmic reticulum stress markers at acute and subacute times.

Traumatic brain injury (TBI) results in a number of impairments, often including visual symptoms. In some cases, visual symptoms after head trauma are mediated by traumatic injury to the optic nerve, termed traumatic optic neuropathy (TON), which has few effective options for treatment. Using a murine closed-head weight-drop model of head trauma, we have previously reported in adult mice that there is relatively selective injury to the optic tract and thalamic/brainstem projections of the visual system. In the current study, we performed blunt head trauma on adolescent C57BL/6 mice, and investigated visual impairment in the primary visual system, now including the retina, using behavioral and histologic methods at multiple time points. After injury, mice displayed evidence of decreased optomotor responses illustrated by decreased optokinetic nystagmus. There did not appear to be a significant change in circadian locomotor behavior patterns, although there was an overall decrease in locomotor behavior in mice with head injury. There was evidence of axonal degeneration of optic nerve fibers with associated retinal ganglion cell death. There was also evidence of astrogliosis and microgliosis in major central targets of optic nerve projections. Further, there was elevated expression of endoplasmic reticulum (ER) stress markers in retinas of injured mice. Visual impairment, histologic markers of gliosis and neurodegeneration, and elevated ER stress marker expression persisted for at least 30 days after injury. The current results extend our previous findings in adult mice into adolescent mice, provide direct evidence of retinal ganglion cell injury after head trauma, and suggest that axonal degeneration is associated with elevated ER stress in this model of TON.

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bioRxiv2019

Greater neurodegeneration and behavioral deficits after single closed head traumatic brain injury in adolescent vs adult mice

IntroductionTraumatic brain injury (TBI) is a major public health concern affecting 2.8 million people per year, of which about 1 million are children under 19 years old. Animal models of TBI have been developed and used in multiple ages of animals, but direct comparisons of adult and adolescent populations are rare. The current studies were undertaken to directly compare outcomes between adult and adolescent mice, using a closed head, single impact model of TBI.\n\nMethodsSix-week-old adolescent and 9-week-old adult male mice were subjected to TBI using a closed head weight drop model. Histological measures for neurodegeneration, gliosis, and microglial neuroinflammation, and behavioral tests of locomotion and memory were performed.\n\nResultsAdolescent TBI mice have increased mortality (X2= 20.72, p < 0.001) compared to adults. There is also evidence of hippocampal neurodegeneration in adolescents, but not adults. Presence of hippocampal neurodegeneration correlates with histologic activation of microglia, but not with increased markers of astrogliosis. Adults and adolescents have similar locomotion deficits after TBI that recover by 16 days post-injury. Adolescents have memory deficits as evidenced by impaired novel object recognition performance 3 and 16 days post injury (F1,26 = 5.23, p = 0.031) while adults do not.\n\nConclusionsAdults and adolescents within a close age range (6-9 weeks) respond to TBI differently. Adolescents are more severely affected by mortality, neurodegeneration, and inflammation in the hippocampus compared to adults. Adolescents, but not adults, have worse memory performance after TBI that lasts up to 16 days post injury.

neuroscience↗