Traumatic brain injury (TBI) is a major public health concern affecting 2.8 million people per year in the United States, of whom 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 male mice, using a closed head, single‐impact model of TBI. Six‐week‐old adolescent and 9‐week‐old adult male mice were subjected to mild–moderate TBI. Histological measures for neurodegeneration, gliosis, and microglial neuroinflammation, and behavioral tests of locomotion and memory were performed. Adolescent TBI mice have increased mortality (Χ2 = 20.72, p < 0.001) compared to adults. There is also evidence of hippocampal neurodegeneration in adolescents that is not present in adults. Hippocampal neurodegeneration correlates with histologic activation of microglia, but not with increased astrogliosis. Adults and adolescents have similar locomotion deficits after TBI that recover by 16 days postinjury. Adolescents have memory deficits as evidenced by impaired novel object recognition between 3–4 and 4–16 days postinjury (F1,26 = 5.23, p = 0.031) while adults do not. In conclusion, adults 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 at least 16 days postinjury.

Traumatic optic neuropathy (TON) is commonly associated with head trauma, and thus is a known comorbidity of traumatic brain injury (TBI). TON has not received much attention in basic research despite being associated with permanent vision loss, color blindness, and loss of visual fields. This mini‐review discusses the importance of studying TON in the context of TBI and mechanisms that may be involved in the ongoing optic nerve degeneration of TON. We focus particularly on endoplasmic reticulum (ER) and redox stress processes because of the overlapping presence of these degenerative mechanisms in both TBI and various retinopathies, even though these stress pathways have not yet been used to explain retinal degeneration in a model of TON. We propose that future research is needed to uncover whether ER and redox stress function independently or whether one precedes the other. This understanding is necessary in order to understand the time frames of potential treatment and the prognosis of ongoing secondary effects of TBI including optic nerve injury.

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 options for treatment. Using a murine closed head model of head trauma, we have previously reported in adult mice that there is relatively selective injury to the optic system of the brain. In the current study, we performed blunt head trauma on adolescent C57BL/6 mice, and investigated visual impairment and retinal and optic system injury, using behavioral and histologic methods. After injury, mice display evidence of decreased optomotor responses, as evidence by decreased optokinetic nystagmus responses. There does not appear to be a significant change in circadian locomotor behavior patterns, although there is an overall decrease in locomotor behavior in mice with head injury. There is evidence of axonal degeneration of optic nerve fibers, with associated retinal ganglion cell death. There is also evidence of astrogliosis and microgliosis in major central targets of optic nerve projections. Further, there is elevated expression of markers of endoplasmic reticulum (ER) stress in retinas of injured mice. 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. Visual impairment, histologic markers of gliosis and neurodegeneration, and elevated ER stress marker expression persist for at least 30 days after injury.

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