Astrocytic degeneration in chronic traumatic encephalopathy

Hsu, Eric T.; Gangolli, Mihika; Su, Shiran; Holleran, Laurena; Stein, Thor D.; Alvarez, Victor E.; McKee, Ann C.; Schmidt, Robert E.; Brody, David L.

doi:10.1007/s00401-018-1902-3

Cited by 55 publications

(52 citation statements)

References 68 publications

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“…This astrocyte pathology has been observed in AD, Binswanger's mixed dementia, aging, and ischemic brain tissues [43][44][45][46][47]. Furthermore, recent evidence in postmortem analyses of chronic traumatic encephalopathy (CTE) has demonstrated trauma-induced accumulation of a morphologically distinct subset of reactive astrocytes [48]. Characteristically, these astrocytes had a beaded "pearl on a string" degenerative morphology.…”

Section: Tbi Elicits Delayed Reactive Gliosis That Is Protracted In Tmentioning

confidence: 84%

Effects of advanced age upon astrocyte-specific responses to acute traumatic brain injury in mice

Early

Gorman

Eldik

et al. 2020

J Neuroinflammation

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Background: Older-age individuals are at the highest risk for disability from a traumatic brain injury (TBI). Astrocytes are the most numerous glia in the brain, necessary for brain function, yet there is little known about unique responses of astrocytes in the aged-brain following TBI. Methods: Our approach examined astrocytes in young adult, 4-month-old, versus aged, 18-month-old mice, at 1, 3, and 7 days post-TBI. We selected these time points to span the critical period in the transition from acute injury to presumably irreversible tissue damage and disability. Two approaches were used to define the astrocyte contribution to TBI by age interaction: (1) tissue histology and morphological phenotyping, and (2) transcriptomics on enriched astrocytes from the injured brain. Results: Aging was found to have a profound effect on the TBI-induced loss of astrocyte function needed for maintaining water transport and edema-namely, aquaporin-4. The aged brain also demonstrated a progressive exacerbation of astrogliosis as a function of time after injury. Moreover, clasmatodendrosis, an underrecognized astrogliopathy, was found to be significantly increased in the aged brain, but not in the young brain. As a function of TBI, we observed a transitory refraction in the number of these astrocytes, which rebounded by 7 days postinjury in the aged brain. Transcriptomic data demonstrated disproportionate changes in genes attributed to reactive astrocytes, inflammatory response, complement pathway, and synaptic support in aged mice following TBI compared to young mice. Additionally, our data highlight that TBI did not evoke a clear alignment with the previously defined "A1/A2" dichotomy of reactive astrogliosis. Conclusions: Overall, our findings point toward a progressive phenotype of aged astrocytes following TBI that we hypothesize to be maladaptive, shedding new insights into potentially modifiable astrocyte-specific mechanisms that may underlie increased fragility of the aged brain to trauma.

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Section: Tbi Elicits Delayed Reactive Gliosis That Is Protracted In Tmentioning

confidence: 84%

Effects of advanced age upon astrocyte-specific responses to acute traumatic brain injury in mice

Early

Gorman

Eldik

et al. 2020

J Neuroinflammation

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show abstract

“…This astrocyte pathology has been observed in AD, Binswanger's mixed dementia, aging, and ischemic brain tissues [41][42][43][44][45]. Furthermore, recent evidence in post-mortem analyses of Chronic Traumatic Encephalopathy (CTE) has demonstrated trauma-induced accumulation of a morphologically distinct subset of reactive astrocytes [46]. Characteristically, these astrocytes had a beaded 'pearl on a string' degenerative morphology.…”

Section: Results: Tbi Elicits Delayed Reactive Gliosis That Is Protramentioning

confidence: 85%

Effects of advanced age upon astrocyte-specific responses to acute traumatic brain injury in mice

Early

Gorman

Eldik

et al. 2019

Preprint

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AbstractBackgroundOlder-age individuals are at the highest risk for disability from a traumatic brain injury (TBI). Astrocytes are the most numerous glia in the brain, necessary for brain function, yet there is little known about unique responses of astrocytes in the aged-brain following TBI.MethodsOur approach examined astrocytes in young adult, 4-month-old, versus aged, 18-month-old mice, at 1, 3, and 7 days post-TBI. We selected these time points to span the critical period in the transition from acute injury to presumably irreversible tissue damage and disability. Two approaches were used to define the astrocyte contribution to TBI by age interaction: 1) tissue histology and morphological phenotyping, and 2) transcriptomics on enriched astrocytes from the injured brain.ResultsAging was found to have a profound effect on the TBI-induced loss of homeostatic astrocyte function needed for maintaining water transport and edema – namely, aquaporin-4. The loss of homoeostatic responses was coupled with a progressive exacerbation of astrogliosis in the aged brain as a function of time after injury. Moreover, clasmatodendrosis, an underrecognized astrogliopathy, was found to be significantly increased in the aged brain, but not in the young brain. As a function of TBI, we observed a transitory refraction in the number of these astrocytes, which rebounded by 7 days post-injury in the aged brain. The transcriptomics found disproportionate changes in genes attributed to reactive astrocytes, inflammatory response, complement pathway, and synaptic support in aged mice following TBI compared to young mice. Additionally, our data highlight that TBI did not evoke a clear alignment with previously defined “A1/A2” dichotomy of reactive astrogliosis.ConclusionsOverall, our findings point toward a progressive phenotype of aged astrocytes following TBI that we hypothesize to be maladaptive, shedding new insights into potentially modifiable astrocyte-specific mechanisms that may underlie increased fragility of the aged brain to trauma.

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“…Astrogliosis in CTE patients can be robust. 110 In addition, there are significant morphological overlaps. This includes localization of tau pathology to subpial, perivascular, and gray matter astrocytes, as with ARTAG.…”

Section: Aging-related Tau Astrogliopathymentioning

confidence: 99%

Chronic Traumatic Encephalopathy and Neuropathological Comorbidities

Stein

Crary

2020

Semin Neurol

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AbstractWith age, the presence of multiple neuropathologies in a single individual becomes increasingly common. Given that traumatic brain injury and the repetitive head impacts (RHIs) that occur in contact sports have been associated with the development of many neurodegenerative diseases, including chronic traumatic encephalopathy (CTE), Alzheimer's disease, Lewy body disease, and amyotrophic lateral sclerosis, it is becoming critical to understand the relationship and interactions between these pathologies. In fact, comorbid pathology is common in CTE and likely influenced by both age and the severity and type of exposure to RHI as well as underlying genetic predisposition. Here, we review the major comorbid pathologies seen with CTE and in former contact sports athletes and discuss what is known about the associations between RHI, age, and the development of neuropathologies. In addition, we examine the distinction between CTE and age-related pathology including primary age-related tauopathy and age-related tau astrogliopathy.

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Astrocytic degeneration in chronic traumatic encephalopathy

Cited by 55 publications

References 68 publications

Effects of advanced age upon astrocyte-specific responses to acute traumatic brain injury in mice

Effects of advanced age upon astrocyte-specific responses to acute traumatic brain injury in mice

Effects of advanced age upon astrocyte-specific responses to acute traumatic brain injury in mice

Chronic Traumatic Encephalopathy and Neuropathological Comorbidities

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