Criteria to define mild, moderate, and severe traumatic brain injury in the mouse controlled cortical impact model

Siebold, Lorraine; Obenaus, André; Goyal, Ravi

doi:10.1016/j.expneurol.2018.07.004

Cited by 92 publications

(88 citation statements)

References 97 publications

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“…The controlled cortical impact (CCI) injury was reproduced using the Leica electromagnetic impactor and a 3.0-mm convex tip, as we have previously described [30,33,34]. Impact parameters were as follows: impact velocity of 4.0 m/s, dwell time of 0.3 s, to a depth of − 0.9 mm, and rotated 20°on the vertical axis to match the curvature of the brain, resulting in an impact force of 0.028 N. These impact parameters align with previously suggested guidelines for CCI injury severity to be classified as mild to moderate in severity [35]. Following surgery, scalps were closed using surgical staples, and mice were transferred to a recovery cage placed on top of a heating pad.…”

Section: Surgical Proceduressupporting

confidence: 61%

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: Surgical Proceduressupporting

confidence: 61%

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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“…Evidence for the deleterious effects of CTLs in TBI comes from our findings in which mice that are genetically deficient or pharmacologically depleted of CD8 + T cells had improved neurological outcomes and reduced myelin pathology in the spinal cord over 8 weeks. While no evidence of improved cognition was found in CD8 + T cell-depleted mice, it is possible that cognitive changes may have occurred earlier (Siebold et al, 2018). In experimental stroke, mice displayed improved behavioral function and decreased neuronal loss following the depletion of CD8 + T cells, albeit within a much shorter time frame (7-14 days) (Mracsko et al, 2014).…”

Section: Discussionmentioning

confidence: 94%

Activated CD8+ T Cells Cause Long-Term Neurological Impairment after Traumatic Brain Injury in Mice

et al. 2019

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“…The controlled cortical impact (CCI) was chosen to establish the animal model of TBI as described previously [31,32]. After intraperitoneal injection of pentobarbital, a 5 mm diameter hole was drilled over the right hemisphere bone equidistant between the lambda and bregma.…”

Section: Animal Model Of Controlled Cortical Injurymentioning

confidence: 99%

Epitranscriptomic profiling of N6-methyladenosine-related RNA methylation in rat cerebral cortex following traumatic brain injury

Zhang

et al. 2020

Mol Brain

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Background: N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification of eukaryotic mRNA. It has been reported that there is a stimulus-dependent regulation of m6A in the mammalian central nervous system in response to sensory experience, learning, and injury. The mRNA m6A methylation pattern in rat cortex after traumatic brain injury (TBI) has not been investigated. Results: In this study, we conducted a genome-wide profiling of mRNA m6A methylation in rat cortex via methylated RNA immunoprecipitation sequencing (MeRIP-Seq). After TBI, the expressions of METTL14 and FTO were significantly down-regulated in rat cerebral cortex. Using MeRIP-Seq, we identified a total of 2165 significantly changed peaks, of which 1062 were significantly up-regulated and 1103 peaks were significantly down-regulated. These m6A peaks were located across 1850 genes. The analysis of both m6A peaks and mRNA expression revealed that there were 175 mRNA significantly altered methylation and expression levels after TBI. Moreover, it was found that functional FTO is necessary to repair neurological damage caused by TBI but has no effect on the spatial learning and memory abilities of TBI rats by using FTO inhibitor FB23-2.Conclusion: This study explored the m6A methylation pattern of mRNA after TBI in rat cortex and identified FTO as possible intervention targets in the epigenetic modification of TBI.

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Criteria to define mild, moderate, and severe traumatic brain injury in the mouse controlled cortical impact model

Cited by 92 publications

References 97 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

Activated CD8+ T Cells Cause Long-Term Neurological Impairment after Traumatic Brain Injury in Mice

Epitranscriptomic profiling of N6-methyladenosine-related RNA methylation in rat cerebral cortex following traumatic brain injury

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