Sex Differences in Animal Models of Traumatic Brain Injury

Rubin, Todd G.; Lipton, Michael L.

doi:10.1177/1179069519844020

Cited by 78 publications

(51 citation statements)

References 98 publications

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“…Immune response to injury in the brain is a key mediator in recovery, and progressive impairments become apparent when compromised (20,87). Many groups have reported activation of neuroinflammatory response after TBI, which is also recognized as a key player in recovery (88,89) but very few studies have reported sex divergence of TBI-mediated neuroinflammation. In humans, gender-differences in immunity are well-established (90,91) as seen from the fact that females produce more severe immune reactions and have a higher incidence of autoimmune diseases, which may result from the influence of sex hormones on the immune system (92).…”

Section: Drosophila Males Show Weaker Immune Response After Tbimentioning

confidence: 99%

Drosophila Exhibit Divergent Sex-Based Responses in Transcription and Motor Function After Traumatic Brain Injury

2020

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Every year, millions of people in the US suffer brain damage from mild to severe traumatic brain injuries (TBI) that result from a sudden impact to the head. Despite TBI being a leading cause of death and disability worldwide, sex differences that contribute to varied outcomes post-injury are not extensively studied and therefore, poorly understood. In this study, we aimed to explore biological sex as a variable influencing response to TBI using Drosophila melanogaster as a model, since flies have been shown to exhibit symptoms commonly seen in other mammalian models of TBI. After inflicting TBI using the high-impact trauma device, we isolated w 1118 fly brains and assessed gene transcription changes in male and female flies at control and 1, 2, and 4 hr after TBI. Our results suggest that overall, Drosophila females show more gene transcript changes than males. Females also exhibit upregulated expression changes in immune response and mitochondrial genes across all time-points. In addition, we looked at the impact of injury on mitochondrial health and motor function in both sexes before and after injury. Although both sexes report similar changes in mitochondrial oxidation and negative geotaxis, locomotor activity appears to be more impaired in males than females. These data suggest that sex-differences not only influence the response to TBI but also contribute to varied outcomes post-injury.

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Section: Drosophila Males Show Weaker Immune Response After Tbimentioning

confidence: 99%

Drosophila Exhibit Divergent Sex-Based Responses in Transcription and Motor Function After Traumatic Brain Injury

2020

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“…It is important to highlight that this study uses only male rats and it may limit the translation of our findings into the clinic (Rubin and Lipton, 2019). Therefore, future preclinical studies are needed to assess the effect of sex on mTBI outcomes.…”

Section: Technical Limitations and Future Directionsmentioning

confidence: 99%

In VivoDiffusion Tensor Imaging in Acute and Subacute Phases of Mild Traumatic Brain Injury in Rats

Molina

Salo

Abdollahzadeh

et al. 2020

eNeuro

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Mild traumatic brain injury (mTBI) is the most common form of TBI with 10-25% of the patients experiencing long-lasting symptoms. The potential of diffusion tensor imaging (DTI) for evaluating microstructural damage Significance Statement Mild traumatic brain injury (mTBI) is a major health problem worldwide with an unclear diagnosis. Using the lateral fluid percussion (LFP) injury model in rats, we induced mTBI to assess the potential of in vivo diffusion tensor imaging (DTI) for non-invasively detecting progressive microstructural tissue damage. To interpret the changes observed in DTI, we performed extensive quantitative histologic assessment of the tissue microstructure. From the acute to subacute phases after mTBI, in vivo DTI detected progressive microstructural tissue alterations in the white and gray matter associated with axonal damage and gliosis. Although in vivo DTI failed to detect secondary tissue damage far from the primary lesion, these findings provide new insights for detecting mild tissue damage using in vivo DTI.

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“…A contribution from anesthetics is suggested by a report of lower mortality after TBI in awake compared to anesthetized animals [50]. The higher ratio of female mice dying from multifactorial injury might be attributed to sexspecific factors, as multiple studies show that while men are more likely to sustain a TBI, women are at greater risk for poor outcomes [45]. Furthermore, a recent finding in rats reported sexual dimorphism, with females displaying a prolonged state of cephalic hyperalgesia [8].…”

Section: Choice Of Tbi Modelsmentioning

confidence: 99%

Multifactorial and closed head impact traumatic brain injuries cause distinct tactile hypersensitivity profiles

Wattiez

Castonguay

Gaul

et al. 2020

Preprint

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Chronic complications of traumatic brain injury (TBI) represent one of the greatest financial burdens and sources of suffering in society today. A substantial number of these patients suffer from post-traumatic headache (PTH), which is typically associated with tactile allodynia.Unfortunately, this phenomenon has been under-studied, in large part due to the lack of wellcharacterized laboratory animal models. We have addressed this gap in the field by characterizing the tactile sensory profile of two non-penetrating models of PTH. We show that multifactorial TBI, consisting of aspects of impact, acceleration/deceleration, and blast wave exposure, produces long term tactile hypersensitivity and central sensitization, phenotypes reminiscent of PTH in patients, in both cephalic and extracephalic regions. By contrast, closed head injury induces only transient cephalic tactile hypersensitivity, with no extracephalic consequences. Both models show more severe phenotype with repetitive daily injury for three days, compared to either one or three successive injuries in a single day, providing new insight into patterns of injury that may place patients at greater risk of developing PTH. Importantly, even after recovery from transient cephalic tactile hypersensitivity, mice subjected to closed head injury had persistent hypersensitivity to established migraine triggers, including calcitonin gene-related peptide (CGRP) and sodium nitroprusside, a nitric oxide donor. Our results offer new tools for studying PTH, as well as preclinical support for a pathophysiologic role of CGRP in this condition. SummaryTwo models of post-traumatic headache after traumatic brain injury provide novel laboratory tools and insights in relative risks of injury and therapeutic opportunities.

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Sex Differences in Animal Models of Traumatic Brain Injury

Cited by 78 publications

References 98 publications

Drosophila Exhibit Divergent Sex-Based Responses in Transcription and Motor Function After Traumatic Brain Injury

Drosophila Exhibit Divergent Sex-Based Responses in Transcription and Motor Function After Traumatic Brain Injury

In VivoDiffusion Tensor Imaging in Acute and Subacute Phases of Mild Traumatic Brain Injury in Rats

Multifactorial and closed head impact traumatic brain injuries cause distinct tactile hypersensitivity profiles

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