Gender impacts mortality after traumatic brain injury in teenagers

Ley, Eric J.; Short, Scott S.; Liou, Douglas Z.; Singer, Matthew M.; Mirocha, James; Melo, Natália; Bukur, Marko; Salim, Ali

doi:10.1097/ta.0b013e31829d024f

Cited by 57 publications

(57 citation statements)

References 14 publications

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“…A recent retrospective mortality study of TBI, involving more than 20,200 prepubescent and pubescent patients with moderate-to-severe TBI, showed that mortality rates were significantly lower in the prepubescent patients than in pubescent patients ( p < 0.0001) (6). Within the pubescent group, it was further found that females had a significantly lower mortality rate than males.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent retrospective mortality study, involving 10,135 prepubescent (0–12 years), and 10,145 pubescent (12–18 years) hospitalized patients who sustained isolated moderate-to-severe TBI (defined as a head Abbreviated Injury Scale (AIS) score of 3 or greater). Ley et al (6) found a significantly reduced mortality rate in prepubescent patients than in pubescent patients (5.2 vs. 8.6%, p < 0.0001). Additionally, females in the pubescent but not in the prepubescent age group showed a significantly greater decrease in mortality than males.…”

Section: Introductionmentioning

confidence: 95%

“…Adolescent animals were studied because they are more sensitive to stress than adult, a trait that could have a significant influence on disease development in adulthood (57–60). Furthermore, a gender difference in TBI outcome has been shown for pubescent animals, but not for prepubescent ones (6). …”

Section: Introductionmentioning

confidence: 99%

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Differential Expression of Brain Cannabinoid Receptors between Repeatedly Stressed Males and Females may Play a Role in Age and Gender-Related Difference in Traumatic Brain Injury: Implications from Animal Studies

et al. 2014

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Inconsistent gender differences in the outcome ofTBI have been reported.The mechanism is unknown. In a recent male animal study, repeated stress followed by TBI had synergistic effects on brain gene expression and caused greater behavioral deficits. Because females are more likely to develop anxiety after stress and because anxiety is mediated by cannabinoid receptors (CBRs) (CB 1 and CB 2 ), there is a need to compare CB 1 and CB 2 expression in stressed males and females. CB 1 and CB 2 mRNA expression was determined in the amygdala, hippocampus, prefrontal cortex (PFC), and hypothalamus of adolescent male and female rats after 3 days of repeated tail-shock stress using qPCR. PFC CB 1 and CB 2 protein levels were determined using Western blot techniques. Both gender and stress had significant effects on brain CB 1 mRNA expression levels. Overall, females showed significantly higher CB 1 and CB 2 mRNA levels in all brain regions than males (p < 0.01). Repeated stress reduced CB 1 mRNA levels in the amygdala, hippocampus, and PFC (p < 0.01, each). A gender × stress interaction was found in CB 1 mRNA level in the hippocampus (p < 0.05), hypothalamus (p < 0.01), and PFC (p < 0.01). Within-sex one-way ANOVA analysis showed decreased CB 1 mRNA in the hippocampus, hypothalamus, and PFC of stressed females (p < 0.01, each) but increased CB 1 mRNA levels in the hypothalamus of stressed males (p < 01).There was a gender and stress interaction in prefrontal CB 1 receptor protein levels (p < 0.05), which were decreased in stressed females only (p < 0.05). Prefrontal CB 2 protein levels were decreased in both male and female animals after repeated stress (p < 0.05, each). High basal levels of CBR expression in young naïve females could protect against TBI damage whereas stress-induced CBR deficits could predict a poor outcome of TBI in repeatedly stressed females. Further animal studies could help evaluate this possibility.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

Differential Expression of Brain Cannabinoid Receptors between Repeatedly Stressed Males and Females may Play a Role in Age and Gender-Related Difference in Traumatic Brain Injury: Implications from Animal Studies

et al. 2014

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“…In humans, epidemiological studies showed more contradictory results on genderassociated morbidity. Female gender correlated with reduced mortality and complication rates after TBI in some studies [15,9,2], while other studies found no gender association [33,14] or even higher mortality in in females [7,29].…”

Section: Introductionmentioning

confidence: 94%

COX-2 regulation and TUNEL-positive cell death differ between genders in the secondary inflammatory response following experimental penetrating focal brain injury in rats

et al. 2015

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COX-2 regulation differed between genders after TBI. The increased COX-2 expression in male rats correlated with increased apoptotic cell death detected by increased TUNEL staining at 24 h, but not with neuronal necrosis measured by Flouro-Jade. Astrogliosis and microgliosis did not differ, confirming a comparable level of trauma. The gender-specific trait of the secondary inflammatory response may be connected to prostaglandin regulation, which may partially explain gender variances in outcome after TBI.

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“…Tailoring therapeutic interventions to our patients’ characteristics, most notably gender, could improve outcomes after TBI. Indeed we have growing evidence that gender and hormonal influences affect outcomes after TBI (10) and alter responses to vasopressors after brain injury (11). …”

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confidence: 99%