This study examined the role that pre-injury alcohol and marijuana use have on the incidence of post-traumatic seizures, as well as their relationship with their known risk factors. We hypothesized that pre-injury alcohol and marijuana use would independently predict post-traumatic seizures at 3 separate time points, categorized as immediate, early, and both immediate and early seizures. 3,875 participants were identified using the Traumatic Brain Injury Model Systems National Database. The primary outcome was the occurrence of a post-traumatic seizure. The primary exposure variables of interest included pre-injury alcohol and marijuana use. Covariates included presence of pre-injury seizures, age and sex at injury, and injury-related characteristics. The relationship between pre-injury alcohol and marijuana use, and each seizure outcome was examined using separate logistic regression models, with results reported as odds ratios with 95% confidence intervals. From the total number of participants 88.8% did not experience seizures, with immediate seizures observed in 269 participants, early seizures observed in 111 participants, and both immediate and early seizures observed in 53 participants. For the immediate seizure group pre-injury alcohol use was not significantly associated with immediate seizures. In the early seizure group, however, alcohol use in the month prior to injury was significantly associated with increased odds, while pre-injury marijuana use was associated with decreased odds. In the combined immediate and early group, alcohol use was not significantly associated, but pre-injury marijuana use was associated with an increased odds of seizure. This study illustrated a possible priming effect of pre-injury alcohol use on post-injury brains, showing a stronger association between the development of early compared to immediate seizures. The effect of marijuana on seizure risk was less clear, nevertheless reinforcing the importance of strong counseling for this vulnerable population, particularly for those with a pre-morbid history of alcohol/substance use.
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in Low- and Middle-Income Countries (LMICs). Prior clinical trials suggest early tranexamic acid (TXA) may reduce mortality, with effects varying by TBI severity; however, evidence in LMICs remains limited. TBI patients (Abbreviated Injury Scale (AIS) Head Severity ≥2) in Western Cape, South Africa who presented within 3 hours of injury were included. Severe hemorrhage, significant non-head injuries (AIS Body ≥3), or receipt of blood products or TXA after 3 hours were excluded. TXA within 3 hours defined treatment, whereas controls did not receive TXA. An adjusted analysis on 7-day mortality (primary outcome) as well as at 72-hours, 30 days, and discharge neurologic status was performed. Subgroup analyses evaluated injury type, TBI severity, TXA timing, and dose. 1794 patients were included, 144 (8%) received TXA. After adjustment, TXA administration was associated with lower odds of 72-hour mortality (marginal odds ratio [mOR] =0.75, 95% confidence interval [CI] 0.44-1.26) and 7-day mortality (mOR=0.75, 95% CI 0.43-1.32), although not significant. Patients with severe TBI (GCS <8) had lower 72-hour odds of mortality (mOR=0.54, 95% CI 0.31-0.94) and 7-day (mOR=0.47, 95% CI 0.26-0.83). Subgroup and sensitivity analyses demonstrated no significant differences in 7-day mortality by injury type, TXA timing, or dose. TXA was associated with significantly lower 72-hour and 7-day mortality in severe TBI, and statistically nonsignificant large reductions in mortality in the general cohort. Our findings add to the limited evidence that TXA may benefit patients with severe TBI in resource-limited settings.
Traumatic brain injury (TBI) often results in acute and chronic deficits that can have profound effects on the affected individual and their families. While TBI is known to trigger widespread transcriptome changes, concurrent evaluation of the influence of sex on these changes has been understudied. To explore transcriptomic-wide responses between sexes after TBI, we administered a moderate-to-severe cortical contusion injury (CCI) or sham surgery to groups of adult male and female C57BL/6 mice. Animals were euthanized 5 days post-injury, the ipsilateral hippocampi were quickly dissected, and total RNA was isolated and sequenced. Differentially expressed genes (DEGs) were identified across all groups using a single factorial analysis and the results used for gene ontology enrichment analysis to gain a high-level overview of differences and similarities in the transcriptomic response to CCI. Both male and female mice exhibited widespread significant changes in gene expression 5 days after injury (│log 2 -fold change│>0.5, adjusted p-value <0.05). Adult male mice had 3902 genes with significantly altered expression in the hippocampus 5 days post-CCI (3238 downregulated and 664 upregulated) while 899 genes (114 downregulated, 785 upregulated) were altered in females. Gene ontology (GO) analysis of DEGs showed a prominent enrichment for upregulated immune and inflammatory-related biological process terms in both females and males. Genes exhibiting downregulated expression in male mice were associated with dendritic development and synaptic reorganization GO terms while the downregulated female transcriptomic response was not significantly enriched for any terms. Although many of the same GO terms were altered in both sexes, the specific genes within these terms were often unique suggesting that similar biological responses may be achieved through different means in each sex. This work highlights the need for continued studies in which sex as a biological variable is considered in the development of therapeutic strategies for TBI.
Falls are the leading cause of injury-related morbidity and mortality among older adults, particularly in long-term care (LTC) facilities. Although head impacts are common during falls, the relationship between impact occurrence, injury characteristics, and hospital transport remains inadequately defined. The objectives of this study were to (1) compare falls with and without head impact, (2) quantify unrecognized head impacts and their contexts, (3) examine factors associated with head injury occurrence, and (4) identify predictors of hospital transport following head impacts. This secondary analysis used an open-source video dataset from two LTC facilities. Three raters reviewed each of the 300 fall videos to determine the presence of head impact. Transport and injury data were extracted directly from the open-source, observational video dataset. Falls were characterized using the Fall Video Analysis Questionnaire. Generalized estimating equations evaluated predictors of head injury, and logistic regression modeled predictors of hospital transport. Head impacts were common yet often underrecognized when relying on reported or visible injuries. Many falls without documented head injury demonstrated clear head impact on video, indicating that visible injury is a poor proxy for impact. Hospital transport following head impact was uncommon and was primarily associated with visible injuries rather than patient characteristics or fall history. Most head impacts, including those without obvious injury, did not result in transport. These findings suggest that reliance on external injury may lead to underrecognition and potential under-triage of head trauma. Improved detection strategies beyond visible injury are needed to better identify clinically significant head impacts.
After spinal cord injury (SCI), various cells including oligodendrocyte precursors, astrocytes and macrophages proliferate. Their damage may induce apoptosis or cellular senescence that is mediated and maintained by upregulation of the cell cycle inhibitors p21/CDKN1A or p16/CDKN2A. If persistent, cellular senescence promotes chronic inflammation and fibrosis. Therefore, expression of cellular senescence markers was evaluated following a moderate T9 contusive SCI in mice. Meta-analysis of contused spinal cord transcriptomes revealed an overrepresentation of senescence-related transcripts. The highest enrichment occurred two days after SCI and gradually declined at later times. The p21/Cdkn1a transcript peaked at two days post-injury and remained elevated for up to 60 days. Conversely, p16/Cdkn2a , was unaffected and showed very low expression. Interestingly, p21 protein levels increased exclusively at three days post-SCI. Nuclear p21 immunofluorescence signal was observed in the injury core and bordering spared tissues where majority of positive cells resided. In the latter region, 80% p21-positive cells co-stained with the oligodendrocyte lineage cell marker SOX10 or the astrocyte marker GFAP while 10% co-stained with the microglia/macrophage marker IBA1. These findings suggest that p21 upregulation represents a transient response to SCI that may involve regulated translation and/or protein degradation. In the contused spinal cord, p21 may contribute to the initial stages of scar formation including negative regulation of proliferation to protect glia from DNA damage. While p21-expressing cells do not appear to persist after SCI, a chronic cellular senescence response induced or maintained independently of p21 cannot be ruled out.
