Search

Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.

Traumatic brain injury causes widespread neurological lesions that can be reproduced in animals with the lateral fluid percussion (LFP) model. The characterization of the pattern of neuronal death generated in this model remains unclear, involving both cortical and subcortical brain regions. Here, 7 days after moderate (3 atmospheres absolute [ATA]) or severe (3.8 ATA) LFP, we estimated neuronal loss by using immunohistochemistry together with a computer-assisted automated method for quantifying neuronal density in brain sections. Neuronal counts were performed ipsilateral to the impact, in the parietal cortex ventral to the site of percussion, in the temporal cortex, in the dorsal thalamus, and in the hippocampus. These results were compared with the counts observed at similar areas in sham animals. We found that neuronal density was severely decreased in the temporal cortex (-60%), in the dorsal thalamus (-63%), and in area CA3 of the hippocampus (-36%) of injured animals compared with controls but was not significantly modified in the cortices located immediately ventral to the impact. Total cellular density increased in brain structures displaying neuronal death, suggesting the presence of gliosis. The increase in the severity of LFP did not change the pattern of neuronal injury. This automated method simplified the study of neuronal loss following traumatic brain injury and allowed the identification of a pattern of neuronal loss that spreads from the dorsal thalamus to the temporal cortex, with the most severe lesions being in brain structures remote from the site of impact., (© 2015 Wiley Periodicals, Inc.)

This study sought to determine the bio-availability of recombinant human erythropoietin (EPO) in the brain and blood and its effects on the cerebral concentrations of the inflammatory mediators interleukin-1beta (IL-1beta) and macrophage-inflammation protein-2 (MIP-2) following lateral fluid percussion brain injury (FPI) in the rat. After induction of moderate FPI (1.6-1.8 atm), EPO was injected intraperitoneally (IP) or intravenously (IV) at doses of 1000-5000 U/kg in a randomized and blinded manner. Animals were then sacrificed at time points (4, 8, 12, 24 h) post-trauma, and the brain concentrations of EPO, IL-1beta, and MIP-2 were determined. EPO administration leads to a dose-dependent increase in the brain concentration of the drug; however, this could only be detected at doses of 3000 and 5000 U/kg. The cerebral concentration peaked in the first 4 h following trauma. EPO concentrations were significantly higher and decreased more slowly in the traumatized cortex compared to the contralateral side (p<0.0125). IV EPO (5000 U/kg) produced slightly higher concentrations of EPO than same doses injected IP; however, this was not significant. At a dose of 5000 U/kg, EPO significantly reduced the increase in IL-1beta at 8 and 12 h in both cortical sides. It also reduced the increase in MIP-2 but only after 8 h, on the contralateral side and after 12 h on the ipsilateral side. Our results suggest that EPO crosses the blood-brain barrier (BBB) by 4 h after trauma and is localized primarily in the traumatized cortex. Further, it has biological efficacy at 8 h on several inflammatory proteins, yet must be employed at high doses to cross the BBB.

Background: Thoracic trauma is a major cause of death in trauma patients and road traffic accident (RTA)-related thoracic injuries have different characteristics than those with non-RTA related thoracic traumas, but this have been poorly described. The main objective was to investigate the epidemiology, injury pattern and outcome of patients suffering a significant RTA-related thoracic injury. Secondary objective was to investigate the influence of serious thoracic injuries on mortality, compared to other serious injuries. Methods: We performed a multicenter observational study including patients of the Rhône RTA registry between 1997 and 2016 sustaining a moderate to lethal (Abbreviated Injury Scale, AIS≥2) injury in any body region. A subgroup (AISThorax≥2 group) included those with one or more AIS≥2 thoracic injury. Descriptive statistics were performed for the main outcome and a multivariate logistic regression was computed for our secondary outcome. Results: A total of 176,346 patients were included in the registry and 6,382 (3.6%) sustained a thoracic injury. Among those, median age [IQR] was 41 [25–58] years, and 68.9% were male. The highest incidence of thoracic injuries in female patients was in the 70–79 years age group, while this was observed in the 20–29 years age group among males. Most patients were car occupants (52.3%). Chest wall injuries were the most frequent thoracic injuries (62.1%), 52.4% of which were multiple rib fractures. Trauma brain injuries (TBI) were the most frequent concomitant injuries (29.1%). The frequency of MAISThorax = 2 injuries increased with age while that of MAISThorax = 3 injuries decreased. A total of 16.2% patients died. Serious (AIS≥3) thoracic injuries (OR = 12.4, 95%CI [8.6;18.0]) were strongly associated with mortality but less than were TBI (OR = 27.9, 95%CI [21.3;36.7]). Conclusion: Moderate to lethal RTA-related thoracic injuries were rare. Multiple ribs fractures, pulmonary contusions, and sternal fractures were the most frequent anatomical injuries. The incidence, injury pattern and mechanisms greatly vary across age groups. [ABSTRACT FROM AUTHOR]

Background: Since 2002, France has been strengthening legislation on road traffic. This study is intended to evaluate the changes in Traumatic Brain Injury (TBI) incidence and mortality resulting from Road Traffic Collision (RTC) in the two 6-year periods before and after 2002. Methods: We used a Registry of all RTC casualties in the Rhône Department of France. Each casualty was coded according to the Abbreviated Injury Scale (AIS). The study describes changes in demographic variables, TBI (AIS ≥ 2) incidence and mortality, other body lesions (AIS ≥ 3) associated with TBI, road user types, seatbelt and helmet wearing. Findings: RTC casualty occurrences decreased by 21% (from 64,312 to 50,746) during the period after 2002. TBI occurrence accounted for 8.6% and 6.7% of all RTC in both periods. This corresponds to a reduction of TBI casualty incidence (-42%), which was much more pronounced than RTC casualty incidence (-25%) (p < 0.0001). Severe and critical TBI (AIS-4 and -5) incidences were reduced by half as much (-21%), compared to TBI incidence. TBI mortality rate (among population) and lethality (among TBI related to RTC casualties) decreased 56% and 23%, respectively. This reduction particularly affected car occupants and victims who deceased. TBI incidence decreased 43% in all 10-year age classes until 60 on average, this decrease declining with age in the period after 2002. After adjustment for age, sex, road user types, and severity of lesions at the head and other body regions, logistic regression analysis displayed a protective effect of the period following 2002, on the risk of death after RTC-related TBI. Interpretation: The greater reductions in the incidence, severity and mortality of TBI when compared with the reduction of casualty incidence have mainly affected car users. These results should be attributable to the improvements in standards of care, primary safety of the car fleet and general road architecture safety. However, the increased reduction in the TBI epidemics in France, when compared to those observed in other developed countries for the same periods, suggests that the effects should be strongly attributable to changes in road user behaviour induced by law enforcement. The at-risk groups for TBI after RTC are now two-wheel users (motorized or not) and individuals over 60 years of age. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is common in both military and civilian populations, and often results in neurobehavioral sequelae that impair quality of life in both patients and their families. Although individuals who are chronically exposed to stress are more likely to experience TBI, it is still unknown whether pre-injury stress influences the outcome after TBI. The present study tested whether behavioral and cognitive long-term outcome after TBI in rats is affected by prior exposure to an innate stress stimulus. Young adult male Sprague-Dawley rats were exposed to the predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) or to water (WAT); exposure was repeated eight times at irregular intervals over a 2-week period. Rats were subsequently subjected to either mild-to-moderate bilateral brain injury (lateral fluid percussion [LFP]) or sham surgery (Sham). Four experimental groups were studied: Sham-WAT, Sham-TMT, LFP-WAT and LFP-TMT. Compared with Sham-WAT rats, LFP-WAT rats exhibited transient locomotor hyperactivity without signs of anxiety, minor spatial learning acquisition and hippocampal long-term potentiation deficits, and lower baseline activity of the hypothalamic-pituitary-adrenal axis with slightly stronger reactivity to restraint stress. Exposure to TMT had only negligible effects on Sham rats, whereas it exacerbated all deficits in LFP rats except for locomotor hyperactivity. Early brain inflammatory response (8 h post-trauma) was aggravated in rats pre-exposed to TMT, suggesting that increased brain inflammation may sustain functional deficits in these rats. Hence, these data suggest that pre-exposure to stressful conditions can aggravate long-term deficits induced by TBI, leading to severe stress response deficits, possibly due to dysregulated inflammatory response. [ABSTRACT FROM AUTHOR]

The influence that recurrent stress exposure before injury exerts on outcome after traumatic brain injury (TBI) has been little studied, although prevalence of TBI is high in both civilian and military populations repeatedly exposed to life-threatening stressful situations. Here, using a rat model, we aimed at determining if early post-TBI modulation of the expression of brain-derived neurotrophic factor (BDNF) and of its high-affinity receptor TrkB, which are known to promote neuroprotection after brain injury, is influenced by preexposure to life-threatening stress. Adult male Sprague-Dawley rats were repeatedly exposed to predator odor 2-4-5-trimethyl-3-thiazoline (TMT), which elicits fear response in rodents, or were exposed to water instead of TMT for 2 weeks, and then were subjected to either bilateral mild-to-moderate fluid percussion brain injury (LFP) or Sham surgery. We measured the expression of BDNF and TrkB at 8 hours post-TBI/surgery in the neocortex, hippocampus and ventral limbic region (VLR) using RT-qPCR. The most robust alteration of BDNF expression compared to Sham condition was observed when rats were pre-exposed to TMT before LFP, although it was not specific to a given brain area. TMT, LFP and combination of both all influenced TrkB expression with regional specificities. Overall, TBI alone had weak effects on TrkB expression, contrasting with the significant alterations induced by TMT exposure alone. The combination of TMT exposure and LFP produced effects similarly to stress alone. Thus, the reactivity of TrkB expression to LFP alone was different from that triggered by the TMT-LFP combination. Hence, these data suggest that repeated pre-exposure to life-threatening stimulus modifies the reactivity of the BDNF-TrkB system, and may therefore influence outcome after TBI. [ABSTRACT FROM AUTHOR]