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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]

Delayed cerebral ischemia (DCI) is a devastating complication of aneurysmal subarachnoid hemorrhage (ASAH) causing brain infarction and disability. Cerebral microdialysis (CMD) monitoring is a focal technique that may detect DCI-related neurochemical changes as an advance warning. We conducted retrospective analyses from 44 poor-grade ASAH patients and analyzed glucose, lactate, pyruvate, and glutamate concentrations in control patients without DCI (n = 19), and in patients with DCI whose CMD probe was located within (n = 17) or outside (n = 8) a new infarct. When monitored from within a lesion, DCI was preceded by a decrease in glucose and a surge in glutamate, accompanied by increases in lactate/pyruvate and lactate/glucose ratios whereas these parameters remained stable in control patients. When CMD monitoring was performed outside the lesion, the glutamate surge was absent, but glucose and L/G ratio were still significantly altered. Overall, glucose and L/G ratio were significant biomarkers of DCI (se96.0, spe73.7-68.4). Glucose and L/G predicted DCI 67 h before CT detection of a new infarct. The pathogenesis of DCI therefore induces early metabolic disturbances that can be detected by CMD as an advance warning. Glucose and L/G could provide a trigger for initiating further examination or therapy, earlier than when guided by other monitoring techniques. [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]

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]

Cardiac, ventilatory and kidney management in the critical care setting has been optimized over the past decades. Cognition and sedation represent one of the last remaning challenges. As conventional sedation is suboptimal and as the sedation evoked by alpha-2 adrenergic agonists ("cooperative" sedation with dexmedetomidine, clonidine or guanfacine) represents a valuable alternative, this manuscript covers three practical topics for which evidence-based medicine is lacking: a) Switching from conventional to cooperative sedation ("switching"): the short answer is the abrupt withdrawal of conventional sedation, immediate implementation of alpha-2 agonist infusion and the use of "rescue sedation" (midazolam bolus[es]) or "breakthrough sedation" (haloperidol bolus[es]) to stabilize cooperative sedation. b) Switching from conventional to cooperative sedation in unstable patients (e.g., refractory delirium tremens, septic shock, acute respiratory distress syndrome, etc.): to avoid hypotension and bradycardia evoked by sympathetic deactivation, the short answer is to maintain the stroke volume through volume loading, vasopressors and inotropes. c) To avoid these switches and associated difficulties, alpha-2 agonists should be considered first-line sedatives. The short answer is to administer alpha-2 agonists slowly from admission or endotracheal intubation up to stabilized cooperative sedation. The "take home" message is as follows: a) alpha-2 agonists are jointly sympathetic deactivators and sedative agents; b) sympathetic deactivation implies maintaining the stroke volume and iterative assessment of volemia. Evidence-based medicine should document our propositions. [ABSTRACT FROM AUTHOR]

Cerebral microdialysis could be useful to detect delayed cerebral ischemia in aneurysmal subarachnoid haemorrhage patients. The optimal location of the probes, however, remains controversial. Here, we determined the vascular territories with the highest infarct risk in relation to aneurysm location to define probe implantation guidelines. These guidelines were retrospectively validated by studying the likelihood of probe to fall in a secondary infarct area, and by analysing their influence to predict patient outcome. The vascular territories with highest risk of infarction were the anterior cerebral arteries for anterior communicating artery aneurysms and the ipsilateral middle cerebral artery for internal carotid artery, posterior communicating artery and middle cerebral artery aneurysms. When cerebral microdialysis probes had been implanted in these territories, 79% were located within an infarcted area versus 54% when they were implanted in other territories. Delayed cerebral ischemia was detected only when the probe was located within a brain area later affected by secondary infarction, which could justify the use of implantation guidelines. Moreover, individual patient outcomes could be predicted when probes were placed in the brain territories as suggested by this study. Thus, a precise probe placement algorithm can improve delayed cerebral ischemia detection sensitivity and allow for a better prediction concerning patient outcome. [ABSTRACT FROM AUTHOR]

Spreading depolarizations are waves of near-complete breakdown of neuronal transmembrane ion gradients, free energy starving, and mass depolarization. Spreading depolarizations in electrically inactive tissue are associated with poor outcome in patients with traumatic brain injury. Here, we studied changes in regional cerebral blood flow and brain oxygen (PbtO2), glucose ([Glc]b), and lactate ([Lac]b) concentrations in rats, using minimally invasive real-time sensors. Rats underwent either spreading depolarizations chemically triggered by KCl in naïve cortex in absence of traumatic brain injury or spontaneous spreading depolarizations in the traumatic penumbra after traumatic brain injury, or a cluster of spreading depolarizations triggered chemically by KCl in a remote window from which spreading depolarizations invaded penumbral tissue. Spreading depolarizations in noninjured cortex induced a hypermetabolic response characterized by a decline in [Glc]b and monophasic increases in regional cerebral blood flow, PbtO2, and [Lac]b, indicating transient hyperglycolysis. Following traumatic brain injury, spontaneous spreading depolarizations occurred, causing further decline in [Glc]b and reducing the increase in regional cerebral blood flow and biphasic responses of PbtO2 and [Lac]b, followed by prolonged decline. Recovery of PbtO2 and [Lac]b was significantly delayed in traumatized animals. Prespreading depolarization [Glc]b levels determined the metabolic response to clusters. The results suggest a compromised hypermetabolic response to spreading depolarizations and slower return to physiological conditions following traumatic brain injury-induced spreading depolarizations. [ABSTRACT FROM AUTHOR]

Microelectrode biosensors are a promising technique to probe the brain interstitial fluid and estimate the extracellular concentration of neurotransmitters like glutamate. Their selectivity is largely based on maintaining high substrate specificity for the enzymes immobilized on microelectrodes. However, the effect of enzyme immobilization on substrate specificity is poorly understood. Furthermore, the accuracy of biosensor measurements for brain biological extracts has not been reliably established in comparison with conventional analytical techniques. In this study, microelectrode biosensors were prepared using different enzyme immobilization methods, including glutaraldehyde, a conventional cross-linker, and poly(ethylene glycol) diglycidyl ether (PEGDE), a milder immobilization reagent. Glutaraldehyde, but not PEGDE, significantly decreased the apparent substrate specificity of glutamate and glucose oxidase. For glutaraldehyde prepared biosensors, detection of secondary substrates by glutamate oxidase increased, resulting in a significant overestimate of glutamate levels. This effect was not observed with PEGDE-based biosensors, and when brain microdialysates were analyzed, the levels of glutamate detected by biosensors were consistent with those detected by capillary electrophoresis. In addition, basal concentrations of glutamate detected in vivo were approximately 10-fold lower than the levels detected with glutaraldehyde-based biosensors (e.g., 1.2 μM vs 16 μM, respectively). Overall, enzyme immobilization can significantly impact substrate specificity, and PEGDE is well-suited for the preparation of stable and selective biosensors. This development questions some of the previous biosensor studies aimed at detecting glutamate in the brain and opens new possibilities for specific neurotransmitter detection. [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]