Blast-induced Traumatic Brain Injury Research Articles

Meningeal Damage and Interface Astroglial Scarring in the Rat Brain Exposed to a Laser-Induced Shock Wave(s).

In the past decade, signature clinical neuropathology of blast-induced traumatic brain injury has been under intense debate, but interface astroglial scarring (IAS) seems to be convincing. In this study, we examined whether IAS could be replicated in the rat brain exposed to a laser-induced shock wave(s) (LISW[s]), a tool that can produce a pure shock wave (primary mechanism) without dynamic pressure (tertiary mechanism). Under certain conditions, we observed astroglial scarring in the subpial glial plate (SGP), gray-white matter junctions (GM-WM), ventricular wall (VW), and regions surrounding cortical blood vessels, accurately reproducing clinical IAS. We also observed shock wave impulse-dependent meningeal damage (dural microhemorrhage) in vivo by transcranial near-infrared (NIR) reflectance imaging. Importantly, there were significant correlations between the degree of dural microhemorrhage and the extent of astroglial scarring more than 7 days post-exposure, suggesting an association of meningeal damage with astroglial scarring. The results demonstrated that the primary mechanism alone caused the IAS and meningeal damage, both of which are attributable to acoustic impedance mismatching at multi-layered tissue boundaries. The time course of glial fibrillary acidic protein (GFAP) immunoreactivity depended not only on the LISW conditions but also on the regions. In the SGP, significant increases in GFAP immunoreactivity were observed at 3 days post-exposure, whereas in the GM-WM and VW, GFAP immunoreactivity was not significantly increased before 28 days post-exposure, suggesting different pathological mechanisms. With the high-impulse single exposure or the multiple exposure (low impulse), fibrotic reaction or fibrotic scar formation was observed, in addition to astroglial scarring, in the cortical surface region. Although there are some limitations, this seems to be the first report on the shock-wave-induced IAS rodent model. The model may be useful to explore potential therapeutic approaches for IAS.

Prolidase Enzyme Activity as a Potential Biomarker for Blast-Induced Traumatic Brain Injury: A Study in a Rat Model

AbstractBlast-induced traumatic brain injury (TBI) poses a significant threat to individuals exposed to explosive events. We hypothesized that blast-induced neurotrauma is an oxidative stress to brain and hence prolidase (PD) enzyme, which is an antioxidant is recommended; its serum levels are better markers of degree of injury in the acute phase for TBI in a rat blast injury model. Results revealed that PD enzyme activity in the hippocampus showed a slight increase across high, medium, and low blast pressures, but remained lower than the sham group. However, serum PD enzyme activity levels were significantly higher in the blast-exposed groups compared to the sham group. Tau protein levels were significantly elevated in the blast-exposed groups. Longitudinal analysis demonstrated a decline in hippocampal PD activity over time, while tau protein levels progressively increased, suggesting a shift from initial oxidative stress to neurodegeneration. These findings suggest that blast injury triggers oxidative stress and subsequent neurodegenerative processes. The correlation with tau protein levels further supports the involvement of oxidative stress in neurodegeneration. In conclusion, this study provides insights into the underlying pathophysiological mechanisms of blast-induced TBI and highlights the potential utility of PD enzyme activity as a diagnostic marker.

Influence of trace elements changes in the cerebellum on the rat’s behavior in elevated plus maze in the early period of mild blast-induced traumatic brain injury

The aim of the current study was to determine whether there are changes in brain trace elements of rats with blast-induced trauma and if these changes affect behavior in the elevated plus maze. Materials and methods. The study was carried out on 126 sexually mature male Wistar and were divided into 3 groups: Experimental – exposed to a shock wave 26.4 ± 3.6 kPa (n = 42); Sham (n = 42), the animals of which were subjected to inhalation anesthesia with halothane and fixation in a horizontal position; and Intact (n = 42). Behavior was study in elevated plus maze. The duration of presence in the open and closed arms, the number of stands, the duration of grooming was recorded in all groups of rats for 3 minutes. After, the animals were euthanized with halothane, followed by removal of the brain. The cerebellum was completely separated for spectral analysis using energy dispersive X-ray fluorescence analysis (EDRFA) on the analyzer EXPERT 3 XL. Results. Results showed significant changes of cognitive activity in experimental group which are indicate functional disorders of the cerebellum in the form of maladaptation in space with subsequent inhibition of motor centers. Cu/Fe ratio was decreased in the 14th and 21st days and increased in the 28th. Cu/Zn ratio was decreased on the 14th day. Zn/Fe ratio was higher on the 14th and 28th days. The existence of correlations between changes in trace elements and behavioral disorders in experimental rats was established. Conclusions. In the early period of blast-induced traumatic brain injury, cerebellar dysfunction in the form of spatial maladaptation with subsequent depression of motor centers was observed in the experimental rats Correlation analysis showed the presence of different strengths and directions of relationships between the ratios of Cu/Fe, Cu/Zn and Zn/Fe in the cerebellum and behavioral indicators in the elevated plus maze (duration of stay in open and closed arms, grooming and vertical motor activity) of experimental rats.

Excitability of the Nociceptive System in Rats after Blast-Induced Traumatic Brain Injury

Excitability of the Nociceptive System in Rats after Blast-Induced Traumatic Brain Injury

LOCOMOTOR ACTIVITY OF RATS WITH BLAST-INDUCED TRAUMATIC BRAIN INJURY IN A COMPLEX MAZE

Aim – to investigate the peculiarities of rats with blast-induced brain injury movement in the complex maze.Material and methods. The study was carried out on 15 sexually mature Wistar rats. All animals were randomly divided into 3 groups: experimental group (n=5), which was anesthetized and exposed to an air shock wave with an overpressure of 26-36 kPa; sham group (n=5), which was only anesthetized, and intact group (n=5). The study of locomotor activity was performed using a complex maze for 5 consecutive days, starting on the 1st day after the simulation of blast-induced brain injury. The route of rat`s movement through the maze of three groups was graphically depicted and visually analyzed.Results of the study. The complex maze is considered to be complicated due to the presence of a central zone and T-shaped branches to the right and left, ending with feeders. The complication of the situation and task lead to fear with rapid adaptation of healthy rats. However, if the brain functions are impaired, the experimental animal loses its physiological ability to adapt and shows signs of anxiety. The analysis of the images of the movement paths showed that on the 1st day of training, the rats of the experimental group moved more actively, despite the fact that the animals did not yet know that food was waiting for them. They performed monotonous movements and went to the side sectors more often. On 2nd day, the experimental rats were more active and explored the maze more stereotypically than intact animals. On 3rd and 4th days, clear signs of spatial memory impairment in the experimental group were found in terms of lengthening the path to the feeder. On the 5th day, it was found that the experimental rats were still poorly oriented in the maze, with a monotonous examination of the side sectors.Conclusions. Thus, mild blast-induced traumatic brain injury leads to persistent impairment of spatial memory, as well as behavioral disorders in the form of anxiety. The rats of the experimental group demonstrated stereotypical locomotor activity, as evidenced by the examination of the lateral sectors of the complex maze. At the same time, the memory for food reinforcement was well developed and retained.

EXPLORATORY ACTIVITY OF RATS IN THE ACUTE PERIOD OF MILD BLAST-INDUCED TRAUMATIC BRAIN INJURY

The relevance of this work is related to the widespread use of explosive devices in military conflicts. More common and "invisible" is mild blast-induced brain injury. This can manifest through anxiety, emotional dysregulation, and spatial memory impairments. However, significant variability exists in modeling blast-induced traumatic brain injury and spatial memory assessment methods. This study aimed to investigate the exploratory activity of rats during the acute phase of mild blast-induced traumatic brain injury modelled by using a newly developed device.
 The study carried out on 18 sexually mature male Wistar rats weighing 220-270 g. The selected rats were divided into three groups: an experimental group (n=6), animals were modeled with blast-induced trauma by generating an air shock wave with an overpressure of 26.4±3.6 kPa, sham group (n=6), animals were subjected only to inhalation anesthesia with halothane and fixed in a horizontal position, and an intact group (n=6). The exploratory activity was recorded by the iPhoneXR camera; the route of movement through the maze of rats from three groups was graphically depicted and visually analyzed, as well as the number of entries into the "false shelters" was counted and the performance of experimental, sham and intact rats was compared. On the 1st day of the post-traumatic period, the experimental rats explored a greater number of "false shelters", by 72% (p<0.01) compared to intact animals and by 65% (p<0.05) compared to control animals. On the 3rd day, this activity was higher by 53% (p<0.05) compared to intact and by 67% (p<0.05) compared to control rats. On day 7, experimental rats explored more, by 86% (p<0.01) compared to intact rats and also by 86% (p<0.01) compared to control animals. The obtained results indicate an increase in the exploratory activity of rats in the acute period of mild blast-induced brain injury.

Changes of rat’s brain vesseles after air shock wave exposure

Mild blast-induced traumatic brain injury is common among the military, resulting in cognitive impairment, reduced socialization, which leads to disability and, as a result, a deterioration in the quality of life. It is considered that blood-brain barrier disruption and microvascular dysfunction are the key to this type of injury. The purpose of study was to study changes in brain vessels after air shock wave exposure. The study was carried out on 48 mature male Wistar rats, which were randomly divided into 2 groups: an experimental group, in which animals were subjected to inhalation anesthesia using halothane and exposed to a shock wave with an overpressure of 26.4±3.6 kPa, and a Sham group. After simulation of injury on days 1st, 3rd, 7th, 14th, and 21st, the rats were euthanized and the brain was removed and after all subjected to standard histological procedures and stained with hematoxylin and eosin. For immunohistochemical studies, as primary antibodies were used eNOS. The finished preparations were examined by light microscopy and photographed. Disorders of the cerebral vessels in experimental rats were detected from day 1st of the posttraumatic period. It was found that the blast wave led to vascular rupture, as well as increased vascular permeability with diapedesis of red blood cells and cerebral edema for up to 21st days. Focal violations of the vascular wall integrity in cortical and hippocampal hemocapillaries, venular link of the submembrane vessels; changes in the morphology of the metabolic vessels endothelium; uneven blood filling of the brain vessels were of major importance. These changes indicate that increased eNOS expression leads to dilation of cerebral vessels, which is a compensatory mechanism in response to injury to improve cerebral blood circulation. However, eNOS is not involved in vasodilation, which we observed up to 21st day post-trauma.

Exploiting Natural Language Processing to Unveil Topics and Trends of Traumatic Brain Injury Research.

Traumatic brain injury (TBI) has evolved from a topic of relative obscurity to one of widespread scientific and lay interest. The scope and focus of TBI research have shifted, and research trends have changed in response to public and scientific interest. This study has two primary goals: first, to identify the predominant themes in TBI research; and second, to delineate "hot" and "cold" areas of interest by evaluating the current popularity or decline of these topics. Hot topics may be dwarfed in absolute numbers by other, larger TBI research areas but are rapidly gaining interest. Likewise, cold topics may present opportunities for researchers to revisit unanswered questions. We utilized BERTopic, an advanced natural language processing (NLP)-based technique, to analyze TBI research articles published since 1990. This approach facilitated the identification of key topics by extracting sets of distinctive keywords representative of each article's core themes. Using these topics' probabilities, we trained linear regression models to detect trends over time, recognizing topics that were gaining (hot) or losing (cold) relevance. Additionally, we conducted a specific analysis focusing on the trends observed in TBI research in the current decade (the 2020s). Our topic modeling analysis categorized 42,422 articles into 27 distinct topics. The 10 most frequently occurring topics were: "Rehabilitation," "Molecular Mechanisms of TBI," "Concussion," "Repetitive Head Impacts," "Surgical Interventions," "Biomarkers," "Intracranial Pressure," "Posttraumatic Neurodegeneration," "Chronic Traumatic Encephalopathy," and "Blast Induced TBI," while our trend analysis indicated that the hottest topics of the current decade were "Genomics," "Sex Hormones," and "Diffusion Tensor Imaging," while the cooling topics were "Posttraumatic Sleep," "Sensory Functions," and "Hyperosmolar Therapies." This study highlights the dynamic nature of TBI research and underscores the shifting emphasis within the field. The findings from our analysis can aid in the identification of emerging topics of interest and areas where there is little new research reported. By utilizing NLP to effectively synthesize and analyze an extensive collection of TBI-related scholarly literature, we demonstrate the potential of machine learning techniques in understanding and guiding future research prospects. This approach sets the stage for similar analyses in other medical disciplines, offering profound insights and opportunities for further exploration.

Abstract 2149 Cell-specific differential gene expression analysis by snRNA-seq after repetitive weaponry-type blast-induced traumatic brain injury

Abstract 2149 Cell-specific differential gene expression analysis by snRNA-seq after repetitive weaponry-type blast-induced traumatic brain injury

MCC950 Attenuates Microglial NLRP3-Mediated Chronic Neuroinflammation and Memory Impairment in a Rat Model of Repeated Low-Level Blast Exposure.

Blast-induced traumatic brain injury is typically regarded as a signature medical concern for military personnel who are exposed to explosive devices in active combat zones. However, soldiers as well as law enforcement personnel may be repeatedly exposed to low-level blasts during training sessions with heavy weaponries as part of combat readiness. Service personnel who sustain neurotrauma from repeated low-level blast (rLLB) exposure do not display overt pathological symptoms immediately but rather develop mild symptoms including cognitive impairments, attention deficits, mood changes, irritability, and sleep disturbances over time. Recently, we developed a rat model of rLLB by applying controlled low-level blast pressures (≤ 70 kPa) repeated five times successively to mimic the pressures experienced by service members. Using this model, we assessed anxiety-like symptoms, motor coordination, and short-term memory as a function of time. We also investigated the role of the NLRP3 inflammasome, a complex involved in chronic microglial activation and pro-inflammatory cytokine interleukin (IL)-1β release, in rLLB-induced neuroinflammation. NLRP3 and caspase-1 protein expression, microglial activation, and IL-1β release were examined as factors likely contributing to these neurobehavioral changes. Animals exposed to rLLB displayed acute and chronic short-term memory impairments and chronic anxiety-like symptoms accompanied by increased microglial activation, NLRP3 expression, and IL-1β release. Treatment with MCC950, an NLRP3 inflammasome complex inhibitor, suppressed microglial activation, reduced NLRP3 expression and IL-1β release, and improved short-term memory deficits after rLLB exposure. Collectively, this study demonstrates that rLLB induces chronic neurobehavioral and neuropathological changes by increasing NLRP3 inflammasome protein expression followed by cytokine IL-1β release.

Investigating neuropathological changes and underlying neurobiological mechanisms in the early stages of primary blast-induced traumatic brain injury: Insights from a rat model

The utilization of explosives and chemicals has resulted in a rise in blast-induced traumatic brain injury (bTBI) in recent times. However, there is a dearth of diagnostic biomarkers and therapeutic targets for bTBI due to a limited understanding of biological mechanisms, particularly in the early stages. The objective of this study was to examine the early neuropathological characteristics and underlying biological mechanisms of primary bTBI. A total of 83 Sprague Dawley rats were employed, with their heads subjected to a blast shockwave of peak overpressure ranging from 172 to 421 kPa in the GI, GII, and GIII groups within a closed shock tube, while the body was shielded. Neuromotor dysfunctions, morphological changes, and neuropathological alterations were detected through modified neurologic severity scores, brain water content analysis, MRI scans, histological, TUNEL, and caspase-3 immunohistochemical staining. In addition, label-free quantitative (LFQ)-proteomics was utilized to investigate the biological mechanisms associated with the observed neuropathology. Notably, no evident damage was discernible in the GII and GI groups, whereas mild brain injury was observed in the GIII group. Neuropathological features of bTBI were characterized by morphologic changes, including neuronal injury and apoptosis, cerebral edema, and cerebrovascular injury in the shockwave's path. Subsequently, 3153 proteins were identified and quantified in the GIII group, with subsequent enriched neurological responses consistent with pathological findings. Further analysis revealed that signaling pathways such as relaxin signaling, hippo signaling, gap junction, chemokine signaling, and sphingolipid signaling, as well as hub proteins including Prkacb, Adcy5, and various G-protein subunits (Gnai2, Gnai3, Gnao1, Gnb1, Gnb2, Gnb4, and Gnb5), were closely associated with the observed neuropathology. The expression of hub proteins was confirmed via Western blotting. Accordingly, this study proposes signaling pathways and key proteins that exhibit sensitivity to brain injury and are correlated with the early pathologies of bTBI. Furthermore, it highlights the significance of G-protein subunits in bTBI pathophysiology, thereby establishing a theoretical foundation for early diagnosis and treatment strategies for primary bTBI.

The state of antioxidant system and emotional status in rats with mild blast-induced traumatic brain injury

The aim was to evaluate the markers of emotional status and the antioxidant system activity in rats with blast-induced traumatic brain injury. Materials and methods. The study carried out on 85 sexually mature male Wistar rats in compliance with the current legislation on humane treatment of animals. The selected rats were randomly divided into three groups: I – study in the Barnes maze; II – study in the Open Field test; and III – study of glutathione reductase activity in a solution of rat erythrocyte’s hemolysate. In each of these groups, three groups were formed: Experimental – exposed to a shock wave with an overpressure of 26.4 ± 3.6 kPa; the Sham – subjected only to halothane and fixation; and the Intact group. Results. Showed a disturbance in the emotional status and the oxidative stress development in rats with blast-induced trauma. The time of experimental rats freezing in the Barnes maze increased by 69 % (p < 0.01) on 28th day compared to 1st day, indicating the development of fear and negative emotionality. Changes in the defecation acts number indicate the development of anxiety in the acute period (1–3 days), followed by a depression-like state. The glutathione reductase activity in experimental rats was significantly higher compared to sham and intact rats, but gradually decreased inside in the experimental group. The results of the correlation analysis indicate the presence of weak relationships between the freezing time and the glutathione reductase activity. The positive relationship of a strong degree was found between the number of defecation acts and glutathione reductase on 1st day and a negative relationship of a strong degree was found on 7th day. Conclusions. We suppose that oxidative stress is a link, but not the leading one, in the pathogenesis of emotional disturbance in rats with blast-induced brain injury.

Predicting shock-induced cavitation using machine learning: implications for blast-injury models.

While cavitation has been suspected as a mechanism of blast-induced traumatic brain injury (bTBI) for a number of years, this phenomenon remains difficult to study due to the current inability to measure cavitation in vivo. Therefore, numerical simulations are often implemented to study cavitation in the brain and surrounding fluids after blast exposure. However, these simulations need to be validated with the results from cavitation experiments. Machine learning algorithms have not generally been applied to study blast injury or biological cavitation models. However, such algorithms have concrete measures for optimization using fewer parameters than those of finite element or fluid dynamics models. Thus, machine learning algorithms are a viable option for predicting cavitation behavior from experiments and numerical simulations. This paper compares the ability of two machine learning algorithms, k-nearest neighbor (kNN) and support vector machine (SVM), to predict shock-induced cavitation behavior. The machine learning models were trained and validated with experimental data from a three-dimensional shock tube model, and it has been shown that the algorithms could predict the number of cavitation bubbles produced at a given temperature with good accuracy. This study demonstrates the potential utility of machine learning in studying shock-induced cavitation for applications in blast injury research.

Enhanced attention in rats following blast-induced traumatic brain injury

PurposeTo evaluate visuo-cognitive sequelae following blast-induced traumatic brain injury in a rat model. MethodsRats were randomly assigned to one of four groups depending on the intensity/quantity of a blast received in a blast chamber: sham (no blast), low intensity (22 psi), medium intensity (26 psi), or three medium intensity blasts (26 psi × 3). After recovery, all subjects were given visual discrimination tasks of increasing complexity, until mastery. After behavioral training, visual function was assessed via spectral-domain optical coherence tomography and pattern electroretinogram, and the extent of retinal damage was quantified via immunohistochemistry of retinal ganglion cells. ResultsNone of the measures assessing visual function revealed significant differences as a function of blast intensity/quantity. Behavioral training did not disclose short-term effects of blast in general motivation or the development of anticipatory responding. No differences in general learning ability and the number of perseverative errors were observed. However, behavioral training found effects of blast in attentional function; relative to controls, subjects that received blasts were faster in learning to attend to informative (over non-informative) cues in the most difficult visual discrimination task. ConclusionBlast exposure in rats resulted in increased attention following blast, with no appreciable deficits in visual function. These results are contrary to what is often reported for human clinical populations; as such, more research bridging methodological differences is necessary.

Features of blast-induced traumatic brain injury

Traumatic brain injury, despite its prevalence and study, is the most urgent issue of medicine in clinical, social and military-medical significance. In Russia, about 500 thousand people receive a traumatic brain injury every year, and the damage to the country’s economy exceeds 500 billion rubles a year. Traumatic brain injury is damage by mechanical energy to the skull and intracranial contents (brain, meninges, vessels, cranial nerves), accompanied by clinical symptoms and, in most cases, morphological changes. Recently, blast-induced traumatic brain injury has acquired particular importance, which is due to the change in modern tactics of warfare and the predominance of explosive trauma in the structure of all injuries. The features of blast-induced traumatic brain injury are associated with a variety of factors affecting a person (shock wave, light, heat radiation, fragments, etc.). Such a multifactorial effect on a person makes it difficult to identify a blast-induced traumatic brain injury, especially a brain concussion. This is due to a possible combination of damage to different organs and systems of a person during an explosion, which can simulate or mask a brain concussion. When diagnosing a traumatic brain injury, it is especially important to assess the circumstances and information from witnesses of the event, which often presents a certain complexity in the conditions of hostilities. Currently, methods for detecting symptoms of instability, visual and disorders of other sensory systems involved in maintaining balance are considered as a promising direction for the diagnosis of mild traumatic brain injury. It is also important to note that patients who have suffered a traumatic brain injury have a risk of developing neurodegenerative diseases. All this further emphasizes the relevance of traumatic brain injury and the existing need to develop an optimal algorithm for the examination of such patients.

Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats.

Abstract Traumatic brain injury-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines, especially epinephrine, although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain injury. Epinephrine has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate, blood pressure, and blood flow to the hindlimb muscles. Therefore, the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in several function-specific central nervous system regions in rats. Following three repeated blast injuries at three-day intervals, the hippocampus, motor cortex, locus coeruleus, vestibular nuclei, and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector coupled with high-performance liquid chromatography. Our results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age- and sex-matched sham controls. In other function-specific central nervous system regions, although the epinephrine levels were slightly altered following blast-induced traumatic brain injury, they were not statistically significant. These results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular function. This is the first report to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.

Single-nucleus transcriptomic mapping of blast-induced traumatic brain injury in mice hippocampus

As a significant type of traumatic brain injury (TBI), blast-induced traumatic brain injury (bTBI) frequently results in severe neurological and psychological impairments. Due to its unique mechanistic and clinical features, bTBI presents diagnostic and therapeutic challenges compared to other TBI forms. The hippocampus, an important site for secondary injury of bTBI, serves as a key niche for neural regeneration and repair post-injury, and is closely associated with the neurological outcomes of bTBI patients. Nonetheless, the pathophysiological alterations of hippocampus underpinning bTBI remain enigmatic, and a corresponding transcriptomic dataset for research reference is yet to be established. In this investigation, the single-nucleus RNA sequencing (snRNA-seq) technique was employed to sequence individual hippocampal nuclei of mice from bTBI and sham group. Upon stringent quality control, gene expression data from 17,278 nuclei were obtained, with the dataset’s reliability substantiated through various analytical methods. This dataset holds considerable potential for exploring secondary hippocampal injury and neurogenesis mechanisms following bTBI, with important reference value for the identification of specific diagnostic and therapeutic targets for bTBI.

Raman spectroscopic diagnosis of blast-induced traumatic brain injury in rats combined with machine learning

Blast-induced traumatic brain injury (bTBI) is a kind of nervous system disease, which results in a major health and economic problem to society. However, the rapid and label-free detection method with high sensitivity is still in great demand for the diagnosis of bTBI, especially for mild bTBI. In this paper, we report a new strategy for bTBI diagnosis through hippocampus and hypothalamus tissues based on Raman spectroscopy. The spectral characteristics of hippocampus and hypothalamus tissues of experimental bTBI in rats have been investigated for mild and moderate degrees at 3 h, 6 h, 24 h, 48 h, 72 h after blast exposure. The results show that the Raman spectra of mild and moderate bTBIs in 300–1700 cm−1 and 2800–3000 cm−1 regions exhibit significant differences at different time points compared with the control group. The main reason is the content change of proteins and lipids in hippocampus and hypothalamus tissues after bTBI. Moreover, four machine learning algorithms are used to automatically identify mild and moderate bTBIs at different time points (a total of 11 groups). The highest diagnostic accuracies are up to 95.3% and 88.5% based on Raman spectra of hippocampus and hypothalamus tissue, respectively. In addition, the classification performance of linear discriminant analysis classifier has been improved after data fusion. It is suggested that there has great potential as an alternative method for high-sensitive, rapid, label-free, economical diagnosis of bTBI.

Activation of autophagy after blast-induced traumatic brain injury in mice.

Injury mechanism and treatment of blast-induced traumatic brain injury (bTBI) has not made a breakthrough so far. Previous reports demonstrate autophagy is involved in regulating the pathophysiological process after TBI. Therefore, this study explored whether autophagy was activated after bTBI. A total of 108 mice were divided randomly into six groups: 6 h, 1 d, 3 d, 7 d, 14 d after bTBI groups and sham group. The protein levels of anti-microtubule associated protein 1 light chain 3B (LC3B, hereafter referred to as LC3), beclin1 and p62 were detected using western blot. Moreover, HO-1 and Nrf2 were localized using histologic staining. Immunofluorescence of LC3 and immunohistochemistry of beclin1 were performed. The autophagy-related ultrastructure was observed by TEM. LC3-II and beclin1 reached their peak on day 3 after bTBI, while p62 showed a continuous downward trend. Immunofluorescence and immunohistochemistry also confirmed that the expression levels of LC3 and beclin1 were the highest at 3 days after bTBI. Autophagic vesicles containing lysosomes or digestive residual structures were observed then. Autophagy was induced in the frontal lobe tissues of bTBI mice induced by moderate-intensity explosion, with a peak at 3d and a gradual decline thereafter.

A critical review of experimental analyses performed on animals, post-mortem human subjects, and substitutes to explore primary blast-induced Traumatic Brain Injuries

Although blast-induced Traumatic Brain Injury (bTBI) has become a signature wound of conflict, its cause is not yet fully understood. Regarding primary blast injuries, i.e., those caused by the propagation of shock waves in the body, four direct and two indirect injury mechanisms have been mainly proposed in the literature. Since numerous authors have exposed instrumented animals, Post-Mortem Human Subjects (PMHS), and head substitutes to blast conditions, the aim of this review is to classify them in terms of threat, instrumentation, and investigated mechanisms. In the first part, data are collected from 6 studies on PMHS, 1 on primates, 11 on rodents, and 6 on swine for comparison purposes. Peak amplitudes of reflected pressures, intracranial pressures and cranial strains are extracted and analyzed to establish trends. Despite the small number of comparable studies, several similarities can be highlighted. Indeed, the analyses revealed a dose-response effect for most measurements. The results also depend on the orientation of the subject (forward, backward, and sideways) for the PMHS, primates, and swine. The second goal of this review is to evaluate the behavior of substitutes developed to replace PMHS experiments. Shell strains and internal pressures are thus collected on 19 geometric and anthropomorphic substitutes to assess whether they faithfully represent a human head. The results showed that these substitutes are for the most part not properly designed and therefore cannot yet reliably replace PMHS experimental data.