Previous neuropathological studies regarding traumatic brain injury have primarily focused on changes in large structures, for example, the clinical prognosis after cerebral contusion, intrace- rebral hematoma, and ep...Previous neuropathological studies regarding traumatic brain injury have primarily focused on changes in large structures, for example, the clinical prognosis after cerebral contusion, intrace- rebral hematoma, and epidural and subdural hematoma. In fact, many smaller injuries can also lead to severe neurological disorders. For example, cerebral microbleeds result in the dysfunc- tion of adjacent neurons and the disassociation between cortex and subcortical structures. These tiny changes cannot be adequately visualized on CT or conventional MRI. In contrast, gradient echo sequence-based susceptibility-weighted imaging is very sensitive to blood metabolites and microbleeds, and can be used to evaluate traumatic cerebral microbleeds with high sensitivity and accuracy. Cerebral microbleed can be considered as an important imaging marker for dif- fuse axonal injury with potential relevance for prognosis. For this reason, based on experimental and clinical studies, this study reviews the role of imaging data showing traumatic cerebral microbleeds in the evaluation of cerebral neuronal injury and neurofunctional loss.展开更多
Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the...Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the development of functional impairments. However, there are currently no effective therapeutic interventions that improve brain outcomes following TBI. As a result, a number of experimental TBI models have been developed to recapitulate TBI injury mechanisms and to test the efficacy of potential therapeutics. The pig model has recently come to the forefront as the pig brain is closer in size, structure, and composition to the human brain compared to traditional rodent models, making it an ideal large animal model to study TBI pathophysiology and functional outcomes. This review will focus on the shared characteristics between humans and pigs that make them ideal for modeling TBI and will review the three most common pig TBI models–the diffuse axonal injury, the controlled cortical impact, and the fluid percussion models. It will also review current advances in functional outcome assessment measures and other non-invasive, translational TBI detection and measurement tools like biomarker analysis and magnetic resonance imaging. The use of pigs as TBI models and the continued development and improvement of translational assessment modalities have made significant contributions to unraveling the complex cascade of TBI sequela and provide an important means to study potential clinically relevant therapeutic interventions.展开更多
Neuroinflammation is initiated as a result of traumatic brain injury and can exacerbate evolving tissue pathology.Immune cells respond to acute signals from damaged cells,initiate neuroinflammation,and drive the patho...Neuroinflammation is initiated as a result of traumatic brain injury and can exacerbate evolving tissue pathology.Immune cells respond to acute signals from damaged cells,initiate neuroinflammation,and drive the pathological consequences over time.Importantly,the mechanism(s)of injury,the location of the immune cells within the brain,and the animal species all contribute to immune cell behavior following traumatic brain injury.Understanding the signals that initiate neuroinflammation and the context in which they appear may be critical for understanding immune cell contributions to pathology and regeneration.Within this paper,we review a number of factors that could affect immune cell behavior acutely following traumatic brain injury.展开更多
The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans,while severe controlled cortical impact can produce a severe traumatic brain injury model u...The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans,while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters.In this study,we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences.The severe controlled cortical impact model was produced by an electronic controlled cortical impact device,while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube.Body temperature and mortality were recorded,and neurological deficits were assessed with the modified neurological severity score.Brain edema and bloodbrain barrier damage were evaluated by assessing brain water content and Evans blue extravasation.In addition,a cytokine array kit was used to detect inflammatory cytokines.Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining.Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations.More severe motor dysfunction was observed in the severe controlled cortical impact model,while more severe cognitive dysfunction was observed in the severe free weight drop model.Brain edema,inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group.The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage,with higher mortality and lower repeatability compared with the severe controlled cortical impact group.Severe brainstem damage was not found in the severe controlled cortical impact model.These results indicate that the severe controlled cortical impact model is relat展开更多
Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency.Critical illness-related corticosteroid insufficiency can easily occur after traumati...Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency.Critical illness-related corticosteroid insufficiency can easily occur after traumatic brain injury,but few studies have examined this occurrence.A multicenter,prospective,cohort study was performed to evaluate the function of the hypothalamic-pituitary-adrenal axis and the incidence of critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury.One hundred and forty patients with acute traumatic brain injury were enrolled from the neurosurgical departments of three tertiary-level hospitals in China,and the critical illness-related corticosteroid insufficiency incidence,critical-illness-related corticosteroid insufficiency-related risk factors,complications,and 28-day mortality among these patients was recorded.Critical illness-related corticosteroid insufficiency was diagnosed in patients with plasma total cortisol levels less than 10μg/dL(275.9 nM)on post-injury day 4 or when serum cortisol was insufficiently suppressed(less than 50%)during a dexamethasone suppression test on post-injury day 5.The results demonstrated that critical illness-related corticosteroid insufficiency occurred during the sub-acute phase of traumatic brain injury in 5.6%of patients with mild injury,22.5%of patients with moderate injury,and 52.2%of patients with severe injury.Traumatic brain injury-induced critical illness-related corticosteroid insufficiency was strongly correlated to injury severity during the sub-acute stage of traumatic brain injury.Traumatic brain injury patients with critical illness-related corticosteroid insufficiency frequently presented with hemorrhagic cerebral contusions,diffuse axonal injury,brain herniation,and hypotension.Differences in the incidence of hospital-acquired pneumonia,gastrointestinal bleeding,and 28-day mortality were observed between patients with and without critical illness-related corticosteroid insufficiency dur展开更多
Because diffuse axonal injury（DAI）lacks specific clinical manifestations,it is difficult to evaluate DAI using computer tomography or conventional magnetic resonance imaging（MRI）.This study investigated the value ...Because diffuse axonal injury（DAI）lacks specific clinical manifestations,it is difficult to evaluate DAI using computer tomography or conventional magnetic resonance imaging（MRI）.This study investigated the value of magnetic resonance techniques using fluid-attenuated inversion recovery（FLAIR）and proton magnetic resonance spectroscopy（1HMRS）for diagnosing DAI.The corpus callosum and basal nuclei were analyzed using morphological and functional imaging.Similar to the DAI group,the non-typical DAI group exhibited similar lesion characteristics on FLAIR,as well as post-injury neurochemical and molecular changes in the corpus callosum,as detected by 1HMRS.However,there were differences in degree and severity of injury.Compared to conventional MRI,FLAIR significantly increased lesion detection.1HMRS determined biochemical metabolism changes in midline structures following DAI,which resulted in increased diagnosis of non-typical DAI,which displayed similar lesion distribution,morphology,and function as DAI.Thus,the experiment proved the value of FLAIR and 1HMRS in non-typical DAI.展开更多
基金supported by grants from the State-Funded Construction Projects Key Clinical Specialist(2013-2015)the Hunan Provincial Science and Technology Department,No.2009FJ3092
文摘Previous neuropathological studies regarding traumatic brain injury have primarily focused on changes in large structures, for example, the clinical prognosis after cerebral contusion, intrace- rebral hematoma, and epidural and subdural hematoma. In fact, many smaller injuries can also lead to severe neurological disorders. For example, cerebral microbleeds result in the dysfunc- tion of adjacent neurons and the disassociation between cortex and subcortical structures. These tiny changes cannot be adequately visualized on CT or conventional MRI. In contrast, gradient echo sequence-based susceptibility-weighted imaging is very sensitive to blood metabolites and microbleeds, and can be used to evaluate traumatic cerebral microbleeds with high sensitivity and accuracy. Cerebral microbleed can be considered as an important imaging marker for dif- fuse axonal injury with potential relevance for prognosis. For this reason, based on experimental and clinical studies, this study reviews the role of imaging data showing traumatic cerebral microbleeds in the evaluation of cerebral neuronal injury and neurofunctional loss.
文摘Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the development of functional impairments. However, there are currently no effective therapeutic interventions that improve brain outcomes following TBI. As a result, a number of experimental TBI models have been developed to recapitulate TBI injury mechanisms and to test the efficacy of potential therapeutics. The pig model has recently come to the forefront as the pig brain is closer in size, structure, and composition to the human brain compared to traditional rodent models, making it an ideal large animal model to study TBI pathophysiology and functional outcomes. This review will focus on the shared characteristics between humans and pigs that make them ideal for modeling TBI and will review the three most common pig TBI models–the diffuse axonal injury, the controlled cortical impact, and the fluid percussion models. It will also review current advances in functional outcome assessment measures and other non-invasive, translational TBI detection and measurement tools like biomarker analysis and magnetic resonance imaging. The use of pigs as TBI models and the continued development and improvement of translational assessment modalities have made significant contributions to unraveling the complex cascade of TBI sequela and provide an important means to study potential clinically relevant therapeutic interventions.
基金supported by the Department of Veterans Affairs,USA(Merit Review I01-RX001097&I01-BX003748)
文摘Neuroinflammation is initiated as a result of traumatic brain injury and can exacerbate evolving tissue pathology.Immune cells respond to acute signals from damaged cells,initiate neuroinflammation,and drive the pathological consequences over time.Importantly,the mechanism(s)of injury,the location of the immune cells within the brain,and the animal species all contribute to immune cell behavior following traumatic brain injury.Understanding the signals that initiate neuroinflammation and the context in which they appear may be critical for understanding immune cell contributions to pathology and regeneration.Within this paper,we review a number of factors that could affect immune cell behavior acutely following traumatic brain injury.
基金supported by the National Natural Science Foundation of China,No.81671221(to RCJ)
文摘The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans,while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters.In this study,we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences.The severe controlled cortical impact model was produced by an electronic controlled cortical impact device,while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube.Body temperature and mortality were recorded,and neurological deficits were assessed with the modified neurological severity score.Brain edema and bloodbrain barrier damage were evaluated by assessing brain water content and Evans blue extravasation.In addition,a cytokine array kit was used to detect inflammatory cytokines.Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining.Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations.More severe motor dysfunction was observed in the severe controlled cortical impact model,while more severe cognitive dysfunction was observed in the severe free weight drop model.Brain edema,inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group.The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage,with higher mortality and lower repeatability compared with the severe controlled cortical impact group.Severe brainstem damage was not found in the severe controlled cortical impact model.These results indicate that the severe controlled cortical impact model is relat
基金supported by the National Natural Science Foundation of China,No.81671902(to XC)81501704(to YC)+3 种基金the Project of Tianjin Applied Basic and Cutting-edge Technological Research of China,No.17JCYBJC25200(to XC)15JCQNJC44900(to YC)Tianjin Health Care Elite Prominent Young Doctor Development Program(to XC)the Young and Middle-aged Backbone Innovative Talent Program(to XC)
文摘Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency.Critical illness-related corticosteroid insufficiency can easily occur after traumatic brain injury,but few studies have examined this occurrence.A multicenter,prospective,cohort study was performed to evaluate the function of the hypothalamic-pituitary-adrenal axis and the incidence of critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury.One hundred and forty patients with acute traumatic brain injury were enrolled from the neurosurgical departments of three tertiary-level hospitals in China,and the critical illness-related corticosteroid insufficiency incidence,critical-illness-related corticosteroid insufficiency-related risk factors,complications,and 28-day mortality among these patients was recorded.Critical illness-related corticosteroid insufficiency was diagnosed in patients with plasma total cortisol levels less than 10μg/dL(275.9 nM)on post-injury day 4 or when serum cortisol was insufficiently suppressed(less than 50%)during a dexamethasone suppression test on post-injury day 5.The results demonstrated that critical illness-related corticosteroid insufficiency occurred during the sub-acute phase of traumatic brain injury in 5.6%of patients with mild injury,22.5%of patients with moderate injury,and 52.2%of patients with severe injury.Traumatic brain injury-induced critical illness-related corticosteroid insufficiency was strongly correlated to injury severity during the sub-acute stage of traumatic brain injury.Traumatic brain injury patients with critical illness-related corticosteroid insufficiency frequently presented with hemorrhagic cerebral contusions,diffuse axonal injury,brain herniation,and hypotension.Differences in the incidence of hospital-acquired pneumonia,gastrointestinal bleeding,and 28-day mortality were observed between patients with and without critical illness-related corticosteroid insufficiency dur
基金the Grant from Chongqing Board of Health, No. 2009-2-391, No. 06-2-175the Grant from Chongqing Medical University, No. XBYB2007005
文摘Because diffuse axonal injury（DAI）lacks specific clinical manifestations,it is difficult to evaluate DAI using computer tomography or conventional magnetic resonance imaging（MRI）.This study investigated the value of magnetic resonance techniques using fluid-attenuated inversion recovery（FLAIR）and proton magnetic resonance spectroscopy（1HMRS）for diagnosing DAI.The corpus callosum and basal nuclei were analyzed using morphological and functional imaging.Similar to the DAI group,the non-typical DAI group exhibited similar lesion characteristics on FLAIR,as well as post-injury neurochemical and molecular changes in the corpus callosum,as detected by 1HMRS.However,there were differences in degree and severity of injury.Compared to conventional MRI,FLAIR significantly increased lesion detection.1HMRS determined biochemical metabolism changes in midline structures following DAI,which resulted in increased diagnosis of non-typical DAI,which displayed similar lesion distribution,morphology,and function as DAI.Thus,the experiment proved the value of FLAIR and 1HMRS in non-typical DAI.
