Exploring cerebral structural and functional abnormalities in a mouse model of post-traumatic headache induced by mild traumatic brain injury

Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely unknown.Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH.In this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery.Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage.Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of PTH.Additionally,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying PTH.Moreover,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH.Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.

Elevated NKCC1 transporter expression facilitates early post-traumatic brain injury seizures

As a leading cause for morbidity and mortality in young adults,traumatic brain injury（TBI）,along with the poorly understood TBI-related seizures inducing their predispositions,pose a major health and socioeconomic problem in the world（Huang,2013）.

Dementia in military and veteran populations:a review of risk factors—traumatic brain injury,post-traumatic stress disorder,deployment,and sleep

The military population face a unique set of risk factors that may increase the risk of being diagnosed with dementia.Traumatic brain injury(TBI)and post-traumatic stress disorder(PTSD)have a higher prevalence in this group in comparison to the civilian population.By delving into the individual relationships between TBI and dementia,and PTSD and dementia,we are able to better explore dementia in the military and veteran populations.While there are some inconsistencies in results,the TBI-dementia association has become more widely accepted.Moderate-tosevere TBI has been found to increase the risk of being diagnosed with Alzheimer’s disease.A correlation between PTSD and dementia has been established,however,whether or not it is a causal relationship remains unclear.Factors such as blast,combat and chemical exposure may occur during a deployment,along with TBI and/or PTSD diagnosis,and can impact the risk of dementia.However,there is a lack of literature exploring the direct effects of deployment on dementia risk.Sleep problems have been observed to occur in those following TBI,PTSD and deployment.Poor sleep has been associated with possible dementia risk.Although limited studies have focused on the link between sleep and dementia in military and veteran populations,sleep is a valuable factor to study due to its association and interconnection with other military/veteran factors.This review aims to inform of various risk factors to the cognitive health of military members and veterans:TBI,PTSD,deployment,and sleep.

Injury of the dentatorubrothalamic tract in patients with post-traumatic tremor following mild traumatic brain injury: a case-control study

Post-traumatic movement disorder is one of the sequelae of traumatic brain injury. The dentatorubrothalamic tract(DRTT) is reported to be involved in the control of movement. Therefore, injury of the DRTT can be accompanied by abnormal movements, including ataxia, tremor, or dystonia. We investigated DRTT injuries in 27 patients who showed post-traumatic tremor in at least one of four extremities following mild traumatic brain injury. We classified DRTT injuries based on diffusion tensor tractography parameters and configuration: type A: the DRTT showed narrowing, type B: the DRTT showed partial tearing, and type C: the DRTT showed discontinuation. Fractional anisotropy and fiber number of the DRTT were significantly decreased in patients compared with the healthy controls. Based on our DRTT injury classification, among the 54 hemispheres of the 27 patients, type A injury occurred in 22 hemispheres(40.7%) of 17 patients, type B injury was present in 15 hemispheres(27.7%) of 10 patients, and type C injury was observed in 8 hemispheres(14.8%) of 6 patients. Our results suggest that diffusion tensor tractography-based evaluation of the DRTT would be useful when determining cause of post-traumatic tremor in patients with mild traumatic brain injury. The study protocol was approved by the Institutional Review Board of Yeungnam University Hospital(YUMC-2018-09-007) on September 5, 2018.

Post-Concussion Syndrome after a Mild Traumatic Brain Injury: A Minefield for Clinical Practice

In this clinical practice review, the controversies and difficulties managing post concussion symptoms following mild traumatic brain injury are discussed. Based on considerable clinical experience in a designated Concussion Clinic, the authors (a neuropsychologist, a psychiatrist, and a neurologist) review relevant literature and issues for clinical practice, particularly with respect to understanding risk factors for and vulnerability to, development of chronic post-concussion symptoms. We contend it is not just the kind of head that matters but also the kind of complications, the kind of outcomes and the kind of management that can influence injury recovery. Given these complexities, a bio-psychosocial conceptualization of chronic post-concussion syndrome is appropriate. Though understanding is still elusive, management should not be biased by physiogenic or psychogenic aetiological theories for management needs to address patient reported outcomes regardless of underpinning aetiology.

Effects of therapeutic horseback riding on post-traumatic stress disorder in military veterans

Background:Large numbers of post-deployment U.S.veterans are diagnosed with post-traumatic stress disorder(PTSD)and/or traumatic brain injury(TBI),leading to an urgent need for effective interventions to reduce symptoms and increase veterans’coping.PTSD includes anxiety,flashbacks,and emotional numbing.The symptoms increase health care costs for stress-related illnesses and can make veterans’civilian life difficult.Methods:We used a randomized wait-list controlled design with repeated measures of U.S.military veterans to address our specific aim to test the efficacy of a 6-week therapeutic horseback riding(THR)program for decreasing PTSD symptoms and increasing coping self-efficacy,emotion regulation,social and emotional loneliness.Fiftyseven participants were recruited and 29 enrolled in the randomized trial.They were randomly assigned to either the horse riding group(n=15)or a wait-list control group(n=14).The wait-list control group experienced a 6-week waiting period,while the horse riding group began THR.The wait-list control group began riding after 6 weeks of participating in the control group.Demographic and health history information was obtained from all the participants.PTSD symptoms were measured using the standardized PTSD Checklist-Military Version(PCL-M).The PCL-M as well as other instruments including,The Coping Self Efficacy Scale(CSES),The Difficulties in Emotion Regulation Scale(DERS)and The Social and Emotional Loneliness Scale for Adults-short version(SELSA)were used to access different aspects of individual well-being and the PTSD symptoms.Results:Participants had a statistically significant decrease in PTSD scores after 3 weeks of THR(P≤0.01)as well as a statistically and clinically significant decrease after 6 weeks of THR(P≤0.01).Logistic regression showed that participants had a 66.7%likelihood of having lower PTSD scores at 3 weeks and 87.5%likelihood at 6 weeks.Under the generalized linear model(GLM),our ANOVA findings for the coping self-efficacy,emotion regulation,and social and emotional loneliness did not reach statistical significance.The results for coping self-efficacy and emotion regulation trended in the predicted direction.Results for emotional loneliness were opposite the predicted direction.Logistic regression provided validation that outcome effects were caused by riding longer.Conclusion:The findings suggest that THR may be a clinically effective intervention for alleviating PTSD symptoms in military veterans.

Lumboperitoneal shunts for the treatment of post-traumatic hydrocephalus

Objective: To assess the effectiveness and safety of lumboperitoneal shunt for treatment of post-traumatic hydrocephalus(PTH).Methods: A retrospective analysis of medical records of patients with lumboperitoneal shunts admitted in Shanghai Tenth People's Hospital from January 2014 to March 2017 was done.Experience with lumboperitoneal shunt placement for PTH was reviewed.The diagnosis of PTH was based on ventricular enlargement with the Evans' index(EI>0.3) before shunt implantation.Patients were evaluated for improvements in Glasgow Coma Scale(GCS), Glasgow Outcome Scale(GOS), and EI after shunt placement.Results: Totally, the study included 34 PTH patients with the average age of 49.32 years(range: 9–67 years).The average follow-up period was(3.9±3.5) months.Before lumboperitoneal shunt, the GOS score was(4±1), the GCS score was(8.53±3.38), and the EI score was(0.40±0.08).After shunt implantation, the GOS score was(3±1), the GCS score was(10.29±3.15), and the EI score was(0.34±0.13), respectively(P<0.05).Before lumboperitoneal shunt, 24(70.58%) patients had a GOS score of 4(vegetative state), and 10(29.42%) patients had a GOS score of 3(severe disabled).After lumboperitoneal shunt, 18(52.94%) patients had improvement in GOS(11 patients improve from GOS 4 to GOS 3, 5 patients from GOS 3 to GOS 2 and 2 patients from GOS 3 to GOS 1), 22(64.71%) patients achieved improvement in their GCS(14 patients GCS improvements ≥2 and 8 patients GCS improvement=1), 21(61.76%) patients had EI improvement(18 patients with EI<0.3).There was no complication in this study.Conclusion: Lumboperitoneal shunt placement is safe and effective for PTH, and serious complications are not observed.

An effective initial polytherapy for children with West syndrome

Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy, seizures recur in 33% of patients who initially respond to adrenocorticotropic hormone monotherapy, and side effects are relatively common during adrenocorticotropic hormone treatment. Topiramate, vitamin B6, and immunoglobulin are effective in some children with infantile spasms. In the present study, we hypothesized that combined therapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin would effectively treat infantile spasms and have mild adverse effects. Thus, 51 children newly diagnosed with West syndrome including infantile spasms were enrolled and underwent polytherapy with the four drugs. Electroencephalographic hypsarrhythmia was significantly improved in a majority of patients, and these patients were seizure-free, had mild side effects, and low recurrence rates. The overall rates of effective treatment and loss of seizures were significantly higher in cryptogenic children compared with symptomatic children. The mean time to loss of seizures in cryptogenic children was significantly shorter than in symptomatic patients. These findings indicate that initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin Be, and immunoglobulin effectively improves the prognosis of infantile spasms, and its effects were superior in cryptogenic children to symptomatic children.

Effects of diazepam on glutamatergic synaptic transmission in the hippocampal CA1 area of rats with traumatic brain injury

The activity of the Schaffer collaterals of hippocampal CA3 neurons and hippocampal CA1 neurons has been shown to increase after lfuid percussion injury. Diazepam can inhibit the hy-perexcitability of rat hippocampal neurons after injury, but the mechanism by which it affects excitatory synaptic transmission remains poorly understood. Our results showed that diazepam treatment signiifcantly increased the slope of input-output curves in rat neurons after lfuid per-cussion injury. Diazepam signiifcantly decreased the numbers of spikes evoked by super stimuli in the presence of 15 μmol/L bicuculline, indicating the existence of inhibitory pathways in the injured rat hippocampus. Diazepam effectively increased the paired-pulse facilitation ratio in the hippocampal CA1 region following fluid percussion injury, reduced miniature excitatory postsynaptic potentials, decreased action-potential-dependent glutamine release, and reversed spontaneous glutamine release. These data suggest that diazepam could decrease the lfuid per-cussion injury-induced enhancement of excitatory synaptic transmission in the rat hippocampal CA1 area.

Correlation between synaptic protein expression and synaptic reorganization in the hippocampal CA3 region in a rat model of post-traumatic epilepsy

Postsynaptic density protein-95 and synaptophysin participate in synaptic reorganization in the forebrain of epilepsy models. However, the time-effect relationship between dynamic synapsin expression in hippocampus and synaptic reorganization in the post-traumatic epilepsy model remains unclear. FeCI2 was injected into the hippocampal CA3 region of the right forebrain in rats to induce post-traumatic epilepsy. Postsynaptic density protein-95 and synaptophysin expression was detected using immunohistochemistry. Epileptiform discharge induced by FeCI2 injection was determined in rat forebrain neurons, revealing decreased postsynaptic density protein-95 expression at 24 hours and lowest levels at 7 days. Synaptophysin expression was markedly reduced at 24 hours, but increased at 7 days. Postsynaptic density protein-95 and synaptophysin expression was consistent with abnormal mossy fiber sprouting and synaptic reorganization following neuronal injury in the hippocampal CA3 region of FeCI2-induced epilepsy models.

创伤性脑损伤后阵发性交感神经过度兴奋综合征的研究进展

阵发性交感神经过度兴奋综合征(PSH)是中重度创伤性脑损伤(TBI)后一种常见的并发症,以同时、阵发性的交感神经兴奋性增加(高热、血压升高、心率增快、呼吸急促、大汗)和姿势或肌张力障碍为特征。PSH的临床表现存在个体差异,症状缺乏特异性,早期易与脓毒症、癫痫等疾病相混淆。目前PSH的发病机制尚未明确,诊断主要通过临床表现及排除其他疾病,因此易造成误诊及治疗延迟,最终阻碍TBI患者的康复过程。本文就创伤性脑损伤后PSH的临床特点、发病机制、诊断、治疗等进行综述,以期为PSH的早期诊断、治疗提供指导。

代谢组学在体外循环心脏手术器官损伤中的研究进展

体外循环(CPB)主要应用于心脏手术,CPB会造成脑、心、肾等重要脏器的损害,产生相关的并发症。代谢组学是研究生物体受外部刺激所产生的全部变化的代谢产物的科学,CPB后机体的代谢物成分会发生变化。研究心脏手术围术期的代谢变化,可以为疾病的发病机制提供重要的见解,并有潜力识别新的生物标志物。本综述主要介绍代谢组学的现状,以及其在CPB心脏手术对脑、心、肾、肺等重要脏器损伤中的研究进展,并就代谢组学在该领域的未来做一展望。

推拿联合Bobath疗法在小儿运动发育迟缓康复治疗中的应用效果

目的观察推拿联合Bobath疗法在小儿运动发育迟缓康复治疗中的应用效果。方法选取2022年1月至2023年7月肇庆市第二人民医院儿童保健科收治的30例运动发育迟缓小儿为研究组,采用推拿联合Bobath疗法,选取2019年1月至2021年12月的30例患儿为对照组,单纯采用Bobath疗法。比较两组患儿治疗前后的五大区发育商和治疗效果。结果两组治疗后的五大区发育商(大运动、精细运动、语言、适应能力及社交能力)高于治疗前,且研究组精细运动、语言、适应能力及社交能力评分高于对照组,差异有统计学意义(P<0.05);两组患儿的治疗总有效率比较,差异无统计学意义(P>0.05);但研究组的治疗效果整体优于对照组,差异有统计学意义(P<0.05)。结论推拿联合Bobath疗法在运动发育迟缓小儿的语言、适应能力及社交能力康复治疗中较单纯Bobath疗法更具有优势,值得临床应用和基层技术推广。

严重创伤性颅脑损伤患者发生急性呼吸窘迫综合征的危险因素及预后分析

目的探讨严重创伤性颅脑损伤(sTBI)后急性呼吸窘迫综合征(ARDS)发生的危险因素并对患者预后进行分析。方法回顾性纳入2018年1月至2024年1月解放军东部战区总医院单纯性sTBI患者共328例,根据受伤后7 d内是否出现ARDS分为ARDS组(107例)和非ARDS组(221例);对患者一般信息(年龄、性别、吸烟情况、糖尿病、高血压等)、创伤程度[头颅简明损伤评分(AIS)、格拉斯哥昏迷评分(GCS)、输血及血小板输注情况]以及相关血生化指标[包括碱剩余(BE)、血肌酐(SCr)、尿素氮、降钙素原(PCT)等]采用单因素和多因素法评估sTBI发生ARDS的危险因素,绘制风险预测模型,并对患者预后进行分析。结果几乎所有sTBI患者出现ARDS的时间都是在损伤后7 d内,年龄>55岁、血糖、PCT水平、休克、输注血小板>10 U、GCS评分、血清BE<-6 mmol/L、SCr及血尿素氮组间比较差异有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,年龄>55岁、GCS低评分(<8分)、休克、输注血小板>10 U、血PCT≥10.01μg/L是sTBI后ARDS发生的危险因素,ARDS组患者病死率(61.5%vs.26.4%)、平均住院时间(d:14.8±3.4 vs.11.4±3.6)、机械通气持续时间(d:11.6±2.8 vs.7.8±2.1)等均高于未出现ARDS组(P<0.05)。结论GCS低评分(<8分)、年龄>55岁、输注血小板>10 U、休克、血PCT≥10.01μg/L是sTBI后ARDS发生的独立危险因素。对存在高危因素患者应早期识别、及时联合干预,有可能降低并发症的发生,改善患者预后。

急性脑损伤并发ARDS患者中乳酸水平与EIT中背侧通气分布关联性的临床研究

目的通过电阻抗断层成像(EIT)研究急性脑损伤(ABI)并发急性呼吸窘迫综合征(ARDS)患者的动脉血气相关指标与背侧肺通气及肺血流异常的相关性。方法收集2020年5月至2021年12月在复旦大学附属中山医院重症医学科12例ABI并发ARDS患者的EIT监测肺通气与肺血流数据,以及该时段患者动脉血气与炎症相关临床指标。根据入组患者的背侧通气感兴趣区域(ROI)之和(ROI3+ROI4),以中位数为界将患者分为背侧通气低水平组(n=6)和背侧通气高水平组(n=6)。根据动脉血二氧化碳分压(PaCO_(2))水平,以中位数为分界点分为PaCO_(2)低通气组(n=6)和PaCO_(2)高通气组(n=6)。对患者背侧通气ROI之和与乳酸等指标进行相关性分析,并计算患者EIT下死腔、分流比率及通气血流匹配水平。结果在ABI并发ARDS的患者中,EIT背侧通气之和(ROI3+ROI4)与动脉血乳酸水平呈负相关(r=-0.700,P=0.011)。背侧通气低水平组和背侧通气高水平组动脉血气指标及炎症相关指标比较差异均无统计学意义(P>0.05)。PaCO_(2)低通气组和PaCO_(2)高通气组动脉血气指标及炎症相关指标比较差异无统计学意义(P>0.05)。根据可获取的5例EIT肺通气及灌注成像数据显示,患者的平均通气血流匹配水平为(49±11)%(<60%),存在通气血流匹配显著失调。结论ABI并发ARDS患者的通气血流匹配存在显著失调,通过动脉血乳酸水平可监测背侧通气状态。

Strategies to avoid a missed diagnosis of co-occurring concussion in post-acute patients having a spinal cord injury

Research scientists and clinicians should be aware that missed diagnoses of mild-moderate traumatic brain injuries in post-acute patients having spinal cord injuries may approach 60-74% with certain risk factors, potentially causing clinical consequences for patients, and confounding the results of clinical research studies. Factors leading to a missed diagnosis may include acute trauma-related life-threatening issues, sedation/intubation, subtle neuropathology on neuroimaging, failure to collect Glasgow Coma Scale scores or duration of posttraumatic amnesia, or lack of validity of this information, and overlap in neuro-cognitive symptoms with emotional responses to spinal cord injuries. Strategies for avoiding a missed diagnosis of mild-moderate traumatic brain injuries in patients having a spinal cord injuries are highlighted in this perspective.

Brain remodeling after chronic median nerve compression in a rat model

Carpal tunnel syndrome is the most common compressive neuropathy,presenting with sensorimotor dysfunction.In carpal tunnel syndrome patients,irregular afferent signals on functional magnetic resonance imaging are associated with changes in neural plasticity during peripheral nerve injury.However,it is difficult to obtain multi-point neuroimaging data of the brain in the clinic.In the present study,a rat model of median nerve compression was established by median nerve ligation,i.e.,carpal tunnel syndrome model.Sensory cortex remodeling was determined by functional magnetic resonance imaging between normal rats and carpal tunnel syndrome models at 2 weeks and 2 months after operation.Stimulation of bilateral paws by electricity for 30 seconds,alternating with 30 seconds of rest period（repeatedly 3 times）,resulted in activation of the contralateral sensorimotor cortex in normal rats.When carpal tunnel syndrome rats received this stimulation,the contralateral cerebral hemisphere was markedly activated at 2 weeks after operation,including the primary motor cortex,cerebellum,and thalamus.Moreover,this activation was not visible at 2 months after operation.These findings suggest that significant remodeling of the cerebral cortex appears at 2 weeks and 2 months after median nerve compression.

Clinical analysis of the syndrome of inappropriate antidiuretic hormone secretion after brain injury

Objective: To study the diagnosis and treatment of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) after brain injury. Methods: A retrospective analysis was conducted on 12 patients suffered from SIADH after brain injury. The clinical features of these patients were similar to those of common hyponatremia. Most of the hyponatremia were detected by routine examinations. Supplement of salt as the initial treatment was used in these patients. If natremia did not rise or descended 2 3 days after treatment, SIADH was considered or diagnosed. Treatment scheme should be adjusted to limit water and natrium instead of supplying salt. Frusemide and albumin were the first choice for dehydration therapy. Results: 24 48 hours after limiting water and natrium, 12 patients natremia level was back to normal. Eight out of 12 patients were corrected completely in 1 week, 1 in 14 days, and 1 in 3 months after injury. Conclusions: Diagnosis of SIADH is difficult before treatment though effective treatment can be obtained if we adopt correct strategy. In these patients, the diagnosis of SIADH is confirmed in the course of treatment.

Brain-derived neurotrophic factor and Bcl-2 expression in rat brain areas following chronic morphine treatment

The ventral tegmental area and the locus coeruleus are associated with psychological and physical dependence of opioid addiction. To date, very little is known about brain-derived neurotrophic factor （BDNF） and Bcl-2 gene and protein changes following morphine addiction. The present study utilized immunohistochemistry and in situ hybridization techniques, which revealed that there were increased BDNF levels, but decreased Bcl-2 levels in the prefrontal cortex, locus coeruleus, hippocampus, and the ventral tegmental area during morphine-dependence formation and abstinence. However, the levels of BDNF remained unchanged, and Bcl-2 expression was increased in the nucleus accumbens. These results showed that BDNF and Bcl-2 are involved in the development of morphine dependence, and precipitation of abstinence syndrome.