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Electroacupuncture improves cognitive function in a rat model of mild traumatic brain injury by regulating the SIRT-1/PGC-1α/mitochondrial pathway

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Chinese Medical Journal 2024年第6期137卷 711-719页

作者： Bo Jin Yemei Gao Yixian Fu Suxin Zhang Ke Zhang Yibing Su Department of Neurosurgery Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China Department of Traditional Chinese Medicine Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China Department of Cardiology Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Breast Surgical Oncology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background:mild traumatic brain injury(mTBI)is a common neurological trauma that can lead to cognitive impairment.The sirtuin-1(SIRT-1)/peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)pathway has been reported to have neuroprotective effects in rats with craniocerebral injury.We evaluated potential mechanisms underlying electroacupuncture-mediated recovery of cognitive function after mTBI,focusing on the SIRT-1/PGC-1α/mitochondrial pathway.Methods:We included forty 6-week-old male Sprague-Dawley rats in this study.Rats were randomly divided into four groups:controlled cortical impactor(CCI,n=10),sham operation(sham,n=10),electroacupuncture-treated CCI(CCI+EA,n=10),and electroacupuncture-treated sham(sham+EA,n=10)group.Randomization was performed by assigning a random number to each rat and using a random number table.The mTBI rat model was established using a controllable cortical impactor.Electroacupuncture therapy was performed on the back of rats,by inserting acupuncture needles to the specific acupoints and setting appropriate parameters for treatment.We evaluated spatial learning and memory functions with the Morris water maze test.We performed quantitative real-time polymerase chain reaction(qRT-PCR),western blotting,adenosine triphosphate(ATP)determination,and mitochondrial respiratory chain complex I(MRCC I)determination on rat hippocampal tissue.We analyzed SIRT-1/PGC-1α expression levels and the results of mitochondrial function assays,and compared differences between groups using bilateral Student’s t-tests.Results:Compared with the sham group,SIRT-1/PGC-1α expression was downregulated in the hippocampus of CCI group(P<0.01).Although this expression was upregulated following electroacupuncture,it did not reach the levels observed in the sham group(P<0.05).Compared with the sham group,MRCC I and ATP levels in the CCI group were significantly reduced,and increased after electroacupuncture(P<0.01).In the Morris water maze,electroacupuncture reduced the incubation period of rats and

关键词： Electroacupuncture Cognitive impairment Sirtuin-1 mild traumatic brain injury SIRT-1/PGC-1α/mitochondrial pathway

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Structural and functional connectivity of the whole brain and subnetworks in individuals with mild traumatic brain injury:predictors of patient prognosis

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Neural Regeneration Research 2024年第7期19卷 1553-1558页

作者： Sihong Huang Jungong Han Hairong Zheng Mengjun Li Chuxin Huang Xiaoyan Kui Jun Liu Department of Radiology The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Computer Science Aberystwyth UniversityAberystwythCeredigionUK Shenzhen Institutes of Advanced Technology Chinese Academy of SciencesShenzhenGuangdong ProvinceChina School of Computer Science and Engineering Central South UniversityChangshaHunan ProvinceChina Department of Radiology Quality Control Center of Hunan ProvinceChangshaHunan ProvinceChina Clinical Research Center for Medical Imaging of Hunan Province ChangshaHunan ProvinceChina

Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal ch

关键词： cognitive function cross-section follow-up functional connectivity graph theory longitudinal study mild traumatic brain injury prediction small-worldness structural connectivity subnetworks whole brain network

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Positron emission tomography imaging for the assessment of mild traumatic brain injury and chronic traumatic encephalopathy:recent advances in radiotracers

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Neural Regeneration Research 2022年第1期17卷 74-81页

作者： Chu-Xin Huang Yan-Hui Li Wei Lu Si-Hong Huang Meng-Jun Li Li-Zhi Xiao Jun Liu Department of Radiology the Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Department of Neurology the Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina PET-CT Center the Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina

A chronic phase following repetitive mild traumatic brain injury can present as chronic traumatic encephalopathy in some cases,which requires a neuropathological examination to make a definitive diagnosis.Positron emission tomography(PET)is a molecular imaging modality that has high sensitivity for detecting even very small molecular changes,and can be used to quantitatively measure a range of molecular biological processes in the brain using different radioactive tracers.Functional changes have also been reported in patients with different forms of traumatic brain injury,especially mild traumatic brain injury and subsequent chronic traumatic encephalopathy.Thus,PET provides a novel approach for the further evaluation of mild traumatic brain injury at molecular levels.In this review,we discuss the recent advances in PET imaging with different radiotracers,including radioligands for PET imaging of glucose metabolism,tau,amyloid-beta,γ-aminobutyric acid type A receptors,and neuroinflammation,in the identification of altered neurological function.These novel radiolabeled ligands are likely to have widespread clinical application,and may be helpful for the treatment of mild traumatic brain injury.Moreover,PET functional imaging with different ligands can be used in the future to perform largescale and sequential studies exploring the time-dependent changes that occur in mild traumatic brain injury.

关键词： amyloid-β chronic traumatic encephalopathy flumazenil fluorodeoxyglucose mild traumatic brain injury positron emission tomography tau protein traumatic brain injury

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Diffusion tensor tractography characteristics of axonal injury in concussion/mild traumatic brain injury

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Neural Regeneration Research 2022年第5期17卷 978-982页

作者： Sung Ho Jang You Sung Seo Department of Physical Medicine and Rehabilitation College of MedicineYeungnam UniversityDaeguRepublic of Korea

The main advantage of diffusion tensor tractography is that it allows the entire neural tract to be evaluated.In addition,configurational analysis of reconstructed neural tracts can indicate abnormalities such as tearing,narrowing,or discontinuations,which have been used to identify axonal injury of neural tracts in concussion patients.This review focuses on the characteristic features of axonal injury in concussion or mild traumatic brain injury(m TBI)patients through the use of diffusion tensor tractography.Axonal injury in concussion(m TBI)patients is characterized by their occurrence in long neural tracts and multiple injuries,and these characteristics are common in patients with diffuse axonal injury and in concussion(m TBI)patients with axonal injury.However,the discontinuation of the corticospinal tract is mostly observed in diffuse axonal injury,and partial tearing and narrowing in the subcortical white matter are frequently observed in concussion(m TBI)patients with axonal injury.This difference appears to be attributed to the observation that axonal injury in concussion(m TBI)patients is the result of weaker forces than those producing diffuse axonal injuries.In addition,regarding the fornix,in diffuse axonal injury,discontinuation of the fornical crus has been frequently reported,but in concussion(m TBI)patients,many collateral branches form in the fornix in addition to these findings in many case studies.It is presumed that the impact on the brain in TBI is relatively weaker than that in diffuse axonal injury,and that the formation of collateral branches occurs during the fornix recovery process.Although the occurrence of axonal injury in multiple areas of the brain is an important feature of diffuse axonal injury,case studies in concussion(m TBI)have shown that axonal injury occurs in multiple neural tracts.Because axonal injury lesions in m TBI patients may persist for approximately 10 years after injury onset,the characteristics of axonal injury in concussion(m TBI)patients,which are reviewed and c

关键词： axonal injury brain injury concussion diffusion tensor imaging diffusion tensor tractography mild traumatic brain injury neural tract

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Quetiapine augmentation of prolonged exposure therapy in veterans with PTSD and a history of mild traumatic brain injury: design and methodology of a pilot study

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Military Medical Research 2021年第1期8卷 121-131页

作者： Muhammad R.Baig Robert D.Beck Jennifer L.Wilson Jennifer A.Lemmer Adeel Meraj Eric C.Meyer Jim Mintz Alan L.Peterson John D.Roache Mental Health South Texas Veterans Healthcare System116 A7400 Merton Minter BIvdSan AntonioTX 78229USA Polytrauma Rehabilitation Center South Texas Veterans Healthcare SystemSan AntonioTXUSA Department of Psychiatry and Behavioral Sciences University of Texas Health Science Center at San AntonioSan AntonioTXUSA Department of Veterans Affairs VISN 17 Center of Excellence for Research on Returning War Veterans WacoTXUSA Central Texas Veterans Healthcare System WacoTXUSA Department of Psychology and Neuroscience Baylor UniversityWacoTXUSA Department of Epidemiology and Biostatistics University of Texas Health Science Center at San AntonioSan AntonioTXUSA Department of Psychology University of Texas at San AntonioSan AntonioUSA Department of Pharmacology University of Texas Health Science Center at San AntonioSan AntonioTXUSA

Background: Selective serotonergic reuptake inhibitors(SSRIs) are first-line pharmacologic treatments for patients with posttraumatic stress disorder(PTSD), but must be given over extended period of time before the onset of action. The use of SSRIs in PTSD patients with mild traumatic brain injury(m TBI) is problematic since SSRIs could exacerbate post-concussion syndrome(PCS) symptoms. VA/DOD guidelines identify trauma-focused psychotherapy as the best evidence-based treatment for PTSD, but overall effectiveness is limited by reduced levels of patient engagement and retention. A previous study from this research group suggested that quetiapine monotherapy, but not risperidone or valproate, could increase engagement in trauma-focused psychotherapy.Methods: We report the study protocol of a pilot study funded under the South-Central Mental Illness Research, Education, and Clinical Center pilot study program from the U.S. Department of Veterans Affairs. This randomized, open-label study was designed to evaluate the feasibility of completing a randomized trial of quetiapine vs. treatment as usual to promote patient engagement in PTSD patients with a history of m TBI.Discussion: We expect that the success of this ongoing study should provide us with the preliminary data necessary to design a full-scale randomized trial. Positive efficacy results in a full-scale trial should inform new VA guidelines for clinical practice by showing that quetiapine-related improvements in patient engagement and retention may be the most effective approach to assure that VA resources achieve the best possible outcome for veterans.Trial registration: NCT04280965.

关键词： Quetiapine Trauma-focused psychotherapy Posttraumatic stress disorder mild traumatic brain injury Veterans

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White Matter Changes in Posttraumatic Stress Disorder Following mild traumatic brain injury： A Prospective Longitudinal Diffusion Tensor Imaging Study

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Chinese Medical Journal 2016年第9期129卷 1091-1099页

作者： Li Li Gang Sun Kai Liu Min Li BO Li Shao-Wen Qian Li-Li Yu Institute of Postgraduates The Second Military Medical University Shanghai 200032 China Department of Medical Imaging Jinan Military General Hospital Jinan Shandong 250031 China Department of Statistics~ Ji'nan Military General Hospitail Jinan Sh'andong 2500311 China

Background： The ability to predict posttraumatic stress disorder （PTSD） is a critical issue in the management of patients with mild traumatic brain injury （mTBI）, as early medical and rehabilitative interventions may reduce the risks of long-term cognitive changes. The aim of the present study was to investigate how diffusion tensor imaging （DTI） metrics changed in the transition from acute to chronic phases in patients with mTBI and whether the alteration relates to the development of PTSD. Methods： Forty-three patients with mTBI and 22 healthy volunteers were investigated. The patients were divided into two groups： successful recovery （SR, n = 22） and poor recovery （PR, n = 21）, based on neurocognitive evaluation at 1 or 6 months after injury. All patients underwent magnetic resonance imaging investigation at acute （within 3 days）, subacute （10-20 days）, and chronic （1-6 months） phases after injury. Group differences of fractional anisotropy （FA） and mean diffusivity （MD） were analyzed using tract-based spatial statistics （TBSS）. The accuracy of DTI metrics for classifying PTSD was estimated using Bayesian discrimination analysis. Results： TBSS showed white matter （WM） abnormalities in various brain regions. In the acute phase, FA values were higher for PR and SR patients than controls （all P 〈 0.05）. In subacute phase, PR patients have higher mean MD than SR and controls （all P 〈 0.05）. In the chronic phase, lower FA and higher MD were observed in PR compared with both SR and control groups （all P 〈 0.05）. PR and SR groups could be discriminated with a sensitivity of 73%, specificity of 78%, and accuracy of 75.56%, in terms of MD value in subacute phase. Conclusions： Patients with mTBI have multiple abnormalities in various WM regions. DTI metrics change over time and provide a potential indicator at subacute stage for PTSD following mTBI.

关键词： Diffusion Tensor Imaging mild traumatic brain injury Posttraumatic Stress Disorder Tract-based Spatial Statistics

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Pulsed arterial spin labeling effectively and dynamically observes changes in cerebral blood flow after mild traumatic brain injury

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Neural Regeneration Research 2016年第2期11卷 257-261页

作者： Shu-ping Peng Yi-ning Li Jun Liu Zhi-yuan Wang Zi-shu Zhang Shun-ke Zhou Fang-xu Tao Zhi-xue Zhang Department of Radiology Second Xiangya Hospital Central South University Changsha Hunan Province China Hunan Cancer Hospital Changsha Hunan Province China

Cerebral blood flow is strongly associated with brain function, and is the main symptom and diagnostic basis for a variety of encephalopathies. However, changes in cerebral blood flow after mild traumatic brain injury remain poorly understood. This study sought to observe changes in cerebral blood flow in different regions after mild traumatic brain injury using pulsed arterial spin labeling. Our results demonstrate maximal cerebral blood flow in gray matter and minimal in the white matter of patients with mild traumatic brain injury. At the acute and subacute stages, cerebral blood flow was reduced in the occipital lobe, parietal lobe, central region, subcutaneous region, and frontal lobe. Cerebral blood flow was restored at the chronic stage. At the acute, subacute, and chronic stages, changes in cerebral blood flow were not apparent in the insula. Cerebral blood flow in the temporal lobe and limbic lobe diminished at the acute and subacute stages, but was restored at the chronic stage. These findings suggest that pulsed arterial spin labeling can precisely measure cerebral blood flow in various brain regions, and may play a reference role in evaluating a patient＇s condition and judging prognosis after traumatic brain injury.

关键词： nerve regeneration MRI pulsed arterial spin labeling technique cerebral blood flow mild traumatic brain injury GlasgowComa Scale white matter gray matter CT neural regeneration

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Application of diffusion kurtosis imaging technology in evaluating early mild traumatic brain injury

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TMR Integrative Medicine 2020年第11期4卷 1-7页

作者： Zhi-jie Zhang Wei Liu Guo-shi LV Zheng Pan Xiao-min Liu Bo Wang Medical Imaging Department of the Hospital of PLA 81st Group Army Zhangjiakou 075000China Radiology Department of Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical SciencesTianJin 300020China.

Objective To explore the value of magnetic resonance diffusion kurtosis imaging in diagnosing early tiny changes of brain tissue after mild traumatic brain injury.Methods A total of 22 patients with mild traumatic brain injury(study group)and 20 healthy subjects(control group)were enrolled in this study,and diffusion kurtosis imaging magnetic resonance scanning was employed in all subjects.fractional anisotropy,fractional anisotropy of kurtosis,mean kurtosis,axial kurtosis and radial kurtosis of diffusion kurtosis imaging parameters in the genu of corpus callosum,splenium corporis callosi,internal capsule,thalamus,putamen,cortex of frontal lobe,temporal lobe and parietal lobe at control group,the injured side and the mirror regions were measured,and the results were compared between the two groups.The receiver operating characteristic curve was used to evaluate the ability of different parameters in diagnosing mild traumatic brain injury.Results Compared with the control group,in the study group fractional anisotropy values of bilateral genu of corpus callosum,splenium corporis callosi,internal capsule and thalamus were significantly reduced,and fractional anisotropy of kurtosis values of bilateral thalamus and putamen were significantly reduced,and the differences were statistically significant(Pmild traumatic brain injury patients,which provide more imaging evidence for the clinical early diagnosis treatment and prognosis.

关键词： mild traumatic brain injury Magnetic resonance imaging Diffusion kurtosis imaging

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Post-Concussion Syndrome after a mild traumatic brain injury: A Minefield for Clinical Practice

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Journal of Behavioral and brain Science 2016年第6期6卷 227-232页

作者： Deborah L. Snell A. D. Sandy Macleod Tim Anderson Department of Orthopaedic Surgery and Musculoskeletal Medicine University of Otago Christchurch New Zealand Concussion Clinic Brain Injury Rehabilitation Service Burwood Hospital Christchurch New Zealand New Zealand brain Research Institute Christchurch New Zealand Department of Medicine University of Otago Christchurch New Zealand

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.

关键词： Post-Concussion Syndrome mild traumatic brain injury MTBI Chronic injury Symptoms

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The value of neurocognitive testing for acute outcomes after mild traumatic brain injury

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Military Medical Research 2015年第3期3卷 123-132页

作者： Latha Ganti Yasamin Daneshvar Sarah Ayala Pratik Shashikant Patel Aakash N.Bodhit Keith R.Peters Orlando Veterans Affairs Medical Center

Background: Traditionally, neurocognitive testing is performed weeks to months after head injury and is mostly performed on patients who continue to have symptoms or difficulties. In this study, we sought to determine whether these tests, when administered acutely, could assist in predicting short-term outcomes after acute traumatic brain injury(TBI).Methods: This is an IRB-approved prospective study of adult patients who came to the emergency department of our Level-1 trauma center with TBI. Patients were enrolled prospectively after providing written informed consent and underwent three separate neurocognitive tests: the Galveston Orientation Amnesia Test(GOAT), the Rivermead PostConcussion Survey Questionnaire(RPCSQ), and the Mini Mental Status Examination(MMSE).Results: A lower GOAT score was significantly associated with hospitalization(P=0.0212) and the development of post-concussion syndrome(PCS) at late follow-up(P=0.0081). A higher RPCSQ score was significantly associated with hospital admission(P=0.0098), re-admission within 30 days of discharge(P=0.0431) and evidence of PCS at early follow-up(P=0.0004). A higher MMSE score was significantly associated with not being admitted to the hospital(P=0.0002) and not returning to the emergency department(ED) within 72 hours of discharge(P=0.0078). Lower MMSE was also significantly associated with bleeding or a fracture on the brain CT(P=0.0431).Conclusions: While neurocognitive testing is not commonly performed in the ED in the setting of acute head injury, it is both feasible and appears to have value in predicting hospital admission and PCS. These data are especially important in terms of helping patients understand what to expect, thus, aiding in their recovery.

关键词： Neurocognitive testing mild traumatic brain injury Treatment outcome

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