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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of neurological surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Encephalic hemodynamic phases in subarachnoid hemorrhage:how to improve the protective effect in patient prognoses

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Neural Regeneration Research 2015年第5期10卷 748-752页

作者： Marcelo de Lima Oliveira Daniel Silva de Azevedo Milena Krajnyk de Azevedo Ricardo de Carvalho Nogueira Manoel Jacobsen Teixeira Edson Bor-Seng-Shu division of neurological surgery Hospital das ClinicasSchool of MedicineUniversity of Sao Paulo

Subarachnoid hemorrhage is frequently associated with poor prognoses. Three different hemo- dynamic phases were identified during subarachnoid hemorrhage： oligemia, hyperemia, and vasospasm. Each phase is associated with brain metabolic changes. In this review, we correlated the hemodynamic phases with brain metabolism and potential treatment options in the hopes of improving patient prognoses.

关键词： hemodynamic phases cerebral subarachnoid hemorrhage metabolic crises

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Advances in the imaging of cerebral aneurysm inflammation

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Neuroimmunology and Neuroinflammation 2015年第1期2卷 51-54页

作者： Michael R.Levitt M.Yashar S.Kalani Karam Moon Cameron G.McDougall Felipe C.Albuquerque division of neurological surgery Barrow Neurological InstituteSt.Joseph’s Hospital and Medical CenterPhoenixAZ 85013USA

Cerebral aneurysm formation,growth and rupture are thought to be the result of a complex interaction between cerebrovascular hemodynamics and ***,new evidence has emerged regarding the role of inflammation in the walls of cerebral *** methods to characterize the degree of inflammation in aneurysms could enable clinicians to estimate the risk of future aneurysm growth and rupture,influencing *** review examines emerging techniques of imaging inflammatory biomarkers in cerebral aneurysms.

关键词： Ferrosoferric oxide inflammation intracranial aneurysm magnetic resonance angiography subarachnoid hemorrhage

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Research in spinal surgery: Evaluation and practice of evidence-based medicine

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World Journal of Orthopedics 2014年第2期5卷 89-93页

作者： Mark E Oppenlander Christopher M Maulucci George M Ghobrial James S Harrop Department of neurological surgery Thomas Jefferson University Hospital Philadelphia PA19107 United States division of neurological surgery Barrow Neurological Institute St. Joseph Hospital and Medical CenterPhoenix AZ 85003 United States

Evidence-based medicine(EBM) is a common concept among medical practitioners, yet unique challenges arise when EBM is applied to spinal surgery. Due to the relative rarity of certain spinal disorders, and a lack of management equipoise, randomized controlled trials may be difficult to execute. Despite this, responsibility rests with spinal surgeons to design high quality studies in order to justify certain treatment modalities. The authors therefore review the tenets of implementing evidencebased research, through the lens of spinal disorders. The process of EBM begins with asking the correct *** appropriate study is then designed based on the research question. Understanding study designs allows the spinal surgeon to assess the level of evidence *** outcome measurements allow clinicians to communicate the success of treatment strategies, and will increase the quality of a given study design. Importantly,one must recognize that the randomized controlled trial is not always the optimal study design for a given research question. Rather, prospective observational cohort studies may be more appropriate in certain circumstances, and would provide superior generalizability. Despite the challenges involved with EBM, it is the future of medicine. These issues surrounding EBM are important for spinal surgeons, as well as health policy makers and editorial boards, to have familiarity.

关键词： Evidence-based medicine Spinal surgery Trial design Research Methodology

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Repositioning again of zonisamide for nerve regeneration

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Neural Regeneration Research 2016年第4期11卷 541-542页

作者： Kinji Ohno Hideki Yagi Bisei Ohkawara division of Neurogenetics Center for Neurological Diseases and CancerNagoya University Graduate School of Medicine Department of Orthopedic surgery Nagoya University Graduate School of Medicine

Drug repositioning is a strategy to identify a new application of a pre-approved drug,of which optimal dosage,administration routes,adverse effects,and contraindications are well *** repositioning enables fast and cost-effective application of an identified drug in clinical settings,and is especially suitable for orphan diseases,in which the number of patients is limited（Bernard,2014）.

关键词： Repositioning again zonisamide regeneration

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Can cinnamon bring aroma in Parkinson's disease treatment?

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Neural Regeneration Research 2015年第1期10卷 30-32页

作者： Priyanka Pahan Kalipada Pahan Department of neurological Sciences Division of NeuroscienceRush University Medical Center

While in one hand, due to genetic alterations, lifestyle changes, infections or injuries, or sudden turn of life events, we get health problems, on the other, we have been endowed with enormous natural remedies to take care our health. Cinnamon, the brown bark of cinna- mon tree, is one such natural product that has already been being used for centuries throughout the world as spice or flavoring agent. In addition, medieval physicians used cinnamon for medical purposes to treat a variety of disorders including arthritis, coughing, hoarseness, sore throats, etc. It was once so highly-prized that several wars were fought over it.

关键词： MPTP Can cinnamon bring aroma in Parkinson’s disease treatment

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Endoplasmic reticulum stress-induced apoptosis in the penumbra aggravates secondary damage in rats with traumatic brain injury

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Neural Regeneration Research 2016年第8期11卷 1260-1266页

作者： Guo-zhu Sun Fen-fei Gao Zong-mao Zhao Hai Sun Wei Xu Li-wei Wu Yong-chang He Department of Neurosurgery Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Department of Pharmacology Shantou University Medical CollegeShantouGuangdong ProvinceChina division of neurological surgery Barrow Neurological InstituteSt Joseph's Hospital and Medical CenterPhoenixAZUSA

Neuronal apoptosis is mediated by intrinsic and extrinsic signaling pathways such as the membrane-mediated,mitochondrial,and endoplasmic reticulum stress *** studies have examined the endoplasmic reticulum-mediated apoptosis pathway in the penumbra after traumatic brain injury,and it remains unclear whether endoplasmic reticulum stress can activate the caspase-12-dependent apoptotic pathway in the traumatic ***,we established rat models of fluid percussion-induced traumatic brain injury and found that protein expression of caspase-12,caspase-3 and the endoplasmic reticulum stress marker 78 k Da glucose-regulated protein increased in the traumatic penumbra 6 hours after injury and peaked at 24 ***,numbers of terminal deoxynucleotidyl transferase-mediated d UTP nick end labeling-positive cells in the traumatic penumbra also reached peak levels 24 hours after *** findings suggest that caspase-12-mediated endoplasmic reticulum-related apoptosis is activated in the traumatic penumbra,and may play an important role in the pathophysiology of secondary brain injury.

关键词： nerve regeneration endoplasmic reticulum stress apoptosis caspase-12 caspase-3 traumatic penumbra traumatic brain injury neural regeneration

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Elevated fibrinogen plasma level is not an independent predictor of poor prognosis in a large cohort of Western patients undergoing surgery for colorectal cancer

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World Journal of Gastroenterology 2016年第45期22卷 9994-10001页

作者： Corrado Pedrazzani Guido Mantovani Gian Luca Salvagno Elisabeth Baldiotti Andrea Ruzzenente Calogero Iacono Giuseppe Lippi Alfredo Guglielmi division of General and Hepatobiliary surgery Department of Surgical Sciences Dentistry Gynecology and Pediatrics University of Verona Section of Clinical Biochemistry Department of Neurological Biomedical and Movement Sciences University of Verona

AIM To evaluate the clinical significance of the preoperative fibrinogen plasma level as a prognostic marker after surgery for colorectal *** This retrospective study analysed 652 patients undergoing surgery for stage Ⅰ-Ⅳ colorectal cancer between January 2005 and December 2012, at the division of General surgery A, University of Verona Hospital Trust, in whom preoperative fibrinogen plasma values were assessed at baseline. Fibrinogen is involved in tumourigenesis as well as tumour progression in several malignancies. Correlations between preoperative plasma fibrinogen values and clinicopathological characteristics were investigated. Univariate and multivariate survival analyses were performed to identify factors associated with overall and tumour-related *** Among the 652 patients, the fibrinogen value was higher than the threshold of 400 mg/dL in 345 patients(53%). The preoperative mean ± SD of fibrinogen was 426.2 ± 23.2 mg/dL(median: 409 mg/dL; range: 143-1045 mg/d L). Preoperative fibrinogen values correlated with age(P = 0.003), completeness of tumour resection, potentially curative vs palliative(P surgery.

关键词： Colorectal cancer Fibrinogen Tumour markers Prognosis Colorectal surgery

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An update on spinal cord injury research

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Neuroscience Bulletin 2013年第1期29卷 94-102页

作者： He-Qi Cao Er-Dan Dong division of neurological Disorders and Mental Health Department of Health Sciences National Natural Science Foundation of China

Spinal cord injury （SCI） can have a range of debilitating effects and permanently alter the capabilities and quality of life of survivors. The first specialized centers of care for SCI were established in 1944 and since then an increasing amount of research has been carried out in this area. Despite this, the present treatment and care levels for SCI are not comparable to those in other areas of medicine. In the clinic, the aim of SCI treatment is primarily to limit secondary damage by reducing compression in trauma spots and stabilizing the spinal column. Currently, no effective strategy for functional recovery is offered. In this review, we focus on research progress on the molecular mechanisms underlying SCI, and assess the treatment outcomes of SCI in animal models, i.e., neurotrophins and stem cells are discussed as pre-clinical therapies in animal models. We also assess the resources available and national research projects carried out on SCI in China in recent years, as well as making recommendations for the future allocation of funds in this area.

关键词： spinal cord injury neurotrophins stem cell-based transplantation research funding

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Trans-synaptic degeneration as a mechanism of neurodegeneration in multiple sclerosis

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Neural Regeneration Research 2023年第12期18卷 2682-2684页

作者： Olwen C.Murphy Peter A.Calabresi Shiv Saidha division of Neuroimmunology and neurological Infections Department of NeurologyJohns Hopkins UniversityBaltimoreMDUSA

Multiple sclerosis(MS) is regarded as an immunemediated,demyelinating disorder of the central nervous system,however neuroaxonal degeneration is accepted as the principal substrate of disability accumulation(Dutta and... 详细信息

关键词： degeneration sclerosis myelin

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