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Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez Daniel Refai Gerald R.Rodts Christian Mustroph David Gimbel Jonathan Grossberg Daniel l.Barrow Matthew F.Gary Ali M.Alawieh department of neurosurgery Emory University School of MedicineAtlantaGAUSA department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

Effect of type-2 astrocytes on the viability of dorsal root ganglion neurons and length of neuronal processes

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Neural Regeneration Research 2014年第2期9卷 119-128页

作者： Chunling Fan Hui Wang Dan Chen Xiaoxin Cheng Kun Xiong Xuegang luo Qilin Cao department of Human Anatomy and Neurobiology Xiangya School of MedicineCentral South University The vivian l smith department of neurosurgery UT Medical School at Houston

The role of type-2 astrocytes in the repair of central nervous system injury remains poorly un- derstood. In this study, using a relatively simple culture condition in vitro, type-2 astrocytes, differentiated from oligodendrocyte precursor cells by induction with bone morphogenetic pro- tein-4, were co-cultured with dorsal root ganglion neurons. We examined the effects of type-2 astrocytes differentiated from oligodendrocyte precursor cells on the survival and growth of dorsal root ganglion neurons. Results demonstrated that the number of dorsal root ganglion neurons was higher following co-culture of oligodendrocyte precursor cells and type-2 astrocytes than when cultured alone, but lower than that of neurons co-cultured with type-1 astrocytes. The length of the longest process and the length of all processes of a single neuron were shortest in neurons cultured alone, followed by neurons co-cultured with type-2 astroc^es, then neurons co-cultured with oligodendrocyte precursor cells, and longest in neurons co-cultured with type-1 astrocytes. These results indicate that co-culture with type-2 astrocytes can increase neuronal survival rate and process length. However, compared with type-1 astrocytes and oligodendrocyte precursor cells, the promotion effects of type-2 astrocytes on the growth of dorsal root ganglion neurons were weaker.

关键词： nerve regeneration spinal cord injury oligodendrocyte oligodendrocyte precursor cells astrocytes bone morphogenetic protein neurons neurites dorsal root ganglion NIH grant neuralregeneration

The concentration game: differential effects of bioactive signaling in 2D and3D culture

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Neural Regeneration Research 2016年第1期11卷 66-68页

作者： laura A.smith Callahan The vivian l.smith department of neurosurgery & Center for Stem Cell and Regenerative Medicine University of Texas Health Science Center at Houston

Traumatic injuries to the central nervous system,such as traumatic brain injury,spinal cord injury and stroke,have a high prevalence,enormous financial costs and lack clinical treatments that restore neurological function（Ma et al.,2014）These injuries trigger a series of secondary biochemical and cellular responses that ultimately lead to cellular death and themaintenance of an unsupportive extracellular matrix （ECM） for tissue regeneration （Silva et al., 2014）. Artificial ECM or scaf- folds represent a way to alter this unsupportive environment to improve the efficacy of stem cell therapies and enhance neural tissue regeneration （Figure 1）.

关键词： bioactive injuries restore biochemical neurological traumatic signaling scaffold ultimately likely

Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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Neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： Victoria Jiménez Carretero IrisÁlvarez-Merz Jorge Hernández-Campano Sergei A.Kirov Jesús M.Hernández-Guijo department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain Ramón y Cajal Institute for Health Research(IRYCIS) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain Institute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany department of Neuroscience and Regenerative Medicine&department of neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(l-alanine,glycine,l-glutamine,and l-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate *** N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling N-methyl-D-aspartate receptor non-excitatory amino acids stroke synaptic transmission

The expression and functions of microRNAs in pancreatic adenocarcinoma and hepatocellular carcinoma

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Chinese Journal of Cancer 2011年第8期30卷 540-550页

作者： Wei li Drake G. leBrun Min li College of Medicine Shandong University of Traditional Chinese Medicine Jinan Shandong 250355 P. R. China The vivian l. smith department of neurosurgery the University of Texas Health Science Center at Houston Medical School Houston Texas 77030 USA.

Pancreatic adenocarcinoma and hepatocellular carcinoma are devastating human malignancies that are characterized by poor prognosis,late onset,and a lack of known *** diagnostic and therapeutic molecular targets are desperately needed to develop novel and effective treatment *** (miRNAs) are an emerging class of molecules with roles in various cellular processes,including growth,survival,and *** importantly,aberrant expression of miRNAs has been implicated in cancer *** expression profiles of pancreatic adenocarcinoma and hepatocellular carcinoma indicate selective overexpression of oncogenic miRNAs and down-regulation of tumor suppressive miRNAs in these *** review summarizes results from key studies conducted to characterize the miRNA expression profiles of pancreatic adenocarcinoma and hepatocellular carcinoma and describes the potential mechanisms by which some oncogenic or tumor suppressive miRNAs ***,this review outlines novel therapeutic strategies for targeting miRNAs.

关键词： microRNA 胰腺癌肝癌 miRNAs 小分子RNA 肿瘤抑制生物标志物恶性肿瘤

Flow diversion covering the M1 origin as a last resort

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Stroke & Vascular Neurology 2019年第3期4卷 141-147页

作者： li-Mei lin Matthew T Bender Geoffrey P Colby Bowen Jiang Jessica K Campos David A Zarrin Robert W C Young Risheng Xu Justin M Caplan Judy Huang Rafael J Tamargo Alexander l Coon department of neurosurgery University of California IrvineOrangeCaliforniaUSA department of neurosurgery Johns Hopkins University School of MedicineBaltimoreMarylandUSA department of neurosurgery University of California Los AngelesLos AngelesCaliforniaUSA

Introduction Internal carotid artery termination(ICAT)and proximal A1 aneurysms can be challenging for open surgical clipping or endovascular *** with flow diversion covering the middle cerebral artery(MCA),an end vessel supplying a terminal circulation,has not been *** A prospective,Institutional Review Board-approved database was analysed for patients with pipeline embolisation device(PED)placement from the anterior cerebral artery(ACA)to the ICA during cerebral aneurysm *** Nine cases were identified,including five proximal A1,three posterior communicating artery and one ICAT aneurysm *** aneurysm size was 8.3 mm(range 3-17),with 67%saccular and 78%*** indication for treatment was significant dome irregularity(44%),recurrence or enlargement(33%),underlying collagen vascular disorder(11%)and traumatic pseudoaneurysm(11%).Preservation of the ipsilateral ACA(with PED placed in A1)was performed when the anterior communicating artery(67%)or contralateral A1(33%)were absent on *** coiling was done in four cases(44%).There was one major stroke leading to mortality(11%)and one minor stroke(11%).Clinical follow-up was 27 months on ***-up digital subtraction angiography(average interval 15 months)showed complete aneurysm obliteration(88%)or dome occlusion with entry remnant(12%).The jailed MCA showed minimal or mild delay(primarily anterograde flow)in 75%of cases and significant delay(reliance primarily on ACA and external carotid artery collaterals)in 25%.Conclusions Covering the MCA with a flow diverting stent should be reserved for select rare *** attention to blood pressure augmentation during the periprocedural period is necessary to minimise potential ischaemic compromise.

关键词： primarily resort sided

Novel diamond shuttle to deliver flexible neural probe with reduced tissue compression

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Microsystems & Nanoengineering 2020年第1期6卷 903-915页

作者： Kyounghwan Na Zachariah J.Sperry Jiaao lu Mihaly Voroslakos Saman S.Parizi Tim M.Bruns Euisik Yoon John P.Seymour Electrical Engineering&Computer Science department University of MichiganAnn ArborMI 48105USA Biomedical Engineering department University of MichiganAnn ArborMI 48105USA Biointerfaces Institute University of MichiganAnn ArborMI 48105USA The Neuroscience Institute New York UniversityNew YorkNY 10016USA Center for Nanomedicine Institute for Basic Science(IBS)Seoul 03722Korea Graduate Program of Nano Biomedical Engineering(Nano BME) Yonsei-IBS InstituteYonsei UniversitySeoul 03722Korea vivian l smith department of neurosurgery University of Texas Health Science CenterHoustonTX 77030USA department of Electrical and Computer Engineering Rice UniversityHoustonTX 77005USA

The ability to deliver flexible biosensors through the toughest membranes of the central and peripheral nervous system is an important challenge in neuroscience and neural *** devices implanted through dura mater and thick epineurium would ideally create minimal compression and acute damage as they reach the neurons of *** demonstrate that a three-dimensional diamond shuttle can be easily made with a vertical support to deliver ultra-compliant polymer microelectrodes(4.5-µm thick)through dura mater and thick *** diamond shuttle has 54%less cross-sectional area than an equivalently stiff silicon shuttle,which we simulated will result in a 37%reduction in blood vessel *** also discovered that higher frequency oscillation of the shuttle(200Hz)significantly reduced tissue compression regardless of the insertion speed,while slow speeds also independently reduced tissue *** and recording performance are demonstrated in rat and feline models,but the large design space of these tools are suitable for research in a variety of animal models and nervous system targets.

关键词： sectional neural thick

Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury,both in vivo and in vitro

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Neural Regeneration Research 2018年第7期13卷 1204-1211页

作者： Pei-Dong Zheng Rajneesh Mungur Heng-Jun Zhou Muhammad Hassan Sheng-Nan Jiang Jie-Sheng Zheng department of neurosurgery the First Affiliated HospitalCollege of MedicineZhejiang University

Neural stem cells have great potential for the development of novel therapies for nervous system ***,the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central nervous system *** B has a robust neuroprotective *** this study,we investigated the cell and molecular mechanisms underlying the neuroprotective effect of ginkgolide B on focal cerebral ischemia/reperfusion injury in vitro and in *** stem cells were treated with 20,40 and 60 mg/l ginkgolide B in *** staining was used to assess cellular expression of neuron-specific enolase,glial fibrillary acid protein and suppressor of cytokine signaling *** treatment with 40 and 60 mg/l ginkgolide B,cells were large,with long ***,the proportions of neuron-specific enolase-,glial fibrillary acid protein-and suppressor of cytokine signaling 2-positive cells increased.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery *** hours after ischemia,ginkgolide B（20 mg/kg） was intraperitoneally injected,once a *** longa＇s method was used to assess neurological *** was performed to evaluate the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive ***-time quantitative polymerase chain reaction was used to measure m RNA expression of brain-derived neurotrophic factor and epidermal growth *** blot assay was used to analyze the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling *** B decreased the neurological deficit score,increased the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells,increased the m RNA expression of brain-derived neurotrophic factor and epidermal growth factor,and increased the expression levels of brain-derived neurotrophic factor and suppressor of cytokine sig

关键词： nerve regeneration brain-derived neurotrophic factor epidermal growth factor suppressor of cytokine signaling 2 neuron-specific enolase glial fibrillary acid protein nestin bromodeoxyuridine neurological function middle cerebral artery occlusion astrocytes neural regeneration

Procedural complexity independent of P2Y12 reaction unit(PRU)values is associated with acute in situ thrombosis in Pipeline flow diversion of cerebral aneurysms

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Stroke & Vascular Neurology 2018年第3期3卷 169-175页

作者： Bowen Jiang Matthew T Bender Erick M Westbroek Jessica K Campos li-Mei lin Risheng Xu Rafael J Tamargo Judy Huang Geoffrey P Colby Alexander l Coon department of neurosurgery Johns Hopkins University School of MedicineBaltimoreMarylandUSA department of neurosurgery University of CaliforniaIrvine School of MedicineOrangeCaliforniaUSA department of neurosurgery University of CaliforniaLos AngelesLos AngelesCaliforniaUSA

background Acute in situ thrombosis is an ischaemic phenomenon during Pipeline embolisation device(PED)procedures with potentially high morbidity and *** is controversy regarding the role of platelet function testing with P2Y12 assay as a predictor of intraprocedural thromboembolic *** is limited knowledge on whether procedural complexity influences these *** Data were collected retrospectively on 742 consecutive PED cases at a single *** with intraprocedural acute thrombosis were compared with patients without these *** A cohort of 37 PED cases with acute in situ thrombosis(mean age 53.8 years,mean aneurysm size 8.4 mm)was matched with a cohort of 705 PED cases without intraprocedural thromboembolic events(mean age 56.4 years,mean aneurysm size 6.9 mm).All patients with in situ thrombosis received intra-arterial and/or intravenous *** two groups were evenly matched in patient demographics,previous treatment/subarachnoid hemorrhage(SAH)and aneurysm *** was no statistical difference in postprocedural P2Y12 reaction unit(PRU)values between the two groups,with a mean of 156 in the in situ thrombosis group vs 148 in the control group(p=0.5894).Presence of cervical carotid tortuosity,high cavernous internal carotid artery grade,need for multiple PED and vasospasm were not significantly different between the two *** in situ thrombosis group had statistically significant longer fluoroscopy time(60.4 vs 38.4 min,pling(24.3% vs 8.37%,p=0.0010)and higher utilisation of balloon angioplasty(37.8% vs 12.2%,plinically,the in situ thrombosis cohort had higher incidence of major and minor stroke,intracerebral haemorrhage and length of *** Predictors of procedural complexity(higher radiation exposure,longer fluoroscopy time,adjunctive coiling and need for balloon angioplasty)are asso

关键词： P2Y12 matched balloon