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Simple procedure for assessing diffuse subarachnoid hemorrhage successfully created using filament perforation method in mice

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Animal Models and Experimental Medicine 2024年第1期7卷 77-81页

作者： Tatsushi Mutoh Ryota Tochinai Hiroaki Aono Masayoshi Kuwahara Yasuyuki Taki Tatsuya Ishikawa Department of Surgical Neurology Research Institute for Brain and Blood VesselsAkita Cerebrospinal and Cardiovascular CenterAkitaJapan Department of Aging Research and Geriatric Medicine Institute of DevelopmentAging and CancerTohoku UniversitySendaiJapan Department of Veterinary Pathophysiology and Animal Health Graduate School of Agriculture and Life SciencesThe University of TokyoTokyoJapan

The murine model of subarachnoid hemorrhage(SAH)is a valuable experimental tool for investigating molecular and cellular mechanisms,and the endovascular filament perforation technique can be used to simulate prominent pathophysiological features observed after human SAH;however,current validation methods for assessing an appropriate SAH model are ***,we introduce a simple procedure for se-lecting a mouse model of diffuse *** was induced in 24 mice using a standard filament perforation *** confirming survival at 24 h,SAH was scored 0-1 based on T2*-weighted images on whole-brain magnetic resonance imaging(MRI)and visual surveillance of the cisterna magna(CM)through the dura *** CM-based SAH grading correlated well with a reference parameter defined by extracted brain(r^(2)=0.53,p<0.0001).The receiver operating characteristic curve revealed a sensi-tivity of 85%and a specificity of 91%for detecting diffuse SAH,with a similar area under the curve(0.89±0.06[standard error of the mean])as the MRI-based grading(0.72±0.10,p=0.12).Our data suggest that confirming an SAH clot in the CM is a valuable way to select a clinically relevant diffuse SAH model that can be used in future experimental studies.

关键词： cisterna magna clot distribution filament perforation mouse model subarachnoid hemorrhage

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Measurement of the Wheelchair-Operating Time Spent by Stroke Patients Using a New Triaxial Accelerometer System

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Open Journal of Therapy and Rehabilitation 2014年第4期2卷 147-155页

作者： Yoshino Terui Takanobu Shioya Koichi Hasegawa Eriko Suto Atsuyoshi Kawagoshi Masahiro Satake Sachie Sawamura Shunichi Sakata Department of Physical Therapy Akita University Graduate School of Health Sciences Akita Japan akita Prefectural Center for Rehabilitation and Psychiatric Medicine Akita Japan akita City General Hospital Akita Japan brain and blood vessels-akita Akita Japan Kumamoto Technology and Industry Foundations Kumamoto Japan

Purpose: We investigated the validity of a triaxial accelerometer system for measuring the time spent lying down, sitting, standing, walking, and operating a wheelchair by control subjects and stroke patients in a convalescence ward. Methods: Physical activities were measured using a new triaxial accelerometer system (A-MES;Activity Monitoring and Evaluation System) that consists of two sensors, a station, and analytical software used with a personal computer. In Experiment 1, the times that the healthy subjects (n = 12) spent operating a wheelchair, lying down, sitting, standing, and walking were measured both by the A-MES and by videotaping (video time). In Experiment 2, the amounts of time spent by the stroke patients not able to walk without support (n = 30) as they were lying down, sitting, standing, walking, and operating a wheelchair were measured by the A-MES. Results: The time spent operating a wheelchair measured with the A-MES was significantly correlated with the video time in the healthy subjects. The stroke patients’ average times (minutes) of total, operating a wheelchair, lying down, sitting, standing, and walking were 601.0 ± 18.1, 57.1 ± 28.8, 265.0 ± 86.3, 263.3 ± 60.6, 7.8 ± 7.0, and 7.7 ± 6.0, respectively. Conclusions: The A-MES accurately evaluated the stroke patients’ time spent operating a wheelchair. The stroke patients’ mean time spent operating a wheelchair over the course of one day was 57.1 ± 28.8 min in a Center for Rehabilitation.

关键词： Stroke Wheelchairs Physical Activity

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Cisplatin Inhibits AhR Activation

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American Journal of Molecular Biology 2018年第1期8卷 69-82页

作者： Erina Sasaki-Kudoh Ikuru Kudo Yuka Kakizaki Miki Hosaka Shun-Ichi Ikeda Seiya Uemura Ewa Grave Shuntaro Togashi Taku Sugawara Hiroaki Shimizu Hideaki Itoh Department of Neurosurgery Akita University Graduate School of Medicine Akita Japan Department of Life Science Akita University Graduate School of Engineering Science Akita Japan Department of Spinal Cord and Spine Surgery Research Institute for Brain and Blood Vessels-Akita Akita Japan

The AhR binds to contain ligands, such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, 3-methylcholantrene, or β-naphthoflavone. The activation mechanism of AhR is not yet fully understood, but it is known that AhR associates with the molecular chaperone HSP90 in the cytoplasm. There are a few reports about the association or dissociation of AhR and HSP90, and which domain of HSP90 binds to AhR. We reported the association and activation mechanisms between HSP90 and AhR-PAS or AhR-bHLH. In the current study, we found that cisplatin inhibits the AhR activation. Although ATP and 17-DMAG have no effect on the dissociation of HSP90 from AhR, some contents of HSP90 were dissociated from AhR in the presence of cisplatin. We could detect the increase of CYP1A in the presence of 3-MC. On the contrary, the induction of CYP1A1 was inhibited in the presence of cisplatin. We couldn’t detect AhR in the HeLa cell soluble fraction in the presence of 50 μM cisplatin. In the presence of MG-132, we could detect AhR. These results suggested that AhR was dissociated from the HSP90 chaperone complex and processed during the protein proteasome degradation system in the presence of cisplatin.

关键词： Cisplatin CDDP AhR Aryl Hydrocarbon Receptor HSP90 17-DMAG

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Progress of research in the application of ultrasound technology for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2823-2837页

作者： Qiuquan Cai Lianghui Meng Meina Quan Ling Wang Jing Ren Chenguang Zheng Jiajia Yang Dong Ming Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Innovation Center for Neurological Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina brain-Computer Interaction and Human-Machine Fusion Haihe Laboratory Tianjin UniversityTianjinChina Tianjin Key Laboratory of brain Science and Neural Engineering Tianjin UniversityTianjinChina

Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive *** presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer’s *** use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent *** a safe and feasible therapeutic and drug-delivery method,ultrasound has shown promise in improving cognitive *** article provides a summary of the application of ultrasound technology for treating Alzheimer’s disease over the past 5 years,including standalone ultrasound treatment,ultrasound combined with microbubbles or drug therapy,and magnetic resonance imaging-guided focused ultrasound *** is placed on the benefits of introducing these treatment methods and their potential *** found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-βplaque *** believe that ultrasound is an effective therapy for Alzheimer’s disease,and this review provides a theoretical basis for future ultrasound treatment methods.

关键词： Alzheimer’s disease blood-brain barrier drugs magnetic resonance imaging-guided focused ultrasound microbubbles scanning ultrasound ultrasound ultrasound stimulation

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Fibrinogen’s potential role in connecting cerebrovascular abnormalities with glymphatic dysfunction in Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 203-204页

作者： Vishal Singh Arnab Choudhury Hyung Jin Ahn Department of Pharmacology Physiology and NeurosciencesRutgers-New Jersey Medical SchoolNewarkNJUSA brain Health Institute Rutgers UniversityPiscatawayNJUSA

Alzheimer’s disease(AD)stands out as the primary manifestation of age-related dementia,portraying a chronic neurodegenerative disorder distinguished by the accumulation of fibrillar amyloid-β(Aβ)plaques and neurofibrillary tangles of hyperphosphorylated ***,from a clinical standpoint,AD presents itself as a complex condition with a spectrum of dysfunctions rather than a singular pathological *** often-overlooked aspect of the disease is the presence of extensive cerebrovascular abnormalities,given that the majority of AD patients experience altered cerebral blood flow,damaged vasculature,increased microinfarcts and *** models of AD further support this observation,showing cerebrovascular dysfunction such as impaired cerebral blood flow and altered cerebrovascular reactivity(Tataryn et al.,2021;Gareau et al.,2023).

关键词： cerebrovascular dysfunction Alzheimer

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Gamma oscillations and their role in orchestrating balance and communication following stroke

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Neural Regeneration Research 2025年第2期20卷 477-478页

作者： Montana Samantzis Cong Wang Matilde Balbi Queensland brain Institute The University of QueenslandBrisbaneQLDAustralia Engineering Research Centre of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina

Induced brain oscillations in the gamma range have recently garnered attention due to their reported neuroprotective effects in the treatment of Alzheimer’s *** method differs from pharmacological approaches by tapping into the neuronal population dynamics that underlie the homeostatic processes in the brain that are crucial for the recovery of ***,induced gamma-range oscillations have been used to improve cerebral blood flow,motor function,and synaptic plasticity in a mouse model of focal stroke,highlighting the broad potential of recruiting intrinsic recovery processes for the treatment of neurological *** open questions,such as the frequency specificity of the benefits,will shed light on the intrinsic processes involved and allow clinicians to optimize recovery after stroke.

关键词： protective specificity Alzheimer

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Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1599-1612页

作者： Guibo Qi Han Tang Jianian Hu Siying Kang Song Qin Department of Anatomy Histologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for brain Science Fudan UniversityShanghaiChina

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier ***, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could pro

关键词： Alzheimer's disease blood–brain barrier ependymoglial cells hypothalamus metabolic diseases neural stem cells neurogenesis neuroinflammatory diseases neurons tanycyte

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The role of peptidase neurolysin in neuroprotection and neural repair after stroke

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Neural Regeneration Research 2021年第1期16卷 21-25页

作者： Vardan T.Karamyan Department of Pharmaceutical Sciences and Center for blood brain Barrier Research School of PharmacyTTUHSCAmarilloTXUSA

Current experimental stroke research has evolved to focus on detailed understanding of the brain’s self-protective and restorative mechanisms,and harness this knowledge for development of new *** this context,the role of peptidases and neuropeptides is of growing *** this focused review,peptidase neurolysin(Nln)and its extracellular peptide substrates are briefly discussed in relation to pathophysiology of ischemic *** of Nln following stroke is viewed as a compensatory cerebroprotective mechanism in the acute phase of stroke,because the main neuropeptides inactivated by Nln are neuro/cerebrotoxic(bradykinin,substance P,neurotensin,angiotensin II,hemopressin),whereas the peptides generated by Nln are neuro/cerebroprotective(angiotensin-(1–7),Leu-/Met-enkephalins).This notion is confirmed by experimental studies documenting aggravation of stroke outcomes in mice after inhibition of Nln following stroke,and dramatic improvement of stroke outcomes in mice overexpressing Nln in the *** role of Nln in the(sub)chronic phase of stroke is less clear and it is likely,that this peptidase does not have a major role in neural repair *** is because,the substrates of Nln are less uniform in modulating neurorestorative mechanisms in one direction,some appearing to have neural repair enhancing/stimulating potential,whereas others doing the *** studies focusing on the role of Nln in pathophysiology of stroke should determine its potential as a cerebroprotective target for stroke therapy,because its unique ability to modulate multiple neuropeptide systems critically involved in brain injury mechanisms is likely advantageous over modulation of one pathogenic pathway for stroke pharmacotherapy.

关键词： compensatory cerebroprotection drug target endogenous neuroprotective mechanism neuropeptide neurorestoration peptidase

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blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第9期20卷 2556-2570页

作者： Yongting Lv Hongfu Li Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Department of Medical Genetics and Center for Rare disease Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Nanhu brain-Computer Interface Institute HangzhouZhejiang Province

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely *** principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial *** biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even *** these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and *** light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and ***,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal *** fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration *** DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related *** is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease *** the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable *** review summarizes the lat

关键词： amyotrophic lateral sclerosis biomarker blood biomarkers diagnosis glial fibrillary acidic protein neurofilament light chain prognosis TAR DNA-binding protein 43

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Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural Regeneration Research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha J.Holdsworth Alistair J.Gunn Laura Bennet Hamid Abbasi Mātai Medical Research Institute Tairāwhiti GisborneNew Zealand Department of Anatomy&Medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for brain Research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

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