Brain Research最新文献_第6页

Auditory research across time: Insights from an interdisciplinary publishing platform 跨越时间的听觉研究：来自跨学科出版平台的见解。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-11 DOI: 10.1016/j.brainres.2025.149453

Andréanne Sharp

引用次数: 0

Chronic traumatic brain injury induces neurodegeneration, neuroinflammation, and cognitive deficits in a T cell-dependent manner 慢性创伤性脑损伤以T细胞依赖的方式诱导神经变性、神经炎症和认知缺陷。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-10 DOI: 10.1016/j.brainres.2025.149446

Leyre Ayerra , Kirill Shumilov , Allen Ni , Maria S. Aymerich , Stuart H. Friess , Marta Celorrio

Traumatic brain injury (TBI) can lead to chronic neuroinflammation, and neurodegeneration associated with long-term cognitive deficits. Following TBI, the acute neuroinflammatory response involves microglial activation and the release of proinflammatory cytokines and chemokines which induce the recruitment of peripheral immune cells such as monocytes and ultimately T cells. Persistent innate and adaptive immune cell responses can lead to chronic neurodegeneration and functional deficits. Therefore, understanding the dynamic interaction between chronic immune responses and TBI-related pathogenesis and progression of the disease is crucial. We hypothesized that T cells have an essential role in TBI severity and recovery. We used generic T cell deletion mice (TCRβ^−/−δ^−/−) vs Wild-type mice that underwent controlled cortical impact assessing behavioral, histological, and immune system response outcomes at 3 months post-TBI. The absence of T cells reduced neurodegeneration and was associated with improved neurological outcomes 3 months post-injury. Furthermore, the absence of T cells enhanced an anti-inflammatory phenotype in peripheral myeloid cells in the injured brain. Collectively, these data indicate that T cells promote persistent neuropathology and functional impairments chronically after TBI.

创伤性脑损伤（TBI）可导致慢性神经炎症和与长期认知缺陷相关的神经变性。创伤性脑损伤后，急性神经炎症反应涉及小胶质细胞激活和促炎细胞因子和趋化因子的释放，诱导外周血免疫细胞（如单核细胞和最终的T细胞）的募集。持续的先天和适应性免疫细胞反应可导致慢性神经变性和功能缺陷。因此，了解慢性免疫反应与tbi相关的发病和进展之间的动态相互作用至关重要。我们假设T细胞在TBI的严重程度和恢复中起重要作用。我们使用通用T细胞缺失小鼠（TCRβ-/-δ-/-）与野生型小鼠进行对照，在tbi后3 个月评估行为、组织学和免疫系统反应结果。T细胞的缺失减少了神经退行性变，并与损伤后3 个月的神经预后改善有关。此外，T细胞的缺失增强了受损大脑中外周髓细胞的抗炎表型。总的来说，这些数据表明，T细胞在TBI后慢性促进持续的神经病理和功能损伤。

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引用次数: 0

Glymphatic system impairment in normal tension glaucoma evaluated by diffusion tensor image analysis along the perivascular space 沿血管周围空间扩散张量图像分析评价正常张力性青光眼的淋巴系统损害。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-08 DOI: 10.1016/j.brainres.2025.149450

Ting Li , Qian Wang , Bingbing Yang , Xiaoxia Qu , Weiwei Chen , Huaizhou Wang , Ningli Wang , Junfang Xian

Disruption of the glymphatic system plays a vital role in pathogenesis of neurodegeneration in normal tension glaucoma (NTG). We evaluated the impairment of glymphatic system of NTG patients by diffusion tensor image analysis along the perivascular space (DTI-ALPS), and explored the correlation between the ALPS index and dysfunction of visual cortices in resting state. DTI-ALPS was applied to 37 normal controls (NCs) and 37 NTG patients. Multidirectional diffusivity maps and fractional anisotropy (FA) maps were reconstructed to calculate ALPS index. The Amplitude of low-frequency fluctuation (ALFF) in visual cortices (V1-V5) were calculated using resting-state fMRI. Clinical data and ALPS indexes were compared between the groups. Lateralization of ALPS indexes and differences in visual field of two eyes were analyzed. Subsequently, regression analyses between ALPS indexes and mean deviation (MD) values of bilateral eyes and ALFF of visual cortices were performed. The bilateral ALPS indexes of NTG patients decreased significantly. In NCs and NTG patients, ALPS indexes in right hemisphere were lower than that in left hemisphere. The right ALPS indexes of NTG patients were positively correlated with the MD values of the left eyes. In NTG patients, decreased ALFF was detected in right V1 and bilateral V2-5, and the left ALPS indexes were positively correlated with ALFF in bilateral V1, V2, V5, and right V3V area. The ALPS index decreased in NTG patients, correlated with visual defects and ALFF, indicating impairment of the glymphatic system and the potential to be a biomarker in the future.

淋巴系统的破坏在正常张力性青光眼（NTG）神经变性的发病机制中起着至关重要的作用。我们采用沿血管周围间隙弥散张量图像分析（DTI-ALPS）评估NTG患者淋巴系统的损害，并探讨静息状态下ALPS指数与视觉皮质功能障碍的相关性。DTI-ALPS应用于37例正常对照和37例NTG患者。重建多向扩散系数图和分数各向异性（FA）图，计算ALPS指数。静息状态fMRI计算视觉皮层（V1-V5）低频波动幅度（ALFF）。比较两组患者的临床资料及ALPS指标。分析两眼ALPS指数的偏侧及视野差异。随后，对ALPS指数与双侧眼平均偏差（MD）值和视觉皮层ALFF值进行回归分析。NTG患者双侧ALPS指数明显下降。NCs和NTG患者右半球ALPS指数低于左半球。NTG患者右眼ALPS指数与左眼MD值呈正相关。NTG患者右侧V1、双侧V2-5区ALFF降低，左侧ALPS指数与双侧V1、V2、V5、右侧V3V区ALFF呈正相关。NTG患者的ALPS指数下降，与视觉缺陷和ALFF相关，提示淋巴系统受损，未来可能成为一种生物标志物。

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引用次数: 0

Astragaloside IV promotes neuronal axon regeneration by inhibiting the PTEN/AKT pathway 黄芪甲苷通过抑制PTEN/AKT通路促进神经元轴突再生。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-08 DOI: 10.1016/j.brainres.2025.149451

Luning Lin , Chenyang Zhao , Huijuan Lv , Liangrong Zhu , Wangen Wang , Xintian Zheng

Background

Neuronal survival and regeneration are critical aspects of recovery from ischemic brain injuries. Astragaloside IV (AS-IV), a saponin extracted from the traditional Chinese medicine Astragalus membranaceus, has shown promise in promoting neuronal health. This study investigates the effects of AS-IV on neuronal survival and apoptosis post-oxygen-glucose deprivation (OGD), focusing on the modulation of the PTEN/AKT signaling pathway.

Methods

Rat primary neuronal cells were isolated and subjected to OGD to simulate ischemic conditions. Afterwards, cells were treated with low and high doses of AS-IV. Neuronal viability and apoptosis were assessed using MTT and flow cytometry (FCM) assays. Immunofluorescence and Western blot analyses were performed to evaluate the expression of neuronal markers and proteins involved in the PTEN/AKT pathway.

Results

Post-OGD, neuronal cells exhibited decreased viability and increased apoptosis, which were significantly mitigated by AS-IV. Immunofluorescence showed enhanced Tuj1 expression, indicating increased neuronal purity and survival, enhanced NF200 expression, indicating increased axon lengths. FCM results revealed reduced apoptosis rates, particularly with higher doses of AS-IV. Western blot analysis confirmed inhibition of PTEN and activation of AKT, facilitating enhanced neuronal survival and axona regeneration. Additionally, overexpression of PTEN negated the anti-apoptotic effects of AS-IV, underscoring the critical role of the PTEN/AKT pathway in AS-IV mediated neuroprotection.

Conclusion

AS-IV enhances neuronal survival and axona regeneration by modulating the PTEN/AKT pathway, highlighting its potential as a therapeutic agent for ischemic brain injuries. These findings suggest that targeting this pathway could be a strategic focus for developing effective neuroprotective therapies.

背景：神经元的存活和再生是缺血性脑损伤恢复的关键方面。黄芪甲苷（Astragaloside IV, AS-IV）是一种从中药黄芪中提取的皂苷，具有促进神经细胞健康的作用。本研究探讨AS-IV对氧葡萄糖剥夺（OGD）后神经元存活和凋亡的影响，重点研究其对PTEN/AKT信号通路的调节作用。方法：分离大鼠原代神经细胞，进行OGD模拟缺血状态。然后，用低剂量和高剂量的AS-IV处理细胞。采用MTT和流式细胞术（FCM）检测神经元活力和凋亡。采用免疫荧光和Western blot分析评估PTEN/AKT通路相关神经元标志物和蛋白的表达。结果：ogd后，神经元细胞活力下降，细胞凋亡增加，AS-IV显著缓解。免疫荧光显示Tuj1表达增强，表明神经元纯度和存活率增加；NF200表达增强，表明轴突长度增加。FCM结果显示凋亡率降低，特别是高剂量AS-IV。Western blot分析证实了PTEN的抑制和AKT的激活，促进了神经元存活和轴突再生。此外，PTEN过表达可抑制AS-IV的抗凋亡作用，这表明PTEN/AKT通路在AS-IV介导的神经保护中起着关键作用。结论：as - iv通过调节PTEN/AKT通路增强神经元存活和轴突再生，提示其作为缺血性脑损伤治疗药物的潜力。这些发现表明，靶向这一途径可能是开发有效神经保护疗法的战略重点。

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引用次数: 0

Nitric oxide and peroxynitrite as new biomarkers for early diagnosis of autism 一氧化氮和过氧亚硝酸盐作为自闭症早期诊断的新生物标志物。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-08 DOI: 10.1016/j.brainres.2024.149438

Abdullah Asif Khan, Howard D. Dewald

Autism spectrum disorder, or autism, is a neurodevelopmental disorder of the developing child’s brain with a genetic causality. It can be diagnosed at about three years after birth when it begins to present itself via a range of neuropsychiatric symptoms. Nitric oxide is a crucial small molecule of life synthesized within cells of our body systems, including cells of our brain. Peroxynitrite is the product of reaction between superoxide anion and nitric oxide. It normally isomerizes into harmless nitrates or nitrites. However, when excessive superoxide anion is present, the cellular concentration of peroxynitrite can increase to a toxic level. Autism has been suggested to cause oxidative damage to brain cells. Until now, it is impossible to sample tissue from a live brain. Instead, stem cells can be derived (from an autism patient’s somatic cells) which can then be differentiated and chemically directed to grow into miniature 3-dimensional tissue masses resembling specific brain regions (e.g., the cortex) called brain organoids. This review discusses utilizing nitric oxide and peroxynitrite as biomarkers and comparing their relative concentrations in stem cells and stem cell derived brain organoids of healthy and autistic individuals to develop a bioanalytical process for early diagnosis of autism.

自闭症谱系障碍，或自闭症，是一种发育中的儿童大脑的神经发育障碍，具有遗传因果关系。它可以在出生后大约三岁时被诊断出来，那时它开始通过一系列神经精神症状出现。一氧化氮是一种至关重要的生命小分子，在我们身体系统的细胞中合成，包括我们的大脑细胞。过氧亚硝酸盐是超氧阴离子与一氧化氮反应的产物。它通常会异构化为无害的硝酸盐或亚硝酸盐。然而，当存在过量的超氧阴离子时，过氧亚硝酸盐的细胞浓度可增加到毒性水平。自闭症被认为会导致脑细胞氧化损伤。到目前为止，从活体大脑中提取组织样本是不可能的。相反，干细胞可以（从自闭症患者的体细胞中）获得，然后可以分化并通过化学方法引导生长成类似于特定大脑区域（例如，皮层）的微型三维组织块，称为脑类器官。本文讨论了利用一氧化氮和过氧亚硝酸盐作为生物标志物，并比较它们在健康和自闭症个体的干细胞和干细胞衍生的脑类器官中的相对浓度，以建立自闭症早期诊断的生物分析方法。

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引用次数: 0

Exploring the relationship between MGAT2 and glioblastoma: A Mendelian Randomization and bioinformatics approach 探索MGAT2与胶质母细胞瘤之间的关系：孟德尔随机化和生物信息学方法。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-07 DOI: 10.1016/j.brainres.2025.149449

Zili Qiu , Chengcheng Guo , Xuejiao Liu , Shangfeng Gao , Weihan Xiao , Hai Cheng , Luxin Yin

Background

Mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase 2 (MGAT2) and tumors’ relevant research was in full swing recently. Therefore, we employed Mendelian Randomization (MR) alongside bioinformatics to thoroughly investigate the possible relationship between MGAT2 and glioblastoma (GBM).

Methods

We utilized the summary statistics of genome-wide association studies (GWAS) for MGAT2 (N = 35,559 from deCODE) and glioblastoma (N = 379,155 from FinnGen). MR was used to assess the causal relationship between MGAT2 and GBM. Bioinformatics was used for a more in-depth exploration of the relationship between MGAT2 and GBM.

Results

MR analysis demonstrated a causal relationship, showing that elevated levels of MGAT2 are associated with an increased risk of GBM (OR = 2.59, 95 % CI: 1.13–5.91, p = 0.023). Further investigation revealed significant differences in MGAT2 expression across normal tissue, tumor tissue, and gliomas of different types. Additionally, we found that MGAT2 may influence GBM through immune-related pathways, particularly through the role of macrophages. Proteins associated with MGAT2 were also identified in the PPI network.

Conclusion

This study first validated the causal relationship between MGAT2 and glioblastoma, and used bioinformatics to explore the relationship from multiple perspectives. Additionally, we proposed hypotheses for further research to investigate the potential mechanisms underlying this connection.

背景：甘露糖糖蛋白β -1,2- n -乙酰氨基葡萄糖转移酶2 （MGAT2）及肿瘤相关研究近年来正如日中天。因此，我们采用孟德尔随机化（MR）和生物信息学来彻底研究MGAT2和胶质母细胞瘤（GBM）之间可能的关系。方法：我们利用MGAT2 （N = 35,559来自deCODE）和胶质母细胞瘤（N = 379,155来自FinnGen）的全基因组关联研究（GWAS）的汇总统计。MR用于评估MGAT2与GBM之间的因果关系。利用生物信息学对MGAT2与GBM之间的关系进行了更深入的探讨。结果：MR分析显示了因果关系，显示MGAT2水平升高与GBM风险增加相关（OR = 2.59, 95 % CI: 1.13-5.91, p = 0.023）。进一步研究发现MGAT2在正常组织、肿瘤组织和不同类型胶质瘤中的表达存在显著差异。此外，我们发现MGAT2可能通过免疫相关途径影响GBM，特别是通过巨噬细胞的作用。与MGAT2相关的蛋白也在PPI网络中被鉴定出来。结论：本研究首次验证了MGAT2与胶质母细胞瘤之间的因果关系，并利用生物信息学从多个角度探讨了两者之间的关系。此外，我们提出了进一步研究的假设，以调查这种联系的潜在机制。

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引用次数: 0

Aging and voluntary exercise’s effects on Aβ1-42 levels, endoplasmic reticulum stress factors, and apoptosis in the hippocampus of old male rats 衰老和自主运动对老龄雄性大鼠海马a - β1-42水平、内质网应激因子及细胞凋亡的影响

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-04 DOI: 10.1016/j.brainres.2025.149447

Leila Derafshpour , Mona Niazi , Bagher Pourheydar , Shiva Roshan-Milani , Morteza Asghariehahari , Leila Chodari

Within the aging cortex, amyloid beta peptide (Aβ) is a crucial element of the senile plaques, a hallmark feature often observed in cases of Alzheimer’s disease (AD). The UPR (unfolded protein response), a cellular mechanism for protein folding, is switched on by Aβ accumulation. Endoplasmic reticulum (ER) stress has been identified as playing a role in aging and the development of neurodegenerative diseases. The exact molecular pathways leading to perishing of cells from Aβ-induced ER stress, as well as the impact of voluntary exercise on these mechanisms, are still subjects awaiting a definitive answer yet. In the current study, 18 male Wistar rats were included: 6 young rats (3 months old; 200–250 g) in the Young Control group, and 12 old rats (18 months old; 400–430 g) randomly allocated to the Old Control and Old Exercise groups. The rat cages had running wheels for them to voluntarily run on for 8 weeks. This was followed by Western blotting, immunohistochemical staining, biochemical as well as morphological analyses. Voluntary exercise reduced Aβ1-42 deposition (P < 0.001) and inhibited the activation of caspase-8 (P < 0.001) and caspase-12 (P < 0.01), and on top of that down-regulated the expression of ATF6 (P < 0.001), CHOP (P < 0.01), and p-PERK (P < 0.05) proteins in the hippocampus of old male rats. Exercise amplified the population of Bcl-2-expressing cells and decreased the population of Bax-expressing cells in the hippocampus of the Old Exercise group (P < 0.001). Voluntary exercise inhibited the apoptotic pathways and suppressed the activation of UPR signaling pathways. Hence, voluntary exercise may be a therapeutic strategy and a promising approach to prevent AD through modulation of Aβ-induced ER stress.

在老化的皮层中，淀粉样蛋白β肽（a β）是老年斑的关键成分，老年斑是阿尔茨海默病（AD）病例中经常观察到的标志性特征。未折叠蛋白反应（UPR）是一种蛋白质折叠的细胞机制，是通过a β积累而开启的。内质网应激已被确定在衰老和神经退行性疾病的发展中发挥作用。a β诱导内质网应激导致细胞死亡的确切分子途径，以及自愿运动对这些机制的影响，仍然是等待明确答案的主题。本研究共纳入18只雄性Wistar大鼠：6只幼龄大鼠(3月龄；青年对照组200 ~ 250 g)，老年大鼠12只(18月龄；400-430 g)，随机分配到老年对照组和老年运动组。老鼠笼子里有跑轮供它们自愿跑8周。随后进行免疫印迹、免疫组织化学染色、生化和形态学分析。自愿运动减少a - β1-42沉积(P

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引用次数: 0

The effect of Naringin on cognitive function, oxidative stress, cholinergic activity, CREB/BDNF signaling and hippocampal cell damage in offspring rats with utero-placental insufficiency-induced intrauterine growth restriction 柚皮苷对子宫胎盘功能不全所致宫内生长受限子代大鼠认知功能、氧化应激、胆碱能活性、CREB/BDNF信号传导及海马细胞损伤的影响

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-04 DOI: 10.1016/j.brainres.2025.149448

Samireh Nemati , Mohammad Amin Edalatmanesh , Mohsen Forouzanfar

Intrauterine growth restriction (IUGR) induced by utero-placental insufficiency (UPI) results in delayed neural development and impaired brain growth. This study investigates the effects of Naringin (Nar) on memory, learning, cholinergic activity, oxidative stress markers, hippocampal CREB/BDNF signal pathway and cell damage in offspring of rats exposed to UPI. Twenty pregnant Wistar rats were randomly assigned to four groups: control, sham surgery, UPI + NS (UPI + normal saline as a vehicle), and UPI + Nar (UPI + Nar at 100 mg/kg/day). UPI was induced by permanently occluding the uterine anterior vessels on embryonic day (ED) 18. Naringin or saline was administered orally from ED15 to ED21. Behavioral assessments of offspring, including working memory, avoidance learning, and anxiety-like behavior, were conducted on a postnatal day (PND) 21. Subsequently, hippocampal acetylcholinesterase (AChE) activity, catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA), hippocampal transcript level of cyclic AMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) and apoptotic neuron density in the hippocampus were evaluated. Naringin-treated rats demonstrated significant improvements in working and avoidance memory, increases in CAT, SOD, and TAC, CREB, BDNF and reductions in AChE activity, MDA levels, apoptotic neuron density, and anxiety-like behaviors compared to the UPI + NS group (p < 0.05). Naringin mitigates hippocampal cell damage, cognitive impairments, and anxiety by enhancing antioxidant defenses, modulating cholinergic activity and CREB/BDNF signaling in the brains of UPI-exposed offspring.

子宫胎盘功能不全（UPI）引起的宫内生长限制（IUGR）导致神经发育迟缓和大脑发育受损。本研究探讨柚皮苷（Naringin, Nar）对UPI暴露大鼠后代的记忆、学习、胆碱能活性、氧化应激标志物、海马CREB/BDNF信号通路和细胞损伤的影响。将20只妊娠Wistar大鼠随机分为4组：对照组、假手术组、UPI + NS组（UPI +生理盐水为载体）、UPI + Nar组（UPI + Nar剂量为100 mg/kg/day）。在胚胎日（ED） 18时，通过永久阻塞子宫前血管诱导UPI。在ED15至ED21期间口服柚皮苷或生理盐水。后代的行为评估，包括工作记忆、回避学习和焦虑样行为，在出生后一天（PND） 21进行。随后，评估海马乙酰胆碱酯酶（AChE）活性、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、总抗氧化能力（TAC）、丙二醛（MDA）、海马环AMP反应元件结合蛋白（CREB）和脑源性神经营养因子（BDNF）转录物水平以及海马细胞凋亡神经元密度。与UPI + NS组相比，柚皮素处理的大鼠在工作和回避记忆方面表现出显著改善，CAT、SOD、TAC、CREB、BDNF水平增加，AChE活性、MDA水平、凋亡神经元密度和焦虑样行为降低(p

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引用次数: 0

A non-purine inhibitor of xanthine oxidoreductase mitigates adenosine triphosphate degradation under hypoxic conditions in mouse brain 黄嘌呤氧化还原酶的非嘌呤抑制剂减轻小鼠大脑缺氧条件下三磷酸腺苷的降解。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-02 DOI: 10.1016/j.brainres.2025.149444

Nana Sato , Teruo Kusano , Koji Nagata , Ken Okamoto

The brain is an organ that consumes a substantial amount of oxygen, and a reduction in oxygen concentration can rapidly lead to significant and irreversible brain injury. The progression of brain injury during hypoxia involves the depletion of intracellular adenosine triphosphate (ATP) due to decreased oxidative phosphorylation in the inner mitochondrial membrane. Allopurinol is a purine analog inhibitor of xanthine oxidoreductase that protects against hypoxic/ischemic brain injury; however, its underlying mechanism of action remains unclear. In addition, febuxostat is a non-purine xanthine oxidoreductase inhibitor with a different inhibitory mechanism from allopurinol. The impact of febuxostat on brain injury has not been well investigated. Therefore, this study aimed to examine brain ATP and its catabolite levels in the presence or absence of allopurinol and febuxostat under hypoxic conditions by inactivating brain metabolism using focal microwave irradiation. The hypoxic treatment caused a decrease in the adenylate energy charge and ATP levels and an increase in its catabolic products in mouse brains. The febuxostat group showed higher energy charge and ATP levels and lower ATP catabolites than the control group. Notably, despite the comparable suppression of uric acid production in both inhibitor groups, allopurinol treatment was less effective than febuxostat. These results suggest that febuxostat effectively prevents hypoxia-induced ATP degradation in the brain and that its effect is more potent than allopurinol. This study will contribute to developing therapies for improving hypoxia-induced brain dysfunction.

大脑是一个消耗大量氧气的器官，氧气浓度的降低会迅速导致严重的、不可逆转的脑损伤。缺氧时脑损伤的进展涉及细胞内三磷酸腺苷（ATP）的消耗，这是由于线粒体内膜氧化磷酸化的减少。别嘌呤醇是黄嘌呤氧化还原酶的嘌呤类似物抑制剂，可防止缺氧/缺血性脑损伤；然而，其潜在的作用机制尚不清楚。此外，非布司他是一种非嘌呤黄嘌呤氧化还原酶抑制剂，其抑制机制与别嘌呤醇不同。非布司他对脑损伤的影响尚未得到很好的研究。因此，本研究旨在通过局灶微波灭活脑代谢，检测缺氧条件下别嘌呤醇和非布司他存在或不存在时脑ATP及其分解代谢物的水平。低氧处理导致小鼠大脑中腺苷酸能量电荷和ATP水平下降，其分解代谢产物增加。与对照组相比，非布司他组的能量电荷和ATP水平较高，ATP分解产物较低。值得注意的是，尽管两种抑制剂组对尿酸产生的抑制效果相当，但别嘌呤醇治疗的效果不如非布司他。这些结果表明，非布司他能有效地防止缺氧诱导的脑内ATP降解，其作用比别嘌呤醇更有效。本研究将有助于开发改善缺氧引起的脑功能障碍的治疗方法。

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引用次数: 0

Identifying the appropriate measurement environment for laser speckle flowmetry of cerebral blood flow in rats 确定激光散斑血流法测量大鼠脑血流的适宜环境。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-02 DOI: 10.1016/j.brainres.2025.149443

Ryosei Wakasa, Takahiro Ono, Naomoto Senbokuya, Mikiko Kuwayama, Hiroaki Shimizu

Laser speckle flowmetry (LSF) is a noninvasive tool for cerebral blood flow (CBF) measurement via a cranial bone window. LSF is influenced by various factors including the extent of removal of bone and dura mater and tissue wetness in the bone window. In this study, we aimed to characterize the effect of these conditions on LSF signals and identify optimal measurement conditions for CBF LSF measurements in rats. Three bone windows were created over the Sprague-Dawley rat brains including (i) bone removal until the brain surface was visible through the thin skull, (ii) complete bone removal for dura mater exposure, and (iii) dura mater removal for cortical surface exposure. We investigated the difference in the LSF signals of these windows under dry and wet conditions. The differences between signals obtained using artificial cerebrospinal fluid (aCSF) and mineral oil for wet conditions were also examined. Furthermore, we investigated the stability of repeated CBF measurements in thinned skulls over 15 days and the effects of gentamicin ointment. No significant difference was observed in the LSF values of the three bone windows under dry and wet conditions. Moreover, mineral oil may provide better LSF signal stability. CBF LSF measurements with minimum signal fluctuation were possible for 15 days using the thinned skull window with gentamicin ointment. In conclusion, CBF LSF measurements are feasible in rats using thinned skulls or dura matter in dry or wet environments, preferably with mineral oils. Relatively repetitive CBF LSF measurements were possible for long duration using gentamicin ointment for daily wound closure.

激光散斑血流仪（LSF）是一种通过颅骨窗测量脑血流量（CBF）的无创工具。LSF受多种因素的影响，包括骨和硬脑膜的去除程度以及骨窗组织的湿润程度。在本研究中，我们旨在表征这些条件对LSF信号的影响，并确定大鼠CBF LSF测量的最佳测量条件。在Sprague-Dawley大鼠脑上创建了三个骨窗，包括(i)骨移除直到薄颅骨可见脑表面，（ii）完全骨移除以暴露硬脑膜，（iii）硬脑膜移除以暴露皮质表面。我们研究了这些窗口在干燥和潮湿条件下LSF信号的差异。还研究了在潮湿条件下使用人工脑脊液（aCSF）和矿物油获得的信号之间的差异。此外，我们研究了在变薄的颅骨中重复测量CBF超过15 天的稳定性和庆大霉素软膏的效果。干、湿条件下三种骨窗的LSF值无显著差异。此外，矿物油可能提供更好的LSF信号稳定性。使用庆大霉素软膏的薄颅骨窗，可以在15 天内测量最小信号波动的CBF LSF。综上所述，CBF LSF测量是可行的，在潮湿环境中使用变薄的大鼠颅骨，最好使用矿物油。使用庆大霉素软膏进行每日伤口闭合，可以在较长时间内相对重复的CBF LSF测量。

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