Aging Leads to Over-Expression of Na⁺/K⁺Pump Units in Liver and Na⁺/Ca²⁺Exchangers in Brain Cortex

The metabolic controlling of tissue hydration is the fundamental parameter determining cell functional activity and its dysfunction is the common consequence of any cell pathology, including aging. The aim of the present study is to reveal the differences of age-dependent metabolic controlling of cell hydration of excitable tissue such as brain cortex and non-excitable tissues such as liver and spleen. For this purpose, the age-dependent sensitivity of cell hydration in excitable and non-excitablet issues is studied through depressing metabolic activity by cooling and its activation by supplying animals with distilled water, by inactivation of Na+/K+ pump and activation of Na+/Ca2+ exchange in the reverse mode. The obtained data bring us to the conclusion that the metabolic regulation of cell hydration in excitable tissue is realized by the activation of electrogenic Na+/K+ pump and Na+/Ca2+ exchange in the cell membrane and the formation of endogen water by mitochondrial activity, while the regulation of cell hydration in non-excitable tissue is carried out only by the activity of mitochondrial function. Aging leads to an over-expression of Na+/K+ pump units in liver and Na+/Ca2+ exchanger in brain cortex of rats.

Neuropsychological Profile of a Patient with Acquired Brain Damage Following Vascular Lesion of the Left Anterior Cingulate Cortex

Stroke is a physiological alteration associated with changes in blood flow that can result in sudden-onset cognitive impairment. It has a heterogenous clinical presentation with varying degrees of severity correlated with specific central nervous system zones or areas, and its prognosis is uncertain. This case study describes a 62-year-old male patient with acquired brain damage of the anterior cingulate cortex as a result of an ischemic event in the territory of the left anterior cerebral artery. Cognitive function was assessed using the neuropsychological executive function and frontal lobe test battery (BANFE-2) as well as other neuropsychological tests. The results show a profile of higher mental functions characterized by the presence of dysexecutive syndrome with marked behavioral alteration and diencephalic amnesia. .

Distinct proteins in cortex of rats with closed traumatic brain injury detected by a WCX-2 protein chip

BACKGROUND： Mechanical injury can cause the changes of polygene expression spectrum in rat cerebral cortical nerve cells, and then result in the changes of intracellular protein expression. At present, dielectrophoresis is combined with mass spectrum technique to detect the expression of different proteins in rat cortex after brain injury, but the protein chip technique requires further investigation. OBJECTIVE： To analyze the differences of protein expression spectrum in rat cerebral cortex before and after closed traumatic brain injury using WCX-2 protein chip technique. DESIGN： A randomized controlled animal experiment. SETTING： Training Division of the Medical College of Chinese People＇s Armed Police Force. MATERIALS： Seventy-two male SD rats of clean degree, 350 - 450 g, were provided by the Experimental Animal Center, Academy of Military Medical Sciences of Chinese PLA. Urea, trifluoroacetic acid, CHAPS and Tris （Sigma, USA）; WCX-2 （Ciphergen, USA）. Ultra-high speed hypothermia centrifuger （Bechman, USA）; Rotary tissue microtome （Keuca, Germany）; Biochip processor and PBS II-C protein chip reader （Ciphergen, USA）. METHODS： The experiments were carried out in the Institute of Molecular Pathology, Central Laboratory, and Department of Pathology, Medical College of Chinese People＇s Armed Police Force from June 2005 to March 2006. ① Grouping and treatment： The experiments were completed in molecular pathological institute, central laboratory and pathological department. ② The rats were randomly divided into control group （n =12） and brain injury group （n =60）. Marmarou＇s weight-dropping models were duplicated at different time points in the brain injury group. In the control group, the rats were only treated by incising the skin of head top, without fixing the stainless steel hitting backup plate at the vault of skull, and obtain brain cortex for pathological and protein chip research, and they were killed after 24 hours. The rats in the brain injury group were killed at 4, 8, 12, 24 and 48 hours after model establishment. ③ Pathological observation： Longitudinal section was made on cerebral cortex, and sections of 5 μm were prepared, then stained with hematoxylin and eosin （HE）. ④Protein chip analysis： 100 mg cerebral cortex was collected from each rat, and the protein content in sample was detected with Bradford method, meanwhile, WCX-2 protein chip was used to analyze the protein spectrum. The data were automatically collected with Ciphergen proteinchip 3.0 software, and the results were analyzed using Biomarker Wizard software to compare the differences of protein spectrum in rat cortex between the groups. MAIN OUTCOME MEASURES： Results of the pathological observation of cerebral cortex and the protein spectrum analysis. RESULTS：①Pathological changes of cerebral cortex： In the control group, no necrosis and edema was observed. In the brain injury group, injures of different severity occurred at different time points; After 4 hours, focal or scattered red nerve cells could be observed, the size of some cells was increased, cytoplasm was lightly stained, and only nuclear fragments were seen; After 8 hours, the necrotic nerve cells were increased, and the number of nerve cells was reduced, astrocytes （neuronophagia） could be seen in partial cytoplasm; there was small vascular dilatation, and endothelial cell proliferation; interstitial edema, regional rarefaction lightly stained. After 12- 48 hours, the necrotic nerve cells were reduced, and astrocytes proliferated. ② Results of protein spectrum analysis： The WCX-2 experiment found that the expressions of 5 639, 3 212 and 7 536 u proteins in cerebral cortex changed after injury in the brain injury group. The peak intensity of 5 639 u protein in the brain injury group at 8 hours after injury was higher than that in the control group （P 〈 0.05）; The peak intensity of 3 212 u protein in the brain injury group at 48 hours after injury was higher than that in the control group （P 〈 0.05）; The peak intensity of 7 536 u protein at 24 hours after injury was higher than that in the control group （P 〈 0.05）. CONCLUSION： Brain injury can cause the changes of protein expression spectrum in cerebral cortex, it is suggested that brain injury can induce the expression of protein.

FUNCTIONAL MAPPING OF THE HUMAN BRAIN DURING ACUPUNCTURE WITH MAGNETIC RESONANCE IMAGINGSOMATOSENSORY CORTEX ACTIVATION

Hegu (LI 4) is one of the most frequently used and most important analgesic points in Chinese acupuncture. It is particularly effective for treating disorders of the head and face. According to the meridian theory in Traditional Chinese Medicine (TCM), the Large Intestine Meridian to which it belongs originates in the hand and terminates in the face. This theory is based, however, more on thousands of years of clinical experience rather than on scientific evidence. In our study of acupuncture effects on normal human volunteers with the non-invasive BOLD (blood oxygenation level dependant)technique for FMRI (functional magnetic resonance imaging), we demonstrated widespread effects in the brain during acupuncture at Hegu and Zusanli (ST 36). A finding of special interest was observed in the primary somatosensory cortes (SI) during Hegu acupuncture. In additlon to activation of the area representing the hand in response to the sensory impulses arising from the site of stimulation, activation also occurred in the face representation in all 3 subjects brains studied by coronal brain sections. In one of these subjects activation in the face representation was even stronger than that in the hand representation. Areas representing the neck, trunk and other parts of the upper extremity also exhibited increase in signal intensity, subject to individual variability. As compared with Hegu, such effects were either absent or much weaker with acupuncture at Zusanli (ST 36) or with other forms of sensory stimulation to the hand. Functional mapping of the brain with MRI has provided the first direct evidence in support of the important role of Hegu acupuncture in TCM.

Wake-promoting effects of vagus nerve stimulation after traumatic brain injury: upregulation of orexin-A and orexin receptor type 1 expression in the prefrontal cortex

Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expres- sion coincides with the projection area of the vagus nerve in the brain. Vagus nerve stimulation has been shown to decrease the amounts of daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury. In the present study, we investigated whether vagus nerve stimulation promotes wakefulness and affects orexin expression. A rat model of traumatic brain injury was established using the free fall drop method. In the stimulated group, rats with traumatic brain injury received vagus nerve stimulation （frequency, 30 Hz, current, 1.0 mA; pulse width, 0.5 ms; total stimulation time, 15 minutes）. In the antagonist group, rats with traumatic brain injury were intracerebroventricularly injected with the orexin receptor type 1 （OXIR） antagonist SB334867 and received vagus nerve stimulation. Changes in consciousness were observed after stimulation in each group. Enzyme-linked immunosorbent assay, western blot assay and immunohistochemistry were used to assess the levels of orexin-A and OX1R expression in the prefrontal cortex. In the stimulated group, consciousness was substantially improved, orexin-A protein expression gradually increased within 24 hours after injury and OX1R expres- sion reached a peak at 12 hours, compared with rats subjected to traumatic brain injury only. In the antagonist group, the wake-promoting effect of vagus nerve stimulation was diminished, and orexin-A and OX1R expression were decreased, compared with that of the stim- ulated group. Taken together, our findings suggest that vagus nerve stimulation promotes the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OXIR expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.

Electroacupuncture stimulation of the brachial plexus trunk on the healthy side promotes brain-derived neurotrophic factor mRNA expression in the ischemic cerebral cortex of a rat model of cerebral ischemia/reperfusion injury

A rat model of cerebral ischemia/reperfusion was established by suture occlusion of the left middle cerebral artery. In situ hybridization results showed that the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic rat cerebral cortex increased after cerebral ischemia/ reperfusion injury. Low frequency continuous wave electroacupuncture （frequency 2-6 Hz, current intensity 2 mA） stimulation of the brachial plexus trunk on the healthy （right） side increased the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic cerebral cortex 14 days after cerebral ischemia/reperfusion injury. At the same time, electroacupuncture stimulation of the healthy brachial plexus truck significantly decreased neurological function scores and alleviated neurological function deficits. These findings suggest that electroacupuncture stimulation of the brachial plexus trunk on the healthy （right） side can greatly increase brain-derived neurotrophic factor mRNA expression and improve neurological function.

Role of the Dorsal Anterior Cingulate Cortex in Relational Memory Formation: A Deep Brain Activity Index Study

The dorsal area of the anterior cingulate cortex (ACC) constructs the salience network associated with the anterior insular cortex. Conventional brain imaging studies, such as functional magnetic resonance imaging (fMRI), have demonstrated that relational memory formation occurs in the ACC. However, how such memory is encoded and retrieved remains unknown due to limited time resolution of conventional fMRI. This study aimed to investigate temporal dynamics of the dorsal ACC (dACC) during word-pair tasks based on a newly developed event-related deep brain activity (ER-DBA) method using occipital electroencephalogram (EEG) signal powers. The method assesses dACC activity at a temporal resolution of approximately 0.3 s beyond the conventional resolution limit. We found that transient deactivation of dACC during the presentation of the second word of each pair was essential for encoding success regardless of whether the words were related or unrelated. We also found that memory accuracy was not affected by the intervention of inter-trials until the recall trial. Taken together, these findings suggest that dACC deactivation for encoding success is accompanied with short-term potentiation essential for durability of memory. We further found that false memory formation associated with the presentation of word pairs was occasionally committed. In such cases, dACC exhibited a similar transient deactivation although false memory commission was independent of related or unrelated conditions. Our findings suggest that encoding and retrieval of associates are paralleled and that simultaneous production of associates seems to be an essential strategy for successful relational memory formation. The study was limited to the assessment of dACC activity and did not account for other regional brain activities or receptor regulation related to short-term potentiation. We detected fast behavior of dACC during relational memory formation using the novel ER-DBA method. Such temporal dynamics will be important for eliciting underlying mechanisms of memory dysfunctions.

Auditory deprivation modifies the expression of brain-derived neurotrophic factor and tropomyosin receptor kinase B in the rat auditory cortex

The development and plasticity of central auditory system can be influenced by the change of peripheral neuronal activity. However, the molecular mechanism participating in the process remains elusive. Brain-derived neurotrophic factor(BDNF) binding with its functional receptor tropomyosin receptor kinase B(TrkB) has multiple effects on neurons. Here we used a rat model of auditory deprivation by bilateral cochlear ablation, to investigate the changes in expression of BDNF and Trk B in the auditory cortex after auditory deprivation that occurred during the critical period for the development of central auditory system. Reverse transcription-quantitative polymerase chain reaction(RTqPCR) and immunohistochemistry methods were adopted to detect the m RNA and protein expression levels of BDNF and TrkB in the auditory cortex at 2, 4, 6 and 8 weeks after surgery, respectively. The change in the expression of BDNF and TrkB mRNAs and proteins followed similar trend. In the bilateral cochlear ablation groups, the BDNF-TrkB expression level initially decreased at 2 weeks but increased at 4 weeks followed by the reduction at 6 and 8 weeks after cochlear removal, as compared to the age-matched sham control groups. In conclusion, the BDNF-TrkB signaling is involved in the plasticity of auditory cortex in an activity-dependent manner.

脑白质病变及大脑皮层厚度与老年轻型卒中后认知功能障碍的相关性研究

目的探讨老年轻型卒中后认知功能障碍(PSCI)与脑白质病变、大脑皮层厚度的关系。方法回顾性分析158例老年轻型卒中病人的临床资料,根据MoCA评估结果分为非PSCI组和PSCI组(MoCA<26分),比较2组的基线资料、MRI影像改变、大脑皮层厚度,并采用多因素Logistic回归分析老年轻型卒中病人发生PSCI的影响因素。结果PSCI组与非PSCI组的腔隙性缺血灶、脑微出血、DWI阳性病变及血管间隙扩大检出率差异无统计学意义(P>0.05)。PSCI组年龄大于非PSCI组,脑白质病变较非PSCI组严重(P<0.05)。2组的左额下回三角部及右额下回三角部皮质厚度差异无统计学意义(P>0.05),但PSCI组左眶额部、右眶额部、左额中回及右额中回的皮质厚度均明显低于非PSCI组(P<0.05)。多因素分析显示,年龄、中重度脑白质病变均为老年轻型卒中病人发生PSCI的危险因素(OR=1.704、1.826,均P<0.05),前额叶脑皮质厚度(左眶额部、右眶额部、左额中回、右额中回)为老年轻型卒中病人发生PSCI的保护因素(OR=0.820、0.838、0.834、0.827,均P<0.05)。结论年龄、脑白质中重度病变及前额叶脑皮质厚度变薄均与PSCI密切相关,通过头颅MRI检查脑白质及大脑皮质厚度变化,可为临床预测PSCI的发生提供参考依据。

感觉编码时空活动模式的类脑表达与计算——架构篇

大脑如何处理随时间和空间变化的感觉数据流,以执行复杂的认知计算和适应性行为控制,一直是脑科学和类脑技术领域的重要难题。这被称为感觉编码的表达与计算问题,其关键在于找到一种通用的方法,使大脑能够有效地学习和表达感觉数据流中的相似性或不变性,并将这些学习结果应用于认知计算、行为控制以及感知觉和意识形成。然而,现有的实验手段、理论框架和方法体系在揭示大脑生物学结构与功能的复杂关系,以及信息论上类脑智能表达与计算的通用机制方面仍面临挑战,更难以深入阐述这两者之间的内在联系。本文基于视网膜-外侧膝状体-视皮质轴神经编码的生理机制,提出构建一种新型的类脑智能单元模型架构,该架构专注于表达与计算感觉数据流的时空活动模式的相似性或不变性。它不仅模拟了人类大脑外周神经系统对信息的压缩表达、丘脑系统的有序分离与拼接、皮质的独立稀疏编码以及自组织映射计算等复杂过程,还模拟了皮质脑区间折返连接振荡与相干振荡的全局编码机制。这种类脑智能单元不仅为构建大规模集成神经网络模型提供了坚实的基础,而且有助于更深入地理解大脑的表达与计算机制,为实现意识的大脑皮质连接图的全局编码提供新的视角,进而推动类脑智能的实现。

经颅直流电刺激不同靶点治疗帕金森病效果的网状Meta分析

目的:系统评价经颅直流电刺激对帕金森患者运动功能的康复疗效,并比较经颅直流电刺激作用于不同靶点对帕金森患者运动功能的疗效差异,为临床中经颅直流电刺激的靶点选择提供理论依据。方法:计算机检索Cochrane Library、PubMed、Web of Science、中国知网、维普和万方数据库,以“帕金森、经颅直流电刺激”为中文检索词,以“Parkinson,transcranial direct current stimulation”为英文检索词,收集从各数据库建库至2023年1月发表的关于经颅直流电刺激改善帕金森患者运动功能的随机对照试验。使用Cochrane 5.1.0偏倚风险评估工具和PEDro量表对纳入研究进行质量评价。采用RevMan 5.4和Stata 17.0软件对结局指标进行Meta分析。结果:①最终纳入15项随机对照试验,PEDro量表评估显示均为高质量或极高质量研究。②Meta分析显示,与对照组相比经颅直流电刺激可显著提高UPDRS-Ⅲ评分(MD=-2.49,95%CI:-4.42至-0.55,P<0.05)、步频评分(MD=0.07,95%CI:0.03-0.11,P<0.05)和步速评分(MD=0.02,95%CI:0.00-0.05,P<0.05),但对BBS评分(MD=2.57,95%CI:-0.74-5.87,P>0.05)的提高不明显。③网状Meta分析概率排序结果显示,在UPDRS-Ⅲ评分方面,刺激靶点疗效的概率排序结果为背外侧前额叶皮质(52.4%)>初级皮质运动区(45.8%)>大脑中央点(1.8%)>常规康复治疗(0%);在步频评分方面,刺激靶点疗效的概率排序结果为小脑(50.1%)>大脑中央点(45.8%)>背外侧前额叶皮质(3.9%)>初级皮质运动区(0.2%)>常规康复治疗(0%);在步速评分方面,刺激靶点疗效的概率排序结果为小脑(64.8%)>背外侧前额叶皮质(23.8%)>大脑中央点(9.4%)>初级皮质运动区(1.7%)>常规康复治疗(0.4%);在BBS评分方面,刺激靶点疗效的概率排序结果为:小脑(77.4%)>背外侧前额叶皮质(20.7%)>大脑中央点(0.7%)>常规康复治疗(0.2%)。结论:经颅直流电刺激可显著改善帕金森患者运动功能,其中刺激背外侧前额叶皮质区域对改善帕金森患者运动协调方面疗效更佳,而刺激小脑区域对改善帕金森患者步行和平衡方面疗效更佳。

Three-dimensional imaging of spatio-temporal dynamics of small blood capillary network in the cortex based on optical coherence tomography:A review

Optical coherence tomography angiography(OCTA)has emerged as an advanced in vivo im-aging modality,which is widely used for the clinic ophthalmology and neuroscience research in the rodent brain cortex among others.Based on the high numerical aperture(NA)probing lens and the motion-corrected algorithms,a high-resolution imaging technique called OCT micro-angiography is applied to resolve the small blood capillary vessels ranging from 5μm to 10μm in diameter.As OCT-based techniques are recently evolving further from the structural imaging of capillaries toward spatio-temporal dynamic imaging of blood flow in capillaries,here we present a review on the latest techniques for the dynamic flow imaging.Studies on capillary blood flow using these techniques will help us better understand the roles of capillary blood flow for normal functioning of the brain as well as how it malfunctions in diseases.

基于Freesurfer自动分割技术评估不同类型颞叶癫痫患者大脑皮层厚度的改变

目的探讨Freesurfer自动分割技术评估成人颞叶癫痫(TLE)大脑皮层厚度的变化。资料与方法回顾性收集2021年1月—2023年9月宁夏医科大学总医院经临床表现和脑电图共同确诊的84例TLE,包括MRI阴性TLE 32例、左侧海马硬化30例、右侧海马硬化22例,招募50例健康志愿者作为对照组,均行轴位T1WI三维磁化强度预备梯度回波序列扫描。使用Freesurfer软件对T1WI图像行大脑皮层分割,比较不同类型TLE患者各皮层厚度的差异。结果MRI阴性TLE组与对照组比较有14个区域皮层厚度均减小,主要集中在双侧额叶和右侧顶叶,差异有统计学意义(P均<0.05);左侧海马硬化组与对照组比较有34个区域皮层厚度均减小,主要集中在双侧额叶、颞叶及顶叶,差异有统计学意义(P均<0.05);右侧海马硬化组与对照组比较有27个区域皮层厚度均减小,主要集中在双侧额叶、顶叶及右侧颞叶,差异有统计学意义(P均<0.05)。结论自动分割技术可评价不同类型TLE患者大脑不同皮层区域厚度的变化,有助于临床进一步了解TLE的发展,为完善治疗方法或术前评估提供参考。

Cortex ID分析法用于^(18)F-FDG PET脑显像术前定位局灶性脑皮质发育不良致痫灶的临床价值分析

背景局灶性脑皮质发育不良(FCD)的治疗主要依靠外科切除致痫灶,其疗效及远期预后与致痫灶的准确定位密切相关。正电子发射断层扫描(PET)脑显像在致痫灶定位诊断中具有优势。既往采用PET脑显像依靠视觉分析法进行诊断,受医师主观因素影响大。目的探讨Cortex ID分析法用于^(18)F-脱氧葡萄糖(FDG)PET脑显像术前定位FCD致痫灶的临床应用价值。方法回顾性分析2013年2月——2017年6月就诊于河北省人民医院并行手术治疗的局灶性癫痫患者34例,经术后病理检查证实为FCD所致癫痫。术前均行发作间期^(18)F-FDG PET脑显像,分别采用视觉分析法和Cortex ID分析法进行术前致痫灶定位,以术后病理检查结果为金标准,比较两种方法对FCD致痫灶的诊断价值。结果 34例FCD患者依据金标准证实有41个FCD致痫灶,视觉分析法对FCD致痫灶的检出率为70.7%(29/41),Cortex ID分析法对FCD致痫灶的检出率为82.9%(34/41);两种方法对FCD致痫灶的检出率比较,差异无统计学意义(χ~2=0.191,P=0.295)。两种方法对FCD致痫灶的诊断具有一致性(Kappa=0.396,P=0.007)。结论 Cortex ID分析法与视觉分析法对FCD致痫灶检出率无显著差异,两种方法诊断FCD致痫灶一致性一般。Cortex ID分析法重复性好,受主观影响小。

褪黑素通过PI3K/AKT通路减轻缺氧缺血性脑损伤新生大鼠大脑皮层神经细胞自噬的研究

目的 观察褪黑素(melatonin,Mel)对缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)新生大鼠大脑皮层神经细胞自噬的影响,并从PI3K/AKT信号通路探讨其机制,为Mel的临床应用提供依据。方法 将7日龄Sprague-Dawley新生大鼠随机分为假手术组、HIBD组及Mel组(各组n=9)。采用经典RiceVannucci法构建新生大鼠HIBD模型。采用苏木精-伊红和尼氏染色法观察新生大鼠大脑皮层神经细胞形态;免疫荧光染色和Western blot法检测自噬相关蛋白微管相关蛋白1轻链3 (microtubule-associated protein 1 light chain3,LC3)及Beclin-1蛋白表达水平;免疫组化和Western blot法检测磷酸化磷脂酰肌醇3-激酶(phosphorylated phosphoinositide 3-kinase,p-PI3K)、磷酸化蛋白激酶B (phosphorylated protein kinase B,p-AKT)蛋白表达水平;通过Pearson相关性分析探讨Mel组与HIBD组自噬与PI3K通路的相关性。结果 建模后24h,假手术组新生大鼠大脑皮层神经细胞大小形态正常、排列规则,HIBD组神经细胞胞体肿胀、排列不规则,Mel组神经细胞排列较规整、形态相对正常。假手术组尼氏小体形态规整,HIBD组尼氏小体形态异常,Mel组尼氏小体形态尚规整。HIBD组LC3及Beclin-1平均荧光强度较假手术组增加,Mel组较HIBD组减少(P<0.05)。HIBD组p-PI3K^(+)、pAKT^(+)细胞数较假手术组减少,Mel组较HIBD组增加(P<0.05)。HIBD组LC3、Beclin-1蛋白表达水平较假手术组增加,p-PI3K、p-AKT蛋白表达水平较假手术组减少(P<0.05);Mel组LC3、Beclin-1蛋白表达水平较HIBD组减少,p-PI3K、p-AKT蛋白表达水平较HIBD组增加(P<0.05)。相关性分析显示,Mel组与HIBD组损伤侧大脑皮层LC3、Beclin-1蛋白平均荧光强度差值与p-PI3K^(+)、p-AKT^(+)细胞数差值均呈负相关(P<0.05)。结论 Mel可抑制HIBD新生大鼠大脑皮层神经细胞过度自噬,从而减轻HIBD,其机制与PI3K/AKT通路相关。

脊髓损伤重塑皮质脊髓运动神经元突触输入的作用

背景:脊髓损伤后的功能恢复依赖于运动皮质的功能重塑,然而运动皮质功能重塑的解剖基础研究较少,了解脊髓损伤后运动皮质功能的解剖变化可对脊髓损伤后功能恢复的调控以及康复治疗等提供新的思路以及研究方向。目的:解析脊髓损伤后初级运动皮质功能重塑的神经回路结构基础。方法:C57BL/6J小鼠随机分为假手术组、脊髓损伤组。向两组小鼠C4脊髓注射表达Cre重组酶融合蛋白的腺相关病毒,同时在大脑初级运动皮质注射Cre重组酶依赖的分别表达禽类肉瘤/白血病病毒包膜蛋白受体TVA和狂犬病毒糖蛋白的假性狂犬病毒辅助腺相关病毒。第14天时脊髓损伤组小鼠建立C6脊髓背侧半切模型,同时向两组小鼠初级运动皮质注射假性狂犬病毒,7 d后收集小鼠脑部样本,制作冰冻切片,观察支配皮质脊髓运动神经元的输入神经元在脑内的分布情况并进行定量分析。结果与结论:荧光显微镜观察及定量分析结果发现,两组小鼠支配初级运动皮质脊髓运动神经元的输入神经元在大脑皮质、间脑和中脑均有分布。其中,假手术组小鼠大脑皮质的输入神经元占全脑输入神经元总数的(84.0±3.6)%,间脑占(10.6±2.3)%,中脑占(0.7±0.4)%;脊髓损伤组直接突触的输入神经元在皮质、间脑和中脑中的占比分别为(81.7±1.0)%,(13.1±0.5)%和(1.6±0.8)%。脊髓损伤组初级运动皮质输入神经元在3个区域的比例以及数量均与假手术组无明显差异。脊髓损伤后,各脑区内支配皮质脊髓运动神经元的输入神经元数量无明显变化,提示皮质脊髓束受损后初级运动皮质的功能重塑可能不仅依赖于受损皮质脊髓运动神经元相关突触输入的改变,而更多地与受损神经元自身的转录调控变化有关。

有氧运动通过“脑-心”轴抑制交感神经过度激活改善心肌梗死小鼠心功能

目的:探讨有氧运动改善心肌梗死小鼠心功能的中枢机制。方法:C57BL/6J小鼠随机分为假手术组(Sham)、心肌梗死组(MI)、心肌梗死运动组(ME),每组12只;光遗传激活组(ChR2)、光遗传抑制组(eNpHR3.0),每组6只;心肌梗死对照组(MI+Dio)、心肌梗死+初级运动皮层(primary motor cortex,M1)区神经元消融组(MI+taCasp3),每组6只。采用左冠状动脉前降支结扎术制备心肌梗死模型,术后1周对ME组进行6周有氧运动干预。心脏注射伪狂犬病病毒(pseudorabies virus,PRV)逆行跨多突触标记,以解析中枢与心脏的神经通路。通过光遗传激活或抑制初级运动皮层M1区谷氨酸(Glutamate,Glu)能神经元,以及神经元消融技术沉默初级运动皮层M1区Glu能神经元,探究初级运动皮层M1区Glu能神经元对心脏交感神经活动的影响。采用Masson和苏木精-伊红染色评估心脏结构病理变化,心电图检测心率变异性,心动超声评定心功能,试剂盒检测血清去甲肾上腺素(norepinephrine,NE)含量。利用Western blot和免疫荧光检测心脏的交感神经标记物酪氨酸羟化酶(tyrosine hydroxylase,TH)、神经生长因子(neu‐rotrophic factor,NGF)、生长相关蛋白43(growth-associated protein 43,GAP43)的表达,以及M1区神经元裂解型半胱氨酸蛋白酶-3(c-Caspase3)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin 6,IL-6)蛋白表达。采用尼氏染色和微管关联蛋白2(microtubule associated protein 2,MAP-2)免疫荧光染色评估神经元损伤。利用电镜观察初级运动皮层M1区神经元超微结构。结果:左心室注射PRV 5.5天后在正常小鼠初级运动皮层M1区第五层(L5)观察到大量被标记的神经元。光遗传激活或抑制初级运动皮层M1区Glu能神经元,显著升高或降低心率变异性指标低频和高频功率比值(LF/HF)。与MI+Dio组比较,MI+taCsap3组血清NE含量、LF/HF功率比值以及心肌梗死边缘区TH、GAP43和NGF表达显著降低。与Sham组比较,MI组初级运动皮层M1区神经元MAP-2表达降低,Nissl小体密度降低,线粒体出现肿胀、分裂,嵴溶解等超微结构病理改变,c-Caspase3表达显著增加,TNF-α和IL-6表达增加,而有氧运动干预显著逆转该变化。与Sham组比较,MI组LF/HF功率比值显著升高,心肌NGF和TH分布面积、密度以及心肌胶原纤维显著增加,心功能降低,有氧运动干预显著逆转该变化。结论:由于支配心脏活动的神经元链与大脑初级运动皮层M1区Glu能神经元存在投射,抑制大脑初级运动皮层M1区Glu能神经元活动,显著改善心肌梗死后交感神经过度激活和心脏恶性重构。有氧运动可显著改善心肌梗死后大脑初级运动皮层M1区神经元损伤,抑制心交感神经恶性重构,改善心功能。提示,聚焦大脑初级运动皮层M1区神经调控与心脏保护,可能为未来研究无创治疗或预防心肌缺血损伤提供新的思路。

脑损伤患者额叶前皮质微结构MRI变化与认知功能损伤的相关性分析

目的 探讨脑损伤患者额叶前皮质微结构MRI变化与认知功能损伤的相关性。方法 选取2020年3月—2022年3月收治的脑损伤120例,根据有无认知功能损伤分为损伤组与无损伤组,每组60例;另选取60例体检健康者作为对照组。比较3组蒙特利尔认知评估量表(MoCA)各维度评分及总分,并比较有无认知功能损伤、不同认知功能损伤程度患者额叶前皮质微结构MRI变化[扩散各向异性分数(FA)、平均扩散率(MD)、轴向扩散峰度(AK)、平均扩散峰度(MK)、径向扩散峰度(RK)],分析额叶前皮质微结构MRI变化与认知功能损伤程度的相关性。结果 损伤组视空间与执行、注意力与计算力、语言功能、抽象能力、延迟记忆领域评分及MoCA总分低于无损伤组、对照组(P<0.01);损伤组前、旁扣带脑回右侧FA、AK及MK低于无损伤组(P<0.01);轻度认知功能损伤患者前、旁扣带脑回右侧FA、AK及MK高于中重度认知功能损伤患者(P<0.01);右侧FA、AK及MK与认知功能损伤程度呈负相关(P<0.01)。结论 脑损伤患者额叶前皮质微结构MRI变化可用于早期评估认知功能损伤,为临床评估脑损伤患者认知功能受损程度提供依据,利于针对性展开后续治疗,改善预后。

定向运动员的空间认知优势及脑加工特征研究

为考察定向运动练习能否提升练习者的空间认知能力,研究采用“专家—新手”范式,通过功能性近红外光谱成像(fNIRS)技术,比较不同水平定向运动员在心理旋转任务中的反应时、正确率、前额叶脑区血氧(Oxy-Hb)激活。结果发现:(1)与新手组相比,专家组的正确率更高,反应时更短;(2)与新手组相比,专家组在背外侧前额叶(R-DLPFC)、额极区(FOA)、腹外侧前额叶(VLPFC)的脑血氧激活强度更低。结论:定向运动练习改变了运动员的空间认知加工模式,提高了神经资源的利用效率,对认知功能的改善也起到了重要作用。

脑电波定量指数、MRS影像学DLPFC代谢物指标与抑郁症严重程度的相关性及联合检测对抑郁症疗效的预测价值

目的探讨脑电波定量指数C3、T3、FP1、F3、F7各频段的(δ+θ)/(α+β)值及磁共振波谱(MRS)影像学双侧背外侧前额叶皮质(DLPFC)代谢物指标的胆碱(Cho)/肌酸(Cr)、N-乙酰天门冬氨酸(NAA)/Cr、肌醇(MI)/Cr比值与抑郁症严重程度的相关性及联合检测对抑郁症疗效的预测价值。方法选取郑州市第八人民医院2022年1月至2023年1月收治的236例抑郁症患者作为抑郁症组,依据病情严重程度分为轻、中、重度抑郁,另选同期236例健康体检者为对照组,均进行定量脑电图检查与MRS检查,比较两组脑电波定量指数C3、T3、FP1、F3、F7各频段的(δ+θ)/(α+β)值及MRS-DLPFC代谢物Cho/Cr、NAA/Cr、MI/Cr比值,分析各指标与抑郁症患者严重程度的相关性及各指标联合检测对抑郁症疗效的预测价值。结果抑郁症组各频段(δ+θ)/(α+β)值均高于对照组,轻度抑郁患者各频段(δ+θ)/(α+β)值<中度抑郁<重度抑郁(P<0.05);抑郁症组双侧DLPFC代谢物NAA/Cr低于对照组,Cho/Cr高于对照组,轻度抑郁患者NAA/Cr>中度抑郁>重度抑郁,轻度抑郁患者Cho/Cr<中度抑郁<重度抑郁(P<0.05);抑郁症严重程度与各频段(δ+θ)/(α+β)值、双侧Cho/Cr呈正相关,与双侧NAA/Cr呈负相关(P<0.05);有效抑郁症患者各频段(δ+θ)/(α+β)值、双侧Cho/Cr均小于无效患者,双侧NAA/Cr大于无效患者(P<0.05);脑电波定量指数各频段(δ+θ)/(α+β)值及MRS-DLPFC代谢物Cho/Cr、NAA/Cr联合检测预测抑郁症患者疗效的AUC为0.900。结论脑电波定量指数各频段(δ+θ)/(α+β)值及MRS-DLPFC代谢物Cho/Cr、NAA/Cr均与抑郁症患者严重程度密切相关,且联合检测对抑郁症疗效具有较高的预测价值。