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PI3K/AKT signaling and neuroprotection in ischemic stroke:molecular mechanisms and therapeutic perspectives

Neural Regeneration Research 2025年第10期20卷 2758-2775页

作者： Tianlong Liu Xiaolin Li Xiaowei Zhou Wei Chen Aidong Wen Minna Liu Yi Ding department of Pharmacy Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina department of Pharmacy The 940 Hospital of Joint Logistics Support Forces of Chinese PLALanzhouGansu ProvinceChina department of Pharmacy The 944 Hospital of Joint Logistics Support Forces of Chinese PLAJiuquanGansu ProvinceChina department of Nephrology The 940 Hospital of Joint Logistics Support Forces of Chinese PLALanzhouGansu ProvinceChina

It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic *** a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from *** article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling *** key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic *** investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.

关键词： apoptosis autophagy inflammation ischemic stroke neuroprotection oxidative stress pathogenesis phosphatidylinositol 3-kinase protein kinase B therapeutics

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Pancreatic primitive neuroectodermal tumors:Clinical features,treatment,and influencing factors

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World Journal of Gastrointestinal Oncology 2025年第2期17卷 230-245页

作者： Yan-Fei He Huan-Zhi Wang Xiao-Dong Hu Jun-Qiang Liu Hu-Ming Li Jie Wang Shuang-Feng Lu Health Management Center The Sixth Medical CenterChinese PLA General HospitalBeijing 100048China College of Atmospheric Sciences Lanzhou UniversityLanzhou 730000Gansu ProvinceChina department of Endocrinology The Sixth Medical CenterChinese PLA General HospitalBeijing 100048China department of Thoracic Surgery The Sixth Medical CenterChinese PLA General HospitalBeijing 100048China department of Respiratory Medicine The Sixth Medical CenterChinese PLA General HospitalBeijing 100048China

BACKGROUND Data on clinical characteristics,treatment outcomes,and prognosis of pancreatic primitive neuroectodermal tumors(PNETs)are *** To analyze the clinical data of 30 patients with pancreatic PNETs to identify their clinical characteristics and factors associated with *** We used the keywords"primary neuroectodermal tumor,""digestive tract,""pancreas,""pancreatic,"and"gastrointestinal,"individually or in combination,to collect data from a global database for all patients with pancreatic PNET to *** and Cox regression analyses were performed to identify prognostic factors for patient *** A total of 30 cases of pancreatic PNET were included in this study:15 males and 15 females with a mean age of 24 *** main symptom was abdominal pain(73.3%),and the median tumor size was 7.85 ***-four patients(80.0%)underwent surgery and nineteen patients received adjuvant *** metastasis was observed in 13 patients(43.3%),lymph node metastasis in 10 patients(33.3%),and distant metastasis in 6 patients(20.0%).Local recurrence was observed in 13 patients(43.3%).The median survival time of all patients was 29.4 months,and the overall estimated 1-year and 3-year survival rates were approximately 66.0%and 36.4%,*** analysis showed that chemotherapy(P=0.036),local metastasis(P=0.041),lymph node metastasis(P=0.003),distant metastasis(P=0.049),and surgical margins(P=0.048)were the prognostic factors affecting *** analysis revealed only lymph node metastasis(P=0.012)as a prognostic *** Pancreatic PNET is extremely rare,occurs in young adults,has no apparent sex predisposition,has a high rate of metastasis and early recurrence,and has a very poor *** diagnosis of pancreatic PNET requires a combination of clinical symptoms,pathologic features,immunohistochemistry,and cytogenetic *** analysis suggested that chemotherapy,metastasis,and surgical ma

关键词： Primitive neuroectodermal tumor Pancreas Sarcoma Diagnosis Prognosis Treatment

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Stir-Fried Semen Armeniacae Amarum Suppresses Aristolochic AcidⅠ-Induced Nephrotoxicity and DNA Adducts

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Chinese Journal of Integrative Medicine 2025年第2期31卷 142-152页

作者： LI Cheng-xian XIAO Xiao-he LI Xin-yu XIAO Da-ke WANG Yin-kang WANG Xian-ling ZHANG Ping LI Yu-rong NIU Ming BAI Zhao-fang School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing(100102)China department of Hepatology Military Institute of Chinese Materiathe Fifth Medical CentreGeneral Hospital of PLABeijing(100039)China National Key Laboratory of Kidney Beijing(100039)China School of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu(610075)China School of Traditional Chinese Medicine Capital Medical UniversityBeijing(100069)China School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou(510515)China department of Pharmacy Medical Supplies Center of PLA General HospitalBeijing(100039)China department of Military Patient Management the Fifth Medical Center of PLA General HospitalBeijing(100039)China department of Hematology the Fifth Medical Center of Chinese PLA General HospitalBeijing(100071)China

Objective:To investigate the protective effects of stir-fried Semen Armeniacae Amarum(SAA)against aristolochic acidⅠ(AAⅠ)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et ***:In vitro,HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3(MRP3)were constructed by Lentiviral transduction,and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening *** m RNA,protein expressions,and enzyme activity levels of NAD(P)H quinone dehydrogenase 1(NQO1)and cytochrome P4501A2(CYP1A2)were measured in differentiated Hepa RG *** toxicity after inhibition of AAⅠmetabolite transport was detected using cell counting kit-8 *** vivo,C57BL/6 mice were randomly divided into 5 groups according to a random number table,including:control(1%sodium bicarbonate),AAⅠ(10 mg/kg),stir-fried SAA(1.75 g/kg)and AAⅠ+stir-fried SAA(1.75 and 8.75 g/kg)groups,6 mice in each *** 7 days of continuous gavage administration,liver and kidney damages were assessed,and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined ***:In vivo,combination of 1.75 g/kg SAA and 10 mg/kg AAⅠsuppressed AAⅠ-induced nephrotoxicity and reduced d A-ALI formation by 26.7%,and these detoxification effects in a dose-dependent manner(P<0.01).Mechanistically,SAA inhibited MRP3 transport in vitro,downregulated NQO1 expression in vivo,increased CYP1A2 expression and enzymatic activity in vitro and in vivo,respectively(P<0.05 or P<0.01).Notably,SAA also reduced AAⅠ-induced hepatotoxicity throughout the detoxification process,as indicated by a 41.3%reduction in the number of liver adducts(P<0.01).Conclusions:Stirfried SAA is a novel drug candidate for the suppression of AAⅠ-induced liver and kidney dam

关键词： aristolochic acidⅠ stir-fried Semen Armeniacae Amarum detoxification principles of compatibility metabolic enzymes transporters

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Monitoring of urinary iodine concentration in naval pilots:should iodine be supplemented or limited at coastal stations?

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Military Medical Research 2025年第1期12卷 154-156页

作者： Jia Zeng Qi Li Xiang Lu Dan-Dan Liu Rong-Guan Jiao Yan-Qing Jiang Yan-Bing Liu Wan-Qing Xu Jun Ma Guo-Li Gu department of Aeronautical Diseases Naval Medical CenterNaval Medical University of Chinese PLAShanghai 200052China No.92853 Station Troops hospital of Chinese pla Huludao 125000LiaoningChina department of Intensive Care Unit Naval Medical CenterNaval Medical University of Chinese PLAShanghai 200052China department III of Internal Medicine Naval Medical CenterNaval Medical University of Chinese PLAShanghai 200052China department of General Surgery Air Force Medical CenterAir Force Medical University of Chinese PLABeijing 100142China

Dear Editor,In recent years,there has been a significant upward trend in the detection rate of thyroid diseases among military flight personnel[1].Thyroid diseases not only pose a serious threat to the health of flight personnel but also have negative impacts on the aviation safety and combat effectiveness of *** has been confirmed that the occurrence and progression of thyroid diseases are closely linked to dietary iodine *** have manifested that long-term excessive or insufficient iodine intake can lead to thyroid diseases[2,3].

关键词： Naval pilot Thyroid Urinary iodine

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A novel flexible nerve guidance conduit promotes nerve regeneration while providing excellent mechanical properties

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Neural Regeneration Research 2025年第7期20卷 2084-2094页

作者： Tong Li Quhan Cheng Jingai Zhang Boxin Liu Yu Shi Haoxue Wang Lijie Huang Su Zhang Ruixin Zhang Song Wang Guangxu Lu Peifu Tang Zhongyang Liu Kai Wang department of Orthopedics the Fourth Medical Center of Chinese PLA General HospitalBeijingChina department of Training and Sports Medicine Characteristic Medical Center of Chinese People’s Armed Police ForceTianjinChina Medical School of Chinese pla BeijingChina Key Laboratory of Bioactive Materials for the Ministry of Education College of Life SciencesNankai UniversityTianjinChina department of Orthopedics Tianjin HospitalTianjinChina department of Rehabilitation Medicine Er Quan Hospital of PAPWuxiJiangsu ProvinceChina

Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor *** an alternative,nerve guidance conduits may be *** ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve *** designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align ***,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber *** presence of aligned fibers on the inner surface can promote the extension of nerve cells along the *** helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide *** novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.

关键词： aligned fibers anti-kinking helical fibers nerve guidance conduit nerve regeneration peripheral nerve injury topological guidance

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Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

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Neural Regeneration Research 2025年第5期20卷 1416-1430页

作者： Mou Gao Qin Dong Dan Zou Zhijun Yang Lili Guo Ruxiang Xu department of Neurosurgery Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina department of Neurosurgery Chinese PLA General HospitalBeijingChina department of Neurology Fu Xing HospitalCapital Medical UniversityBeijingChina

Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and *** previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological ***,the mechanism of CXCR4 upregulation in induced neural stem cells remains *** this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 ***,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial *** agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury ***,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head *** conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neura

关键词： Akt signaling cerebral edema closed head injury Crry CXCR4 induced neural stem cell microglia neuroinflammation

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Biomaterial‑based mechanical regulation facilitates scarless wound healing with functional skin appendage regeneration

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Military Medical Research 2025年第1期12卷 96-120页

作者： Ying-Ying Li Shuai-Fei Ji Xiao-Bing Fu Yu-Feng Jiang Xiao-Yan Sun Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research department Chinese PLA General Hospital and PLA Medical CollegePLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin InjuryRepair and RegenerationResearch Unit of Trauma CareTissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing 100048China Research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing 100048China 2Department of Tissue Regeneration and Wound RepairChinese PLA General HospitalBeijing 100853China

Scar formation resulting from burns or severe trauma can significantly compromise the structural integrity of skin and lead to permanent loss of skin appendages,ultimately impairing its normal physiological *** evidence underscores the potential of targeted modulation of mechanical cues to enhance skin regeneration,promoting scarless repair by influencing the extracellular microenvironment and driving the phenotypic *** field of skin repair and skin appendage regeneration has witnessed remarkable advancements in the utilization of biomaterials with distinct physical ***,a comprehensive understanding of the underlying mechanisms remains somewhat elusive,limiting the broader application of these *** this review,we present two promising biomaterial-based mechanical approaches aimed at bolstering the regenerative capacity of compromised *** first approach involves leveraging biomaterials with specific biophysical properties to create an optimal scarless environment that supports cellular activities essential for *** second approach centers on harnessing mechanical forces exerted by biomaterials to enhance cellular plasticity,facilitating efficient cellular reprogramming and,consequently,promoting the regeneration of skin *** summary,the manipulation of mechanical cues using biomaterial-based strategies holds significant promise as a supplementary approach for achieving scarless wound healing,coupled with the restoration of multiple skin appendage functions.

关键词： Scarless Wound healing Biomaterials Mechanical cues Skin appendages

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FSD1 inhibits glioblastoma diffuse infiltration through restriction of HDAC6-mediated microtubule deacetylation

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Science China Life Sciences 2025年第03期 673-688页

作者： Dake Xiao Haowen Ran Lishu Chen Yuanyuan Li Yan Cai Songyang Zhang Qinghui Qi Huiran Wu Cheng Zhang Shuailiang Cao Lanjuan Mi Haohao Huang Ji Qi Qiuying Han Haiqing Tu Huiyan Li Tao Zhou Fangye Li Ailing Li Jianghong Man Nanhu Laboratory National Center of Biomedical Analysis School of Traditional Chinese Medicine Capital Medical University department of Neurosurgery General Hospital of Central Theater Command of Chinese PLA School of Life and Health Sciences Huzhou College department of Neurosurgery Beijing Fengtai Hospital department of Neurosurgery First Medical Center of PLA General Hospital

The infiltration of glioblastoma multiforme(GBM) is predominantly characterized by diffuse spread, contributing significantly to therapy resistance and recurrence of GBM. In this study, we reveal that microtubule deacetylation, mediated through the downregulation of fibronectin type III and SPRY domain-containing 1(FSD1), plays a pivotal role in promoting GBM diffuse infiltration. FSD1 directly interacts with histone deacetylase 6(HDAC6) at its second catalytic domain, thereby impeding its deacetylase activity on α-tubulin and preventing microtubule deacetylation and depolymerization. This inhibitory interaction is disrupted upon phosphorylation of FSD1 at its Ser317 and Ser324 residues by activated CDK5, leading to FSD1 dissociation from microtubules and facilitating HDAC6-mediated α-tubulin deacetylation. Furthermore, increased expression of FSD1 or interference with FSD1 phosphorylation reduces microtubule deacetylation, suppresses invasion of GBM stem cells, and ultimately mitigates tumor infiltration in orthotopic GBM xenografts. Importantly, GBM tissues exhibit diminished levels of FSD1 expression, correlating with microtubule deacetylation and unfavorable clinical outcomes in GBM patients. These findings elucidate the mechanistic involvement of microtubule deacetylation in driving GBM cell invasion and offer potential avenues for managing GBM infiltration.

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Overexpression of Parkin promotes the protective effect of mitochondrial autophagy on the lung of rats with exertional heatstroke

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重症医学（英文） 2025年第1期5卷 89-99页

作者： Meng Ran Sun Zhengzhong Chi Ruxue Gu Yan Zhang Yuxiang Wang Jiaxing Graduate School of Hebei North University Zhangjiakou Hebei China department of Critical Care Medicine The Eighth Medical Center of Chinese PLA General Hospital Beijing China

Background::The roles of the Pink1/Parkin pathway and mitophagy in lung injury during heat stroke remain unclear. In this study, we investigated the role of Pink1/Parkin-mediated mitophagy in acute lung injury (ALI) in rats with exertional heat stroke (EHS).Methods::Sixty Sprague Dawley rats were randomly divided into control (CON), control + Parkin overexpression (CON + Parkin), EHS, and EHS + Parkin overexpression (EHS + Parkin) groups. Parkin was overexpressed by injecting an adeno-associated virus carrying the Parkin gene into the tail vein, and a rat model of EHS was established. Pathological changes in the lung tissue were analyzed using microcomputed tomography (micro-CT), and the lung coefficient and pulmonary capillary permeability were measured. Enzyme-linked immunosorbent assay were used to determine the levels of interleukin-6 (IL-6), IL-1 β, and tumor necrosis factor- α, and reactive oxygen species. The morphology of mitochondria in type Ⅱ epithelial cells of lung tissue was observed using transmission electron microscopy;and the apoptosis of lung tissue, the level of mitophagy, and the co-localization of Pink1 and Parkin were determined using immunofluorescence. The expression of Pink1, Parkin, mitofusin-2 (MFN2), phosphatase and tensin homolog (PTEN), PTEN-L, p62, and the autophagy marker microtubule-associated protein 1 light chain 3 (LC3) in rat lung tissue was measured by Western blotting, and the ratio of LC3II/LC3I was calculated. Results::Compared with the EHS group, the survival rate of rats in the EHS + Parkin group was significantly higher. Their lung coefficient and pulmonary vascular permeability decreased and the pathological changes were significantly alleviated ( P <0.05). Their levels of inflammatory factors and reactive oxygen species were significantly decreased ( P <0.05), and the degree of mitochondrial swelling in pulmonary type II epithelial cells was alleviated. The apoptosis of lung tissue wa

关键词： Exertional heat stroke Acute lung injury Mitophagy Pink1 Parkin

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High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

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Neural Regeneration Research 2025年第9期20卷 2611-2623页

作者： Mengshi Yang Miao Bai Yuan Zhuang Shenghua Lu Qianqian Ge Hao Li Yu Deng Hongbin Wu Xiaojian Xu Fei Niu Xinlong Dong Bin Zhang Baiyun Liu Beijing Tiantan hospital Capital Medical UniversityBeijingChina department of Neurology The First Hospital of Tsinghua UniversityBeijingChina department of Neurotrauma and Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina department of Critical Care Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Center for Nerve Injury and Repair Beijing Institute of Brain DisordersChina National Clinical Research Center for Neurological DiseasesBeijingChina

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently *** potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet *** the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of *** vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial ***,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were ***-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of *** Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our ***-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain *** dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in *** receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain ***,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is th

关键词： apoptosis BV2 microglia dexamethasone glucocorticoid receptor glucocorticoids innate immune system microglial polarization neuroinflammation primary microglia traumatic brain injury

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