CCH引起血管性认知障碍的机制与干预新进展
Journal: Basic Medical Theory Research DOI: 10.12238/bmtr.v6i5.10070
Abstract
血管性认知障碍(VCI)包括从轻度认知障碍到痴呆的一系列认知缺陷。VCI严重影响患者的生活质量,已成为全球急需解决的公共卫生问题。由于血管病因的异质性和疾病神经病理学的复杂性,VCI的致病机制仍存在争议,最近对脑血流测量的临床研究支持慢性脑灌注不足(CCH)作为VCI血管病变和临床表现的主要驱动因素。本文就CCH诱导VCI所涉及的病理变化机制进行综述,总结了目前针对CCH致病机制的有效干预VCI进展的新发现。
Keywords
慢性脑灌注不足；神经元细胞死亡；血管性痴呆；白质病变
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[2] Duncombe J,Kitamura A,Hase Y,Ihara M,Kalaria RN,Horsbu rgh K. Chronic cerebral hypoperfusion: a key mechanism leadi ng to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia[J].Clin Sci(Lond).2017;131 (19):2451-2468.
[3] Fann DY,Lee SY,Manzanero S,Chunduri P,Sobey CG,Arumug am TV.Pathogenesis of acute stroke and the role of inflammaso mes[J].Ageing Res Rev.2013;12(4):941-966.
[4] T anović A, Alfaro V. Neuroproteccion con memantina (antagonista no competitivo del receptor NMDA-glutamato) frente a la excitotoxicidad asociada al glutamato en la enfermedad de Alzheimer y en la demencia vascular [Glutamate-related excitot oxicity neuroprotection with memantine,an uncompetitive antag onist of NMDA-glutamate receptor,in Alzheimer's disease and vasc ular dementia][J].Rev Neurol.2006;42(10):607-616.
[5] Xiong ZG,Zhu XM,Chu XP,etal.Neuroprotection in ischemia:blocking calcium-permeable acid-sensing ion channels [J].Cell. 2004;118(6):687-698.
[6] Tian D,Gao Q,Chang Z,Lin J,Ma D,Han Z.Network pharmacology and in vitro studies reveal the pharmacological effects and mole
[7] Liu H, Zhang J. Cerebral hypoperfusion and cognitive impairment: the pathogenic role of vascular oxidative stress [J].Int J Neurosci.2012;122(9):494-499.
[8] Faraci FM. Reactive oxygen species:influence on cerebral vascular tone[J].J Appl Physiol(1985).2006;100(2):739-743.
[9] Choi DH, Lee KH, Kim JH, etal.NADPH oxidase 1,a novel molecular source of ROS in hippocampal neuronal death in vascular dementia[J].Antioxid Redox Signal.2014;21(4):533-550.
[10] De Silva TM, Faraci FM. Microvascular Dysfunction and Cognitive Impairment[J].Cell Mol Neurobiol.2016;36(2):241-258.
[11] Barić D. Why pulsatility still matters: a review of current knowledge[J].Croat Med J.2014;55(6):609-620.
[12] Ahad MA, Chear NJ, Abdullah MH, et al. Effects of clitorienolactones from Clitoria ternatea root on calcium channel mediating hippocampal long-term potentiation in rats induced chronic cerebral hypoperfusion[J].Ageing Res Rev.2024;96:102252.
[13] Yamagishi S, Nakamura K, Matsui T. Role of oxidative stress in the development of vascular injury and its thera peutic intervention by nifedipine [J].Curr Med Chem. 2008;15(2):172-177.
[14] Saito A. Physiological functions of endoplasmic retic ulum stress transducer OASIS in central nervous system [J].Anat Sci Int.2014;89(1):11-20.
[15] Hetz C, Saxena S. ER stress and the unfolded protein response in neurodegeneration[J].Nat Rev Neurol. 2017;13(8):477-491.
[16] Liu S, Zhang X, Lin B, et al. Melastoma dodecandrum lour. Protects against cerebral ischemia-reperfusion injury by ameliorating oxidative stress and endoplasmic reticulum stress[J].J Ethnopharmacol.2025;336:118735.
[17] Fan LL,Fang H, Zheng JY, et al. Taohong Siwu decoction alleviates cognitive impairment by suppressing endoplasmic reticulum stress and apoptosis signaling pathway in vascular dementia rats [J].J Ethnopharmacol.2024;333:118407.
[18] Wang H, Liu Y, Cui M, et al. Pseudoginsenoside-F11 reduces cognitive impairment and white matter injury in vascular dementia by alleviating autophagy-lysosomal pathway deficiency[J].Phytomedicine.2024;133:155883.
[19] Baik SH, Selvaraji S, Fann DY, et al. Hippocampal transcriptome profiling reveals common disease pathways in chronic hypoperfusion andaging[J].Aging(Albany NY).2021;13 (11):14651-14674.
[20] Lejri I, Grimm A, Eckert A. Mitochondria, Estrogen and Female Brain Aging [J].Front Aging Neurosci. 2018;10:124. Published 2018 Apr27.
[21] Navarro A,Boveris A.The mitochondrial energy transdu ction system and the aging process[J].Am J Physiol Cell Phys iol.2007;292(2):C670-C686.
[22] Ding Q, Dimayuga E, Keller JN. Proteasome regulation of oxidative stress in aging and age-related diseases of the CNS[J].Antioxid Redox Signal.2006;8(1-2):163-172.
[23] Li X, Wen W, Li P, et al. Mitochondrial Protection and Against Glutamate Neurotoxicity via Shh/Ptch1 Signaling Pathway to Ameliorate Cognitive Dysfunction by Kaixin San in Multi-Infarct Dementia Rats[J].Oxid Med Cell Longev. 2021; 2021:5590745.
[24] Sun C,Liu M,Liu J,etal.ShenmaYizhi Decoction Improvesthe Mitochondrial Structure in the Brain and Ameliorates Cognitive Impairment in VCI Rats via the AMPK/UCP2 Signaling Pathway[J].Neuropsychiatr Dis Treat.2021;17:1937-1951.
[25] Poh L,Fann DY,Wong P,etal.AIM2 inflammasome mediates hallmark neuropathological alterations and cognitive impairm ent in a mouse model of vascular dementia [J]. Mol Psychiatry. 2021;26(8):4544-4560.
[26] Babcock AA, Kuziel WA, Rivest S, Owens T. Chemokine expression by glial cells directs leukocytes to sites of axonalinjury in the CNS[J].J Neurosci.2003;23(21):7922-7930.
[27] Zhang LY,Pan J,Mamtilahun M,etal.Microglia exacerbate white matter injury via complement C3/C3aR pathway after hypoperfusion[J].Theranostics.2020;10(1):74-90.
[28] Zhou Y,Zhang J,Wang L, et al. Interleukin-1β impedes oligodendrocyte progenitor cell recruitment and white matt er repair following chronic cerebral hypoperfusion [J]. Brain Behav Immun.2019 May;78:202-203.
[29] Zheng Y,Zhang J, Zhao Y,etal.Curcumin protects again st cognitive impairments in a rat model of chronic cerebral hypoperfusion combined with diabetes mellitus by suppressi ng neuroinflammation, apoptosis, and pyroptosis[J].Int Immun opharmacol.2021;93:107422.
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