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Clinical management of cerebral small vessel disease:a call for a holistic approach

Chinese Medical Journal 2021年第2期134卷 127-142页

作者： Una Clancy Jason P.Appleton carmen arteaga Fergus N.Doubal Philip M.Bath Joanna M.Wardlaw Centre for Clinical Brain Sciences and UK Dementia Research InstituteUniversity of EdinburghChancellor's Building49 Little France CrescentEdinburghEH164SPUK Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottingham NG51PBUK Stroke University Hospitals Birmingham NHS Foundation TrustMindelsohn WayEdgbastonBirmingham B152GWUK Stroke Nottingham University Hospitals NHS TrustNottingham NG51PBUK.

Cerebral small vessel disease(SVD)is a common global brain disease that causes cognitive impairment,ischemic or hemorrhagic stroke,problems with mobility,and neuropsychiatric symptoms.The brain damage,seen as focal white and deep grey matter lesions on brain magnetic resonance imaging(MRI)or computed tomography(CT),typically accumulates"covertly"and may reach an advanced state before being detected incidentally on brain scanning or causing symptoms.Patients have typically presented to different clinical services or been recruited into research focused on one clinical manifestation,perhaps explaining a lack of awareness,until recently,of the full range and complexity of SVD.In this review,we discuss the varied clinical presentations,established and emerging risk factors,relationship to SVD features on MRI or CT,and the current state of knowledge on the effectiveness of a wide range of pharmacological and lifestyle interventions.The core message is that effective assessment and clinical management of patients with SVD,as well as future advances in diagnosis,care,and treatment,will require a more"joined-up"’approach.This approach should integrate clinical expertise in stroke neurology,cognitive,and physical dysfunctions.It requires more clinical trials in order to improve pharmacological interventions,lifestyle and dietary modifications.A deeper understanding of the pathophysiology of SVD is required to steer the identification of novel interventions.An essential prerequisite to accelerating clinical trials is to improve the consistency,and standardization of clinical,cognitive and neuroimaging endpoints.

关键词： Dementia Magnetic resonance imaging Mild cognitive impairment Risk factors Small vessel disease Stroke Symptoms Treatment

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Added after Anoxia-Reoxigenation Stress, Genistein Rescues from Death the Rat Embryo Cortical Neurons

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Neuroscience & Medicine 2010年第2期1卷 50-59页

作者： Arce carmen arteaga José Luis Sánchez-mendoza Eduardo Oset Gasque Ma Jesús González Ma Pilar Centro de Investigaciones Biológicas CSIC Ramiro de Maeztu Madrid Spain Department of Biochemistry and Molecular Biology Faculty of Pharmacy Universidad Complutense Madrid Spain

Estrogens and phytoestrogens have neuroprotective effect against neuronal damage induced by cerebral ischemia /reperfusion (I/R) injury. In preceding studies, the phytoestrogen effects have been assessed by administration previous to the ischemic period, conditions which are unusual to apply to the treatment of human stroke. Here we present a study on neuroprotection afforded by genistein on rat embryo cortical neurons subjected to oxygen and glucose deprivation (OGD) followed by re-oxigenation, when added after the stress stimulus. At 1 and 2 h of OGD times and after 24 h of reperfusion, cell viability, necrotic, apoptotic and autophagic cell death and different parameters related to oxidative stress and mitochondrial dysfunction were measured in the absence and presence of 1 μM genisteine. We found an in-creasing loss of neuronal viability after 1-5 h of OGD which was only reversed in part by 24 h of reperfusion. These changes were preceded by increases in ROS generation, caspase-3 activation, LDH release and increase in LC3B lipi-dation, indicative of autophagia. Treatment with 1 μM genistein during the 24 h reperfusion significantly attenuated neuronal necrosis and autophagia induced by 1 and 2 h of OGD exposure. Genistein also decreased ROS generation and lipid-peroxidation induced by 2 h of OGD. These results suggest an important neuroprotective effect of genistein against transient post-ischemic-like

关键词： Cortical Neurons Oxygen-glucose Deprivation Brain Ischemia Neuronal Death Necrosis Apoptosis Autophagy

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