Dexmedetomidine Inhibits Hippocampal Neuronal Damage Caused by Persistent Isoflurane-Induced Hypotension in Rat Model of Chronic Cerebral Hypoperfusion.

Purpose The purpose of this study was to investigate the effect of dexmedetomidine (DEX) on hypotension-induced neuronal damage in a chronic cerebral hypoperfusion (CCH) model of rats, an established model of cerebral white matter lesions (WML) in humans, which is prevalent in the elderly and closely related to cognitive decline. Methods The CCH model rats were randomly assigned to one of four groups: normotension + no DEX (NN) group (n = 6), normotension + DEX (ND) group (n = 6), hypotension + no DEX (HN) group (n = 6), or hypotension + DEX (HD) group (n = 6). Under isoflurane anesthesia, mean arterial blood pressure was maintained at or above 80 mmHg (normotension) or below 60 mmHg (hypotension) for a duration of two hours. The DEX groups received 50 µg of DEX intraperitoneally. Two weeks later, the Y-maze test and, after preparing brain slices, immunohistochemical staining were performed using antibodies against neuronal nuclei (NeuN), microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adapter molecule 1 (Iba1). Results Behavioral observations showed no significant differences among the groups. Significant reductions of both NeuN-positive cells and the MAP2-positive area were found in the hippocampal CA1 in the HN group compared with NN and ND groups, but not in the HD group. GFAP and Iba-1-positive areas were significantly increased in the HN group, but not in the HD group. Conclusion DEX significantly ameliorated hypotension-induced neuronal damage and both astroglial and microglial activation in the CA1 region of CCH rats.

Pathogeneses and Imaging Features of Cerebral White Matter Lesions of Vascular Origins.

White matter lesion (WML), also known as white matter hyperintensities or leukoaraiosis, was first termed in 1986 to describe the hyperintense signals on T2-weighted imaging (T2WI) and fluid-attenuated inversion recovery (FLAIR) maps. Over the past decades, a growing body of pathophysiological findings regarding WMLs have been discovered and discussed. Currently, the generally accepted WML pathogeneses mainly include hypoxia-ischemia, endothelial dysfunction, blood-brain barrier disruption, and infiltration of inflammatory mediators or cytokines. However, none of them can explain the whole dynamics of WML formation. Herein, we primarily focus on the pathogeneses and neuroimaging features of vascular WMLs. To achieve this goal, we searched papers with any type published in PubMed from 1950 to 2020 and cross-referenced the keywords including "leukoencephalopathy", "leukoaraiosis", "white matter hyperintensity", "white matter lesion", "pathogenesis", "pathology", "pathophysiology", and "neuroimaging". Moreover, references of the selected articles were browsed and searched for additional pertinent articles. We believe this work will supply the robust references for clinicians to further understand the different WML patterns of varying vascular etiologies and thus make customized treatment.

Intracerebral hematoma expansion and intracranial internal carotid artery calcifications.

BACKGROUND AND AIMS: Prediction of intracerebral hematoma expansion (IHE) is of critical importance during intracerebral hemorrhage (ICH) management. Given its suggested positive connection with cerebral microvascular disease status, intracranial internal carotid artery wall calcifications (ICAC) on admission computed tomography (CT) studies may contribute to prediction of IHE. METHOD: Presence, burden and type [as per Kockelkoren's score] of ICAC were defined in admission CT and CT-angiography of 201 ICH patients [mean age: 70 ± 13 years, 44 % female]. A Kockelkoren's score of <7 indicated intimal calcification [iICAC], while ≥7 indicated non-intimal [or medial] ones [mICAC]. IHE criteria were absolute volume increase of ≥12.5cc or ≥6cc, and relative increase ≥33 % or ≥26 %. RESULT: ICAC was diagnosed in 79.6 % of ICH patients. ICAC status was not independent indicator of milder IHE (≥6cc and ≥26 % IHE, both in 27 %). Presence of contralateral mICAC was found to be an independent predictor for higher grade IHE (expß = 3.44, 95 %CI: 1.47-8.04, for IHE ≥ 12.5cc, diagnosed in 14.4 %; and expß = 2.67, 95 %CI: 1.29-5.55, for IHE ≥ 33 %, diagnosed in 24 %). Mortality (31 %) was higher in those with ipsilateral any type ICAC (36 % in mICAC, 38 % in iICAC, 17 % in no ICAC, p = 0.017), but this was not independent predictor in logistic regression. Similarly, medial ICAC in both ipsilateral (47 % vs. 31 %, p = 0.037) and contralateral (47 % vs. 30 %, p = 0.017) sides was associated with poorer prognosis (42 %) on univariate, but not multivariate analysis. CONCLUSION: Intracranial ICA calcification is highly prevalent in ICH. mICAC may be associated with risk of "high amount" acute hematoma expansion, hospital mortality and poor prognosis.

Impact of Cholinergic Pathway Damage on Cognitive Impairment Caused by Cerebral White Matter Lesions / 中国康复理论与实践

Objective To investigate the relationship between cholinergic pathway damage and the executive dysfunction of patients with different degrees of cognitive impairment caused by cerebral white matter lesions(WML). Methods From March,2016 to December,2017,115 patients were recruited,whose characteristics,such as age,gender, education,and history of hypertension,diabetes and stroke were recorded.According to the T2-weighted MRI,80 patients were defined as WML.WML patients were divided into cognitively normal(CN)group(n=41),vascular cognitive impairment of none dementia(VCIND)group(n=21)and vascular dementia(VaD)group(n=18)ac-cording to the result of Montreal Cognitive Assessment(MoCA)and Clinical Dementia Rating(CDR).Other 35 cases without WML and cognitive impairment were as control group.WML under MRI were evaluated with Cho-linergic Pathways Hyperintensities Scale(CHIPS).All the WML patients were assessed with Stroop Color-Word Test,Trail Making Test, Symbol Digital Modalities Test, and Verbal Fluence Test.The correlation between the scores of CHIPS and the executive tests were analysed. Results There was no significant difference in age, gender, level of education, and cardiovascular disease risk factors among four groups(P>0.05),but there were significant differences in scores of MoCA and CHIPS(F>25.781,P<0.001),while the score of MoCA was the least(P<0.01)and the scores of CHIPS were the most in VaD group (P<0.001).The CHIPS scores of left and bilateral hemisphere negatively correlated with all the scores of execu-tive tests(P<0.05),while that of the right hemisphere just correlated with the scores of some executive tests(P<0.05). Conclusion For cognitive impairment after WML,cholinergic pathway damage may relate with the executive function impairment,especially the damage in left cerebral hemisphere.

Influence of cerebral white matter lesions on the activities of daily living of older patients with mild stroke.

AIM: Neurological symptom severity is a prognostic factor for post-stroke activities of daily living (ADL). Recently, it has been reported that white matter lesions indicate poor functional prognosis in patients with stroke. The present study investigated the influence of white matter lesions on the ADL of older patients with stroke who have mild neurological symptoms. METHOD: We investigated ADL at discharge in 44 patients with stroke (men, n = 27; women, n = 17; mean age 78 years [range 71-85 years]) aged ≥65 years with National Institutes of Health Stroke Scale scores of ≤5 (cerebral infarction, n = 37; cerebral hemorrhage, n = 7). We used single correlation analysis and multiple regression analysis to investigate factors that correlated with ADL at discharge. ADL at discharge was also evaluated on the basis of white matter lesion severity (Fazekas classification, grades 0-3). RESULTS: Single correlation analysis showed that age (r = -0.36, P = 0.016), male sex (r = 0.362, P = 0.016), neurological symptom severity (r = -0.361, P = 0.016), ADL on starting rehabilitation (r = 0.685, P < 0.001) and white matter lesion severity (r = -0.361, P = 0.016) significantly correlated with ADL at discharge. Multiple regression analysis showed that ADL on starting rehabilitation (ß = 0.519, t = 4.723, P < 0.001) and white matter lesion severity (ß = -0.309, t = -3.057, P < 0.01) were statistically significant prognostic factors for ADL at discharge. ADL at discharge score was significantly lower in the group with high white matter lesion severity (Fazekas, grade 2) than in the other two groups (Fazekas, grade 0, P < 0.01; Fazekas, grade 1, P < 0.05). CONCLUSION: Severe white matter lesions are a prognostic factor for poor ADL at discharge in older patients with stroke who have mild neurological symptoms. Geriatr Gerontol Int 2016; 16: 942-947.

Analysis of an Association between Single Nucleotide Polymorphisms of Vascular Endothelial Growth Factor Gene and Risk of Cerebral White Matter Lesion

BACKGROUND: Endothelial dysfunction is suggested to be one of the pathogenesis of cerebral white matter lesion (cWML). Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and integrity of vascular endothelial cell, and altered expression of VEGF gene induces vascular diseases including cerebrovascular diseases. The objective of this study is to investigate whether single nucleotide polymorphism (SNP) of VEGF gene confers an increased risk of cWML. METHODS: Total 337 study subjects without history of stroke were included. The presence and severity of cWML were measured on fluid-attenuated inversion recovery image. Genotypes of VEGF -2578G>A, -1154G>A, -634G>C and +936C>T were analyzed. RESULTS: Among 337 study subjects, cWML was found in 208 patients (62%), and fifty-eight cases (17%) of them had overt cWML. In univariate analysis, age, female sex and plasma total homocysteine level (tHcyt) were higher in the mild and overt cWML group than no cWML group (p<0.05). The percentage of previous history of hypertension and the value of systolic blood pressure were higher in overt cWML group than no cWML group. In univariate and logistic regression analysis, none of four tested VEGF SNPs was significantly different between control group, mild and overt cWML groups. There was no difference between plasma tHcyt levels and each VEGF SNPs in control group and cWML groups. CONCLUSIONS: In this study, old age, female sex, hypertension and plasma tHcyt were associated with cWML. However, we failed to find an association between cWML and VEGF gene polymorphism, which may indicate that genetic polymorphism of VEGF does not play a direct role in the pathogenesis of cWML.

Association between Single Nucleotide Polymorphisms of alpha2A-, alpha2B-, and alpha2C-Adrenergic Receptor Genes and Risk of Cerebral White Matter Lesion / 대한뇌졸중학회지

BACKGROUND: An alpha2-adrenergic receptor (alpha2-AR, ADRA2) mediates induction of hypotension and inhibition of lipolysis and insulin secretion. We evaluated whether single nucleotide polymorphisms (SNPs) of alpha2A (ADRA2A), alpha2B (ADRA2B), and alpha2C (ADRA2C) adrenergic receptors are associated with cerebral white matter lesion (cWML). METHODS: Total 336 study subjects who had no stroke were enrolled in this study. The Indices of cWML include total WML (TWML), periventricular WML (PVWML), and subcortical WML (SCWML) on brain fluid-attenuated inversion recovery (FLAIR) image. Common genetic variants of ADRA2A (1780G>A), ADRA2B (Ins/Del301-303), and ADRA2C (Ins/Del322-325) were examined. RESULTS: Among 336 study subjects, cWML was found in 66 patients (20%). In multivariate analysis, there were no significant effects of all tested ADRA2 polymorphisms on TWML. Significant association of ADRA2A 1780 AA genotype was found in PVWML (OR: 3.368, 95% CIs: 1.280-8.865, adjusted p-value after false discovery rate (FDR) correction=0.014) but not SCWML. CONCLUSION: Although SNPs of three ADRA2 subtypes failed to reach a significance in overall risk for cWML, the ADRA2A 1780G>A polymorphism may be associated with development of PVWML.

Progress in Ischemic White Matter Lesions / 国际脑血管病杂志

Head MRI and CT scans Can frequently find ischemic cerebral white matter lesions in healthy elderly and in patients with atherosclerosis.Ischemic cerebral white matter lesions are regarded as a manifestation of cerebral small vessel lesions.which Can result in symptoms such as cognitive impairment,and predict extraeranial or intracranial ischemic events.This article reviews the recent progress in research on cerebral white matter lesions.their pathogenesis and clirilcal significance.