偏头痛患者脑白质损害的MRI特征

目的探讨偏头痛患者脑白质损害的MRI特征。方法对80例偏头痛患者(偏头痛组)及80例健康体检者(对照组)进行MRI检查。对结果进行比较分析。结果 MRI检查显示偏头痛组中有42例脑白质损害,表现为皮质下脑白质内等T1、长T2信号影,T2Flair高信号;对照组中有9例脑白质损害。偏头痛组脑白质损害的比例(52.5%)明显高于对照组(11.3%)(χ2=31.34,P0.01)。偏头痛组中有先兆偏头痛患者脑白质损害的比例(68.6%,24/35)明显高于无先兆偏头痛患者(40.0%,18/45)(χ2=15.58,P0.01)。结论偏头痛患者脑白质损害的MRI表现与其它原因引起的脑白质病变类似。偏头痛患者脑白质损害的发生率较高,且有先兆偏头痛者较无先兆偏头痛者更高。     

In vivo characterization of emerging white matter microstructure in the fetal brain in the third trimester

The third trimester of pregnancy is a period of rapid development of fiber bundles in the fetal white matter. Using a recently developed motion‐tracked slice‐to‐volume registration (MT‐SVR) method, we aimed to quantify tract‐specific developmental changes in apparent diffusion coefficient (ADC), fractional anisotropy (FA), and volume in third trimester healthy fetuses. To this end, we reconstructed diffusion tensor images from motion corrected fetal diffusion magnetic resonance imaging data. With an approved protocol, fetal MRI exams were performed on healthy pregnant women at 3 Tesla and included multiple (2–8) diffusion scans of the fetal head (1–2 b = 0 s/mm² images and 12 diffusion‐sensitized images at b = 500 s/mm²). Diffusion data from 32 fetuses (13 females) with median gestational age (GA) of 33 weeks 4 days were processed with MT‐SVR and deterministic tractography seeded by regions of interest corresponding to 12 major fiber tracts. Multivariable regression analysis was used to evaluate the association of GA with volume, FA, and ADC for each tract. For all tracts, the volume and FA increased, and the ADC decreased with GA. Associations reached statistical significance for: FA and ADC of the forceps major; volume and ADC for the forceps minor; FA, ADC, and volume for the cingulum; ADC, FA, and volume for the uncinate fasciculi; ADC of the inferior fronto‐occipital fasciculi, ADC of the inferior longitudinal fasciculi; and FA and ADC for the corticospinal tracts. These quantitative results demonstrate the complex pattern and rates of tract‐specific, GA‐related microstructural changes of the developing white matter in human fetal brain.     

Extent of altered white matter in unilateral and bilateral periventricular white matter lesions in children with unilateral cerebral palsy

AimsTo investigate the extent of white matter damage in children with unilateral cerebral palsy (UCP) caused by periventricular white matter lesions comparing between unilateral and bilateral lesions; and to investigate a relationship between white matter microstructure and hand function.Methods and proceduresDiffusion MRI images from 46 children with UCP and 18 children with typical development (CTD) were included. Subjects were grouped by side of hemiparesis and unilateral or bilateral lesions. A voxel-wise white matter analysis was performed to identify regions where fractional anisotropy (FA) was significantly different between UCP groups and CTD; and where FA correlated with either dominant or impaired hand function (using Jebsen Taylor Hand Function Test).Outcomes and resultsChildren with unilateral lesions had reduced FA in the corticospinal tract of the affected hemisphere. Children with bilateral lesions had widespread reduced FA extending into all lobes. In children with left hemiparesis, impaired hand function correlated with FA in the contralateral corticospinal tract. Dominant hand function correlated with FA in the posterior thalamic radiations as well as multiple other regions in both left and right hemiparesis groups.Conclusions and implicationsPeriventricular white matter lesions consist of focal and diffuse components. Focal lesions may cause direct motor fibre insult resulting in motor impairment. Diffuse white matter injury is heterogeneous, and may contribute to more global dysfunction.What this paper adds

• ⿢Focal white matter alterations are observed in the corticospinal tract in UCP with unilateral white matter lesions
• ⿢Diffuse white matter alterations throughout all cerebral lobes are observed in UCP with bilateral white matter lesions
• ⿢Fractional anisotropy in the posterior thalamic radiations correlates with dominant hand function

     

急性脑梗死患者脑白质病变因素风险评估

目的探讨脑白质病变对急性脑梗死患者预后的影响。方法选择驻马店市中心医院收治的282例急性脑梗死患者,根据MRI检查结果分为脑白质病变组(115例)和无脑白质病变组(167例),对2组临床资料(性别、年龄、糖尿病、高血压、房颤、高血脂)情况进行统计,同时对全部患者随访90d,评价患者的预后情况。结果脑白质病变组和无脑白质病变组男女比例及平均年龄差异无统计学意义(P0.05)。而脑白质病变组糖尿病、高血压、房颤、高血脂的发生率及预后不良率、病死率显著高于无脑白质病变组(P0.01)。结论急性脑梗死患者若在影像学检查中发现脑白质病变,需对相关危险因素进行积极干预,可有效改善预后,降低病死率。     

Heritability and genetic correlation between the cerebral cortex and associated white matter connections

The aim of this study is to investigate the genetic influence on the cerebral cortex, based on the analyses of heritability and genetic correlation between grey matter (GM) thickness, derived from structural MR images (sMRI), and associated white matter (WM) connections obtained from diffusion MRI (dMRI). We measured on sMRI the cortical thickness (CT) from a large twin imaging cohort using a surface‐based approach (N = 308, average age 22.8 ± 2.3 SD). An ACE model was employed to compute the heritability of CT. WM connections were estimated based on probabilistic tractography using fiber orientation distributions (FOD) from dMRI. We then fitted the ACE model to estimate the heritability of CT and FOD peak measures along WM fiber tracts. The WM fiber tracts where genetic influence was detected were mapped onto the cortical surface. Bivariate genetic modeling was performed to estimate the cross‐trait genetic correlation between the CT and the FOD‐based connectivity of the tracts associated with the cortical regions. We found some cortical regions displaying heritable and genetically correlated GM thickness and WM connectivity, forming networks under stronger genetic influence. Significant heritability and genetic correlations between the CT and WM connectivity were found in regions including the right postcentral gyrus, left posterior cingulate gyrus, right middle temporal gyri, suggesting common genetic factors influencing both GM and WM. Hum Brain Mapp 37:2331–2347, 2016. © 2016 Wiley Periodicals, Inc.     

不同程度脑白质病变对腔隙性梗死患者认知功能的影响

目的分析腔隙性梗死(LI)脑白质病变(WML)程度与认知功能的相关性。方法以30例LI无WML者为对照组,30例LI合并轻度WML者为轻度组,30例LI合并中度WML者为中度组,30例LI合并WML者为重度组,分析4组认知功能及WML程度与认知功能的相关性。结果 4组间各项MMSE评分、MMSE总评分、各项MoCA评分及MoCA总评分比较,差异有统计学意义(P0.05),均以重度组最低,对照组最高。同时,WML程度与MMSE总评分及MoCA总评分存在负向直线相关性(P0.05)。结论 LI患者WML程度与认知功能存在显著的相关性,可用于评估患者认知功能。     

Fibre orientation atlas guided rapid segmentation of white matter tracts

Fibre tract delineation from diffusion magnetic resonance imaging (MRI) is a valuable clinical tool for neurosurgical planning and navigation, as well as in research neuroimaging pipelines. Several popular methods are used for this task, each with different strengths and weaknesses making them more or less suited to different contexts. For neurosurgical imaging, priorities include ease of use, computational efficiency, robustness to pathology and ability to generalise to new tracts of interest. Many existing methods use streamline tractography, which may require expert neuroimaging operators for setting parameters and delineating anatomical regions of interest, or suffer from as a lack of generalisability to clinical scans involving deforming tumours and other pathologies. More recently, data-driven approaches including deep-learning segmentation models and streamline clustering methods have improved reproducibility and automation, although they can require large amounts of training data and/or computationally intensive image processing at the point of application. We describe an atlas-based direct tract mapping technique called ‘tractfinder’, utilising tract-specific location and orientation priors. Our aim was to develop a clinically practical method avoiding streamline tractography at the point of application while utilising prior anatomical knowledge derived from only 10–20 training samples. Requiring few training samples allows emphasis to be placed on producing high quality, neuro-anatomically accurate training data, and enables rapid adaptation to new tracts of interest. Avoiding streamline tractography at the point of application reduces computational time, false positives and vulnerabilities to pathology such as tumour deformations or oedema. Carefully filtered training streamlines and track orientation distribution mapping are used to construct tract specific orientation and spatial probability atlases in standard space. Atlases are then transformed to target subject space using affine registration and compared with the subject's voxel-wise fibre orientation distribution data using a mathematical measure of distribution overlap, resulting in a map of the tract's likely spatial distribution. This work includes extensive performance evaluation and comparison with benchmark techniques, including streamline tractography and the deep-learning method TractSeg, in two publicly available healthy diffusion MRI datasets (from TractoInferno and the Human Connectome Project) in addition to a clinical dataset comprising paediatric and adult brain tumour scans. Tract segmentation results display high agreement with established techniques while requiring less than 3 min on average when applied to a new subject. Results also display higher robustness than compared methods when faced with clinical scans featuring brain tumours and resections. As well as describing and evaluating a novel proposed tract delineation technique, this work continues the discussion on the challenges surrounding the white matter segmentation task, including issues of anatomical definitions and the use of quantitative segmentation comparison metrics.     

Structural white matter abnormalities in patients with idiopathic dystonia

We investigated whether structural white matter abnormalities, in the form of disruption of axonal coherence and integrity as measured with diffusion tensor imaging (DTI), constitute an underlying pathological mechanism of idiopathic dystonia (ID), independent of genotype status. We studied seven subjects with ID: all had cervical dystonia as their main symptom (one patient also had spasmodic dysphonia and two patients had concurrent generalized dystonia, both DYT1‐negative). We compared DTI MR images of patients with 10 controls, evaluating differences in mean diffusivity (MD) and fractional anisotropy (FA). ID was associated with increased FA values in the thalamus and adjacent white matter, and in the white matter underlying the middle frontal gyrus. ID was also associated with increase in MD in adjacent white matter to the pallidum and putamen bilaterally, left caudate, and in subcortical hemispheric regions, including the postcentral gyrus. Abnormal FA and MD in patients with ID indicate that abnormal axonal coherence and integrity contribute to the pathophysiology of dystonia. These findings suggest that ID is not only a functional disorder, but also associated with structural brain changes. Impaired connectivity and disrupted flow of information may contribute to the impairment of motor planning and regulation in dystonia. © 2006 Movement Disorder Society     

Age-related white matter lesions are associated with reduction of the apparent diffusion coefficient in the cerebellum

Cerebellar apparent diffusion coefficient (ADC) was found to be increased after acute cerebral hemispheric stroke. There are no data on cerebellar ADC changes in patients with chronic, age-related white matter lesions (ARWML). We aimed to determine longitudinal ADC variations on cerebral hemispheric and cerebellar white matter regions of patients with ARWML in order to study relations between ADC changes in both regions. ADC was measured serially (1-year interval) on lesioned periventricular frontal white matter, frontal and parietoccipital normal appearing white matter and middle cerebellar peduncles, on 19 aged patients with ARWML, which also underwent gait assessment. We compared regional ADC at 0 and 1 year and calculated variation percentages for each region. Correlation analysis was made between ADC variation in cerebellar regions and in contralateral hemispheric regions and between cerebellar ADC at 1 year and walking speed. After 1 year, ADC was higher on lesioned periventricular frontal white matter and lower on cerebellar regions. ADC variations on these regions were negatively correlated. Cerebellar ADC measured after 1 year was positively correlated with walking speed. This suggests a link between vascular disease progression inside frontal lesions and ADC reduction in contralateral cerebellar peduncles. Chronic ischemia in frontal white matter could have interrupted frontal-cerebellar circuits, producing hypometabolism in cerebellar regions (and worse performance on motor tasks), decreased perfusion and hence ADC reduction.     

The effect of hypointense white matter lesions on automated gray matter segmentation in multiple sclerosis

Previous imaging studies assessing the relationship between white matter (WM) damage and matter (GM) atrophy have raised the concern that Multiple Sclerosis (MS) WM lesions may affect measures of GM volume by inducing voxel misclassification during intensity‐based tissue segmentation. Here, we quantified this misclassification error in simulated and real MS brains using a lesion‐filling method. Using this method, we also corrected GM measures in patients before comparing them with controls in order to assess the impact of this lesion‐induced misclassification error in clinical studies. We found that higher WM lesion volumes artificially reduced total GM volumes. In patients, this effect was about 72% of that predicted by simulation. Misclassified voxels were located at the GM/WM border and could be distant from lesions. Volume of individual deep gray matter (DGM) structures generally decreased with higher lesion volumes, consistent with results from total GM. While preserving differences in GM volumes between patients and controls, lesion‐filling correction revealed more lateralised DGM shape changes in patients, which were not evident with the original images. Our results confirm that WM lesions can influence MRI measures of GM volume and shape in MS patients through their effect on intensity‐based GM segmentation. The greater effect of lesions at increasing levels of damage supports the use of lesion‐filling to correct for this problem and improve the interpretability of the results. Volumetric or morphometric imaging studies, where lesion amount and characteristics may vary between groups of patients or change over time, may especially benefit from this correction. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

脑白质损害的认知功能研究

目的 :观察脑白质损害 (WML )与事件相关电位 P30 0变化关系 ,探讨 WML在认知功能降低中的作用。方法 :35例经 MRI证实的 WML ,进行影像学、简易智能状态检测 (MMSE)和事件相关电位 P30 0测定 ,依据 WML体积将其分为轻度 (<5 cm3)、中度 (5～ 15 cm3)和重度 (>15 cm3) ,并对 WML与 P30 0潜伏期变化进行相关分析。结果 :轻度 WML 11例 ,中度 17例 ,重度 7例 ,主要表现为 T2和质子密度加权像上高信号 ,分布在脑室周围、半卵园中心及皮层下白质。轻度及中度 WML时 MMSE测定值无降低 ,重度 WML时 MMSE也只降低为 2 6 .9。随 WML的程度加重 ,P30 0潜伏期延长越明显 ,相关分析提示两者具有正相关。结论 :观察老年性 WML主要依靠 T2像或质子密度加权像。MMSE在反应 WML导致的认知功能障碍时不够敏感。 WML能引起事件相关电位 P30 0延长 ,其损害程度与 P30 0潜伏期变化呈正相关。     

Mild cognitive impairment in Parkinson's disease is associated with a distributed pattern of brain white matter damage

This study assesses the patterns of gray matter (GM) and white matter (WM) damage in patients with Parkinson's disease and mild cognitive impairment (PD‐MCI) compared with healthy controls and cognitively unimpaired PD patients (PD‐Cu). Three‐dimensional T1‐weighted and diffusion tensor (DT) magnetic resonance imaging (MRI) scans were obtained from 43 PD patients and 33 healthy controls. Cognition was assessed using a neuropsychological battery. Tract‐based spatial statistics was applied to compare DT MRI indices between groups on a voxel‐by‐voxel basis. Voxel‐based morphometry was performed to assess GM atrophy. Thirty PD patients were classified as MCI. Compared with healthy controls, PD‐Cu and PD‐MCI patients did not have GM atrophy. No region of WM damage was found in PD‐Cu patients when compared with healthy controls. Relative to healthy controls and PD‐Cu patients, PD‐MCI patients showed a distributed pattern of WM abnormalities in the anterior and superior corona radiata, genu, and body of the corpus callosum, and anterior inferior fronto‐occipital, uncinate, and superior longitudinal fasciculi, bilaterally. Subtle cognitive decline in PD is associated with abnormalities of frontal and interhemispheric WM connections, and not with GM atrophy. DT MRI might contribute to the identification of structural changes in PD‐MCI patients prior to the development of dementia. Hum Brain Mapp 35:1921–1929, 2014. © 2013 Wiley Periodicals, Inc.     

Hippocampal changes and white matter lesions in early-onset depression.

BACKGROUND: Hippocampal volume reduction and increased prevalence of subcortical white matter lesions have been reported in late-life depression. We aimed to examine whether total number of subcortical white matter lesions were associated with reduced hippocampal volume in aged female subjects with early-onset depression (< 45 years) and healthy comparison subjects. METHODS: The study included 28 middle-aged and elderly subjects with major depression and 41 age-matched control subjects. Hippocampal, parahippocampal gyrus, and orbitofrontal cortex volumes were determined using manual tracing methods. White matter lesions were rated from T2-weighted MRI scans using a semiquantitative classification scale. RESULTS: After controlling for total brain volume and age, patients had reduced hippocampal volume due to right hippocampal volume decrease (2.84 mL vs. 3.12 mL, F = 16.6, p < .001). Parahippocampal and orbitofrontal volumes did not differ significantly between groups. Multiple linear regression analysis indicated that reduced hippocampal volume did not significantly correlate with total number of subcortical white matter lesions (t = .673, p = .518). CONCLUSIONS: Right hippocampal volume was reduced in aged female early-onset subjects with depression. Total number of subcortical white matter lesions was not associated with the decrease in right hippocampal volume. Our data suggest hippocampal involvement, independent of subcortical white matter lesions, in the neuropathology of early-onset depression.     

3D tract‐specific local and global analysis of white matter integrity in Alzheimer's disease

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive decline in memory and other aspects of cognitive function. Diffusion‐weighted imaging (DWI) offers a non‐invasive approach to delineate the effects of AD on white matter (WM) integrity. Previous studies calculated either some summary statistics over regions of interest (ROI analysis) or some statistics along mean skeleton lines (Tract Based Spatial Statistic [TBSS]), so they cannot quantify subtle local WM alterations along major tracts. Here, a comprehensive WM analysis framework to map disease effects on 3D tracts both locally and globally, based on a study of 200 subjects: 49 healthy elderly normal controls, 110 with mild cognitive impairment, and 41 AD patients has been presented. 18 major WM tracts were extracted with our automated clustering algorithm—autoMATE (automated Multi‐Atlas Tract Extraction); we then extracted multiple DWI‐derived parameters of WM integrity along the WM tracts across all subjects. A novel statistical functional analysis method—FADTTS (Functional Analysis for Diffusion Tensor Tract Statistics) was applied to quantify degenerative patterns along WM tracts across different stages of AD. Gradually increasing WM alterations were found in all tracts in successive stages of AD. Among all 18 WM tracts, the fornix was most adversely affected. Among all the parameters, mean diffusivity (MD) was the most sensitive to WM alterations in AD. This study provides a systematic workflow to examine WM integrity across automatically computed 3D tracts in AD and may be useful in studying other neurological and psychiatric disorders. Hum Brain Mapp 38:1191–1207, 2017. © 2016 Wiley Periodicals, Inc.     

Associations between T1 white matter lesion volume and regional white matter microstructure in aging

White matter lesions, typically manifesting as regions of signal intensity abnormality (WMSA) on MRI, increase in frequency with age. However, the role of this damage in cognitive decline and disease is still not clear, as lesion volume has only loosely been associated with clinical status. Diffusion tensor imaging (DTI) has been used to examine the quantitative microstructural integrity of white matter, and has applications in the examination of subtle changes to tissue that appear visually normal on conventional imaging. The primary goal of this study was to determine whether major macrostructural white matter damage, (total WMSA volume), is associated with microstructural integrity of normal appearing white matter, and if these macrostructural changes fully account for microstructural changes. Imaging was performed in 126 nondemented individuals, ages 43–85 years, with no history of cerebrovascular disease. Controlling for age, greater WMSA volume was associated with decreased fractional anisotropy (FA) in widespread brain regions. Patterns were similar for FA and radial diffusivity but in contrast, WMSA was associated with axial diffusivity in fewer areas. Age was associated with FA in several regions, and many of these effects remained even when controlling for WMSA volume, suggesting the etiology of WMSAs does not fully account for all age‐associated white matter deterioration. These results provide evidence that WMSA volume is associated with the integrity of normal‐appearing white matter. In addition, our results suggest that overt lesions may not account for the association of increasing age with decreased white matter tissue integrity. Hum Brain Mapp 35:1085–1100, 2014. © 2013 Wiley Periodicals, Inc.     

Altered white matter connectivity in never‐medicated patients with schizophrenia

Numerous diffusion tensor imaging (DTI) studies have implicated white matter brain tissue abnormalities in schizophrenia. However, the vast majority of these studies included patient populations that use antipsychotic medication. Previous research showed that medication intake can affect brain morphology and the question therefore arises to what extent the reported white matter aberrations can be attributed to the disease rather than to the use of medication. In this study we included 16 medication‐naïve patients with schizophrenia and compared them to 23 healthy controls to exclude antipsychotic medication use as a confounding factor. For each subject DTI scans and magnetization transfer imaging (MTI) scans were acquired. A new tract‐based analysis was used that combines fractional anisoptropy (FA), mean diffusivity (MD) and magnetization transfer ratio (MTR) to examine group differences in 12 major white matter fiber bundles. Significant group differences in combined FA, MD, MTR values were found for the right uncinate fasciculus and the left arcuate fasciculus. Additional analysis revealed that the largest part of both tracts showed an increase in MTR in combination with an increase in MD for patients with schizophrenia. We interpret these group‐related differences as disease‐related axonal or glial aberrations that cannot be attributed to antipsychotic medication use. Hum Brain Mapp 34:2353–2365, 2013. © 2012 Wiley Periodicals, Inc.     

腔隙性脑梗死脑白质病变与脑微出血的相关性研究

目的探讨腔隙性脑梗死(LI)患者脑白质病变(WML)表现与脑微出血(CMBs)的关系。方法回顾性分析我院129例LI患者临床资料,根据CMBs病情程度将患者分为无出血组(n=20)、轻度组(n=60)、中度组(n=37)及重度组(n=12)。比较不同分组患者一般资料和实验室检测指标水平,分析CMBs与脑白质病变量表评分(WMLs)的相关性,采用Logistic多因素分析法分析LI患者WML和CMBs合并发病的相关因素。结果不同CMBs病情程度患者年龄和高血压合并症发生情况比较,差异有统计学意义(P<0.05)。不同CMBs病情程度患者血清HDL-C、LDL-C、hs-CRP、Hcy、CIMT及颈动脉斑块积分水平比较,差异均有统计学意义(P<0.05)。Logistic多因素回归分析显示,年龄、高血压、HDL-C、Hcy及CIMT是影响LI患者WML与CMBs合并发病的独立危险因素(P<0.05)。结论LI患者WML严重程度与CMBs病变程度呈正相关,年龄增长、高血压史、低水平HDL-C、高水平Hcy及CIMT增加是影响LI患者WML与CMBs合并发病的独立危险因素。     

腔隙性脑梗死脑白质病变与脑微出血的相关性研究

目的探讨腔隙性脑梗死(LI)患者脑白质病变(WML)表现与脑微出血(CMBs)的关系。方法回顾性分析我院129例LI患者临床资料,根据CMBs病情程度将患者分为无出血组(n=20)、轻度组(n=60)、中度组(n=37)及重度组(n=12)。比较不同分组患者一般资料和实验室检测指标水平,分析CMBs与脑白质病变量表评分(WMLs)的相关性,采用Logistic多因素分析法分析LI患者WML和CMBs合并发病的相关因素。结果不同CMBs病情程度患者年龄和高血压合并症发生情况比较,差异有统计学意义(P<0.05)。不同CMBs病情程度患者血清HDL-C、LDL-C、hs-CRP、Hcy、CIMT及颈动脉斑块积分水平比较,差异均有统计学意义(P<0.05)。Logistic多因素回归分析显示,年龄、高血压、HDL-C、Hcy及CIMT是影响LI患者WML与CMBs合并发病的独立危险因素(P<0.05)。结论LI患者WML严重程度与CMBs病变程度呈正相关,年龄增长、高血压史、低水平HDL-C、高水平Hcy及CIMT增加是影响LI患者WML与CMBs合并发病的独立危险因素。     

Minocycline attenuates white matter damage in a rat model of chronic cerebral hypoperfusion

White matter lesions are thought to result from chronic cerebral ischemia and constitute a core pathology of subcortical vascular dementia. This rarefaction has been known to be associated with microglial activation. We investigated whether minocycline, a microglial inhibitor, attenuates the white matter damage induced by chronic cerebral hypoperfusion that is used as a model of vascular dementia. Male Wistar rats were subjected to bilateral, permanent occlusion of the common carotid arteries (BCCAO) to induce chronic cerebral hypoperfusion. Minocycline or saline was injected daily for 2 weeks after BCCAO. In the corpus callosum and the optic tract, white matter damage observed with Klüver-Barrera staining was significantly attenuated in the minocycline-treated group compared to saline-treated controls. In control rats, immunoreactivities of major basic protein (MBP), Ox-42 as a microglial marker, and matrix metalloproteinase (MMP)-2 were increased in the corpus callosum. Minocycline significantly reduced these changes. Co-expression of Ox-42 and MMP-2 was confirmed by double immunofluorescence histochemistry. Our results suggest that chronic treatment with minocycline could be protective against at least some ischemic white matter damage, and its mechanism may be related to suppressing microglial activation.