Blood-brain barrier dysfunction in Binswanger’s disease; an immunohistochemical study

Binswanger’s disease is pathologically characterized by a combination of diffuse cerebrovascular white matter lesions and lacunar infarcts in the basal ganglia and white matter. Although a blood-brain barrier (BBB) dysfunction has been implicated in the pathogenesis of these white matter (WM) lesions, few authors have addressed this problem. In the present study, we describe BBB dysfunction and its regional differences in the brains of Binswanger’s disease patients. Twelve brains from Binswanger’s disease patients (group III) were examined and compared with those from five patients with non-neurological disease (group I) and five cortical infarct patients without significant WM lesions (group II). Immunohistochemistry was performed for glial fibrillary acidic protein and vimentin as astroglial cell markers, and for immunoglobulins, complements and fibrinogen as extravasated serum protein markers. The grading scores for IgG extravasation were significantly higher in group III as compared to group I, in both the periventricular WM and the subcortical WM (P < 0.01). In group III, the scores in the periventricular WM and subcortical WM were significantly higher than in the subcortical U fibers and cerebral cortex (P < 0.01 for the periventricular WM; P < 0.001 for the subcortical WM), respectively. Clasmatodendritic astroglia, which had swollen cell bodies and large cytoplasmic vacuoles with disintegrated processes, incorporated the serum components IgG, IgM, C3d, C1q and fibrinogen, both in the periventricular WM and subcortical WM in 5 out of 12 (42%) Binswanger’s disease brains. These results indicate that WM lesions in Binswanger’s disease are accompanied by BBB dysfunction, although it remains uncertain whether BBB dysfunction is secondary to either chronic cerebral ischemia or arterial hypertension. Received: 25 April 1997 / Revised, accepted: 21 July 1997     

Magnetization Transfer and T2 Relaxation Components in Tissue

T₂ relaxation makes an important contribution to tissue contrast in magnetic resonance (MR) imaging. Many tissues are known to exhibit multicomponent T₂ relaxation that suggests some compartmental segregation of mobile protons on a T₂ timescale. Magnetization transfer (MT) is another relaxation mechanism that can be used to produce tissue contrast in MR imaging. The MT process depends strongly on water-macromolecular interactions. To investigate the relationship between multicomponent T₂ relaxation and the MT process, multiecho T₂ measurements have been combined with MT measurements for freshly excised samples of cardiac muscle, striated muscle, and white matter. For muscle, short T₂ components show greater MT than long T₂ components, consistent with the belief that they represent distinct water environments. For white matter, quantitative MT measurements were identical for the two major T₂ components, apparently because of exchange between the T₂ compartments on a timescale characteristic of the MT experiment. Implications for accurate modeling of MT in tissue and the use of MT for MR image contrast are discussed.     

Magnetization transfer imaging of multiple sclerosis

While conventional magnetic resonance imaging (MRI) measures signal primarily from the hydrogen nuclei of water, magnetization transfer (MT) MRI indirectly detects macromolecular associated hydrogen nuclei via their magnetic interaction with the observable water. In the normal adult CNS, white matter exhibits the largest MT effect due to the macromolecular content of the highly structured and lipid rich myelin. Pathologies which alter the structural integrity and the relative macromolecular-water composition, such as multiple sclerosis (MS), therefore show abnormal MT. Conventional MRI, which has a high MS lesion detection sensitivity but poor specificity in terms of differentiating the pathological state of a plaque, can thus be supplemented by MT to provide more specific information on the extent of demyelination and axonal loss. In this paper we review the basic concepts of MT imaging and its role in MS lesion characterization.Financial support was provided by the Medical Research Council of Canada, Fonds de la Recherche en Santé du Québec, and the Killam Foundation.     

Leukoencephalopathy with swelling in children and adolescents: MRI patterns and differential diagnosis

In children, several neurological disorders are characterised by spongiform leukoencephalopathy. MRI of the brain typically shows white matter swelling, but does not enable differentiation of the various underlying disorders. The aim of this article is optimisation of the diagnostic value of MRI in leukoencephalopathy accompanied by swelling. MRI-based inclusion criteria were met by 20 patients in our database. The images were analysed using a detailed scoring list. In 13 of the 20 patients the clinical diagnosis was known (11 definite and 2 probable diagnoses). Characteristic MRI abnormalities could be defined in these patients. Of the 7 patients without a diagnosis, 5 had identical MRI abnormalities: difuse hemisphere swelling and typical cysts in frontoparietal subcortical white matter and the tips of the temporal lobes. The clinical picture was also similar in these patients, suggesting a similar disease.     

Biexponential diffusion tensor analysis of human brain diffusion data.

Several studies have shown that in tissues over an extended range of b-factors, the signal decay deviates significantly from the basic monoexponential model. The true nature of this departure has to date not been identified. For the current study, line scan diffusion images of brain suitable for biexponential diffusion tensor analysis were acquired in normal subjects on a clinical MR system. For each of six noncollinear directions, 32 images with b-factors ranging from 5 to 5000 s/mm2 were collected. Biexponential fits yielded parameter maps for a fast and a slow diffusion component. A subset of the diffusion data, consisting of the images obtained at the conventional range of b-factors between 5 and 972 s/mm2, was used for monoexponential diffusion tensor analysis. Fractional anisotropy (FA) of the fast-diffusion component and the monoexponential fit exhibited no significant difference. FA of the slow-diffusion biexponential component was significantly higher, particularly in areas of lower fiber density. The principal diffusion directions for the two biexponential components and the monoexponential solution were largely the same and in agreement with known fiber tracts. The second and third diffusion eigenvector directions also appeared to be aligned, but they exhibited significant deviations in localized areas.     

北京市区大气细菌粒子的沉降量

本工作用平皿沉降法在北京市西单观测了大气细菌粒子的沉降量。结果表明,大气细菌粒子的年平均沉降量为72.9个/皿·5min;一天内大气细菌粒子沉降量出现7:00、19:00两个高峰时和13:00、夜间1:00两个低峰时。同时表明,大气细菌粒子的沉降量夏季高,冬季低;白天高,夜间低。     

White matter damage precedes that in gray matter despite similar magnetic resonance imaging changes following cerebral hypoxia-ischemia in neonatal rats

We hypothesized that the cerebral injury produced by hypoxia-ischemia (HI) in neonatal rats would differ in white compared with gray matter as detected histologically or with magnetic resonance (MR) imaging methods. Maps of T₂ and the apparent diffusion coefficient (ADC) of water were acquired in 1-week-old rats at times prior to cerebral HI (right carotid artery occlusion plus 1.5 h of hypoxia), within the last 5–10 min of HI, and 1 h or 24 h after HI. Near the end of HI, ADC decreased and T₂ increased in both cortical gray and subcortical white matter within the cingulum of the HI hemisphere. One hour after HI, ADC partially recovered, but T₂ remained increased and then increased further by 24 h post-HI. In contrast to the similar MR responses in white and gray matter, histological evidence for irreversible cell damage occurred in white matter earlier than in gray matter within the HI hemisphere. At 1 h post-HI, rarefied or disrupted nerve fibers and an increase in TUNEL-positive cells were observed within white matter in the cingulum, whereas neurons within the cortical gray matter appeared normal. By 24 h post-HI, damage was apparent in both white and gray matter. Thus, MR imaging detected acute tissue edema following cerebral HI in both gray and white matter but did not distinguish between the early irreversible tissue injury detected histologically in white but not gray matter in this rather severe model of neonatal encephalopathy.     

大鼠大脑白质及白质内有髓神经纤维的性别与年龄差异

目的:研究正常年轻和中老年组雌雄性大鼠大脑白质及白质内有髓神经纤维之间的性别差异,并探讨大脑发育过程中性别差异随年龄增加的改变。方法:运用透射电子显微镜和体视学方法对6~8月龄的年轻Long-Evans大鼠及18月龄同种中老年大鼠大脑白质及其有髓神经纤维进行定量研究。结果:年轻组雄性大鼠大脑白质、有髓神经纤维及其髓鞘的总体积均显著大于雌性,而中老年组雌性大鼠大脑白质、有髓神经纤维体积密度、有髓神经纤维及其髓鞘的总体积均显著大于雄性。结论:年轻组及中老年组大鼠大脑白质、白质内有髓神经纤维及其髓鞘总体积均存在性别差异,随着年龄的增长,雄性大鼠大脑白质及白质内有髓神经纤维体积的减少较雌性更为明显。     

Genotoxicity and physicochemical characteristics of traffic-related ambient particulate matter

Exposure to ambient particulate matter (PM) has been linked to several adverse health effects. Since vehicular traffic is a PM source of growing importance, we sampled total suspended particulate (TSP), PM(10), and PM(2.5) at six urban locations with pronounced differences in traffic intensity. The mutagenicity, DNA-adduct formation, and induction of oxidative DNA damage by the samples were studied as genotoxicological parameters, in relation to polycyclic aromatic hydrocarbon (PAH) levels, elemental composition, and radical-generating capacity (RGC) as chemical characteristics. We found pronounced differences in the genotoxicity and chemical characteristics of PM from the various locations, although we could not establish a correlation between traffic intensity and any of these characteristics for any of the PM size fractions. Therefore, the differences between locations may be due to local sources of PM, other than traffic. The concentration of total (carcinogenic) PAHs correlated positively with RGC, direct and S9-mediated mutagenicity, as well as the induction of DNA adducts and oxidative DNA damage. The interaction between total PAHs and transition metals correlated positively with DNA-adduct formation, particularly from the PM(2.5) fraction. RGC was not associated with one specific PM size fraction, but mutagenicity and DNA reactivity after metabolic activation were relatively high in PM(10) and PM(2.5), when compared with TSP. We conclude that the toxicological characteristics of urban PM samples show pronounced differences, even when PM concentrations at the sample sites are comparable. This implies that emission reduction strategies that take chemical and toxicological characteristics of PM into account may be useful for reducing the health risks associated with PM exposure.