Correlation of blood-brain barrier leakage with cerebral small vessel disease including cerebral microbleeds in Alzheimer's disease.

Background: Blood-brain barrier (BBB) damage is considered an important part of Alzheimer's disease (AD) progression, and cerebral small-vessel disease (CSVD) is commonly associated with AD. However, the relationship between BBB damage, small cerebrovascular lesions, especially cerebral microbleeds (CMBs), and amyloid and tau biomarkers remains controversial. Therefore, our study aimed to further investigate their association in our cohort of patients with AD. Methods: A total of 139 individuals were divided into probable AD (18F-florbetapir PET positive, n = 101) and control group (cognitively normal, n = 38). The levels of cerebrospinal fluid (CSF) and plasma t-tau, p-tau181, Aß40, Aß42, and albumin were measured using corresponding commercial assay kits, and the CSF/plasma albumin ratio (Qalb), an indicator of BBB dysfunction, was calculated. CSVD burden and the number of CMBs were defined using magnetic resonance imaging. Results: Patients with AD had higher Qalb (p = 0.0024), higher numbers of CMBs (p = 0.03), and greater CSVD burden (p < 0.0001). In the AD group, CMBs and CSVD correlated with a higher Qalb (p = 0.03), and the numbers of CMBs negatively correlated with CSF Aß42 (p = 0.02). Conclusion: Blood-brain barrier damage was accompanied by a more severe burden of CSVD, including CMB, in patients with AD.

Volume of White Matter Hyperintensities, and Cerebral Micro-Bleeds.

PURPOSE: In the past years the significance of white matter hyperintensities (WMH) has gained raising attention because it is considered a marker of severity of different pathologies. Another condition that in the last years has been assessed in the neuroradiology field is cerebral microbleeds (CMB). The purpose of this work was to evaluate the association between the volume of WMH and the presence and characteristics of CMB. MATERIAL AND METHODS: Sixty-five consecutive (males 45; median age 70) subjects were retrospectively analyzed with a 1.5 Tesla scanner. WMH volume was quantified with a semi-automated procedure considering the FLAIR MR sequences whereas the CMB were studied with the SWI technique and CMBs were classified as absent (grade 1), mild (grade 2; total number of CMBs: 1-2), moderate (grade 3; total number of CMBs: 3-10), and severe (grade 4; total number of CMBs: >10). Moreover, overall number of CMBs and the maximum diameter were registered. RESULTS: Prevalence of CMBs was 30.76% whereas WMH 81.5%. Mann-Whitney test showed a statistically significant difference in WMH volume between subjects with and without CMBs (p < 0.001). Pearson analysis showed significant correlation between CMB grade, number and maximum diameter and WMH. The better ROC area under the curve (Az) was obtained by the hemisphere volume with a 0.828 (95% CI from 0.752 to 0,888; SD = 0.0427; p value = 0.001). The only parameters that showed a statistically significant association in the logistic regression analysis were Hemisphere volume of WMH (p = 0.001) and Cholesterol LDL (p = 0.0292). CONCLUSION: In conclusion, the results of this study suggest the presence of a significant correlation between CMBs and volume of WMH. No differences were found between the different vascular territories.

The Relationship between Bleeding and Contrast Extravasation Judged by Dual Energy CT after Acute Thrombectomy.

Objective: There are many cases in which computed tomography (CT) after acute thrombectomy demonstrates high-density areas, but it may be difficult to judge whether this is hemorrhage or contrast extravasation. Dual energy CT (DECT) is an imaging method that enables discrimination of substances by acquiring X-ray image data of two different energies. Methods: We performed DECT to distinguish hemorrhage from contrast extravasation in cases with high-density areas on CT after acute thrombectomy at our hospital, and we compared with T2*-weighted image on the following day. Results: Six patients comprising 22 areas had high-density areas on CT after acute thrombectomy. In all, 20 of the 22 high-density areas were determined to be contrast extravasation by DECT, and no cases of subsequent symptomatic cerebral hemorrhage were observed. However, 11 areas with new microbleeds were confirmed in the 20 extravasation areas on MRI-T2* images the day after thrombectomy. Conclusion: This examination suggested that the contrast extravasation and its concentration are involved in the presence of low-intensity areas on T2*.

Perinatal Micro-Bleeds and Neuroinflammation in E19 Rat Fetuses Exposed to Utero-Placental Ischemia.

Offspring of preeclampsia patients have an increased risk of developing neurological deficits and cognitive impairment. While low placental perfusion, common in preeclampsia and growth restriction, has been linked to neurological deficits, a causative link is not fully established. The goal of this study was to test the hypothesis that placental ischemia induces neuroinflammation and micro-hemorrhages in utero. Timed-pregnant Sprague Dawley rats were weight-matched for sham surgery (abdominal incision only) or induced placental ischemia (surgical reduction of utero-placental perfusion (RUPP)); n = 5/group on gestational day 14. Fetal brains (n = 1-2/dam/endpoint) were collected at embryonic day (E19). Placental ischemia resulted in fewer live fetuses, increased fetal demise, increased hematocrit, and no difference in brain water content in exposed fetuses. Additionally, increased cerebral micro-bleeds (identified with H&E staining), pro-inflammatory cytokines: IL-1ß, IL-6, and IL-18, eotaxin (CCL11), LIX (CXCL5), and MIP-2 (CXCL2) were observed in RUPP-exposed fetuses. Microglial density in the sub-ventricular zone decreased in RUPP-exposed fetuses, with no change in cortical thickness. Our findings support the hypothesis that exposure to placental ischemia contributes to microvascular dysfunction (increased micro-bleeds), fetal brain inflammation, and reduced microglial density in proliferative brain areas. Future studies will determine whether in utero abnormalities contribute to long-term behavioral deficits in preeclampsia offspring through impaired neurogenesis regulation.

Topographic distribution of brain iron deposition and small cerebrovascular lesions in amyotrophic lateral sclerosis and in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates.

Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal lobar degeneration (FTLD) in 15% of the cases. A neuropathological continuity between ALS and FTLD-TDP is suspected. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) study compares the topographic distribution of iron (Fe) deposition and the incidence of small cerebrovascular lesions in ALS and in FTLD brains. Seventy-eight post-mortem brains underwent 7.0-tesla MRI. The patients consisted of 12 with ALS, 38 with FTLD, and 28 controls. Three ALS brains had minor FTLD features. Three coronal sections of a cerebral hemisphere were submitted to T2 and T2* MRI sequences. The amount of Fe deposition in the deep brain structures and the number of small cerebrovascular lesions was determined in ALS and the subtypes of FTLD compared to control brains, with neuropathological correlates. A significant increase of Fe deposition was observed in the claustrum, caudate nucleus, globus pallidus, thalamus, and subthalamic nucleus of the FTLD-FUS and FTLD-TDP groups, while in the ALS one, the Fe increase was only observed in the caudate and the subthalamic nuclei. White matter changes were only significantly more severe in the FTLD compared to those in ALS and in controls brains. Cortical micro-bleeds were increased in the frontal and temporal lobes of FTLD as well as of ALS brains compared to controls. Cortical micro-infarcts were, on the other hand, more frequent in the control compared to the ALS and FTLD groups. The present study supports the assumption of a neuropathological continuity between ALS and FTLD and illustrates the favourable vascular risk profile in these diseases.

Correlation between micro-bleeds and hemorrhagic transformation after ischemic stroke / 中国综合临床

Objective To investigate the correlation between micro?bleeds and hemorrhagic transformation( HT ) after ischemic stroke. Methods One hundred and forty?five cases patients with acute ischemic stroke who were admitted to Luhe Hospital of Beijing Affiliated to Capital Medical University from 2009 to 2014 were retrospective analyzed. The MBs T2??weighted gradient?echo MRI was performed within 48 hours after admission to examine if there was a micro?bleeds,and the incidence of HT was assessed using follow?up brain MRI or CT in 2 weeks after admission. There were 125 patients with stroke were in without HT group and 20 patients were in HT group. Results There were no significant differences in terms of MBs ( P=0. 170 ) , gender( P=0. 671 ) , age ( P=0. 528 ) , hypertension ( P=0. 597 ) , diabetes ( P=0. 571 ) , hyperlipidaemia ( P=0. 772),smoking(P=0. 672),history of stroke(P=0. 469),coagulation function(P=0. 527),antiplatelet(P=0. 642),anticoagulation(P=0. 611) in HT group and without HT group. Atrial fibrillation((45%(9/20) vs. 22%( 28/125 ) , P = 0. 034 ) , NIHSS score ( 10. 9 ± 0. 5 ) points vs. ( 7. 8 ± 1. 2 ) points, P<0. 001 ) , thrombolysis(20% (4/20) vs.5% (6/125),P = 0.015) have significant differences in two groups.In multivariate logistic regression analysis,atrial fibrillation( OR=2. 421,95%CI 1. 823-3. 256,P=0. 012) ,NIHSS score( OR=9. 303, 95%CI 3. 094-27. 970, P<0. 001 ) were independent predictors for HT after ischemic stroke. Conclusion There is no relationship between MBs and HT after ischemic stroke. Atrial fibrillation,the severe of stroke are independent predictors for HT after ischemic stroke.

Blood-Induced Joint Damage: The Devastating Effects of Acute Joint Bleeds versus Micro-Bleeds.

OBJECTIVE: Four days of blood exposure leads to irreversible cartilage damage in vitro. In contrast, intermittent intra-articular blood injections twice a week during 4 weeks (mimicking micro-bleeds) in a canine model resulted in transient damage only. In this study, it was evaluated whether acute joint bleeds are more harmful than micro-bleeds in a canine model of knee arthropathy. DESIGN: Seven dogs received 4 sequential daily intra-articular blood injections twice in 2 weeks (mimicking 2 acute 4-day joint bleeds). Seven other dogs received the same blood load but in a total of 8 injections intermittently over the 4-week period with at least 1 day in between (mimicking micro-bleeds over the same timespan). Contralateral knees served as controls. Ten weeks after the last injection cartilage matrix turnover and synovial inflammation were evaluated. RESULTS: Only after the acute joint bleeds the release of newly formed and total (resident) cartilage matrix glycosaminoglycans were increased (P = 0.04 and P = 0.01, respectively). Furthermore, in animals with the acute joint bleeds cartilage glycosaminoglycan content was decreased (P = 0.01) and not in animals with micro-bleeds. Mild synovial inflammation was observed in both groups (both P < 0.0001) but was not different between groups. CONCLUSIONS: In contrast to micro-bleeds, 2 acute joint bleeds lead to prolonged cartilage damage independent of the level of synovial inflammation. This model suggests that micro-bleeds are less devastating than acute joint bleeds with respect to joint damage, which might be of relevance to treatment of joint bleeds in clinical practice.