Cerebrospinal fluid nitrite/nitrate predicts poor outcome in patients with subarachnoid hemorrhage (SAH)

NAAG, an agonist at Group II metabotropic glutamate receptors and at the N-methyl- d -aspartate (NMDA)-type of ionotropic glutamate receptor, was infused at 250 nmoles in 0.25 μL of saline into each cerebral ventricle of 12-day-old rat pups. Proportion of pycnotic neurons was determined in 100 × 200 μm areas of medial and lateral blades of DG, and in areas CA1, CA3a, b of both dorsal and ventral hippocampus. In some sections we used Fluoro-JADE-B staining to visualize degenerating neuronal cell bodies. There was a marked neurodegeneration, particularly in the medial blade of DG, at 24 h after the administration of NAAG but it was lower at the 4-day time point. No significant damage was observed in 50-day-old rat. The results indicate that early postnatal administration of NAAG can cause serious loss of neurons in rat hippocampus.
Acknowledgement:  Supported by LNOOB122 MEYS CR.     

Correlation of F4-neuroprostanes levels in cerebrospinal fluid with outcome of aneurysmal subarachnoid hemorrhage in humans

Aneurysmal subarachnoid hemorrhage (aSAH) is one type of hemorrhagic stroke in humans. F₂-isoprostanes (F₂-IsoPs) and F₄-neuroprostanes (F₄-NPs), derived from arachidonic acid and docosahexaenoic acid (DHA), respectively, are specific markers of lipid peroxidation. We previously demonstrated that F₂-IsoPs levels in cerebrospinal fluid (CSF) of aSAH patients positively correlated with poor clinical conditions. In this work, we refined F₄-NPs analysis and investigated the role of potential oxidative damage to neurons in aSAH patients by detecting F₄-NPs in CSF. [²H₄]-15-F_2t-IsoP, rather than [¹⁸O₂]-17-F_4c-NP or [²H₄]-PGF_2α, was used as the internal standard for F₄-NPs analysis. One problem of the use of [¹⁸O₂]-17-F_4c-NP was the potential interference resulting from F₂-dihomo-IsoPs in CSF. CSF specimens of 15 aSAH patients for up to 10 days and those of 12 non-aSAH controls were analyzed. First day, mean, and peak levels of F₄-NPs were all significantly higher in aSAH patients than in controls and correlated with the Fisher Scale and 3-month Glasgow Outcome Scale, but only mean levels of F₄-NPs correlated with Hunt and Hess Grade. The results first demonstrate oxidative damage to DHA in brain tissue following aSAH and suggest that F₄-NPs in CSF could be a better predictor for outcome of aSAH than F₂-IsoPs at early time points.     

Angiopoietin-1 is associated with cerebral vasospasm and delayed cerebral ischemia in subarachnoid hemorrhage

Background  

Angiopoietin-1 (Ang-1) and -2 (Ang-2) are keyplayers in the regulation of endothelial homeostasis and vascular proliferation. Angiopoietins may play an important role in the pathophysiology of cerebral vasospasm (CVS). Ang-1 and Ang-2 have not been investigated in this regard so far.     

A case report of delayed cortical infarction adjacent to sulcal clots after traumatic subarachnoid hemorrhage in the absence of proximal vasospasm

Background

Cortical ischemic lesions represent the predominant pathomorphological pattern of focal lesions after aneurysmal subarachnoid hemorrhage (aSAH). Autopsy studies suggest that they occur adjacent to subarachnoid blood and are related to spasm of small cortical rather than proximal arteries. Recent clinical monitoring studies showed that cortical spreading depolarizations, which induce cortical arterial spasms, are involved in lesion development. If subarachnoid blood induces adjacent cortical lesions, it would be expected that (i) they also develop after traumatic subarachnoid hemorrhage (tSAH), and (ii) lesions after tSAH can occur in absence of angiographic vasospasm, as was found for aSAH.

Case presentation

An 86-year-old woman was admitted to our hospital with fluctuating consciousness after hitting her head during a fall. The initial computed tomography (CT) was significant for tSAH in cortical sulci. On day 8, the patient experienced a secondary neurological deterioration with reduced consciousness and global aphasia. Whereas the CT scan on day 9 was still unremarkable, magnetic resonance imaging (MRI) on day 10 revealed new cortical laminar infarcts adjacent to sulcal blood clots. Proximal vasospasm was ruled out using MR and CT angiography and Doppler sonography. CT on day 14 confirmed the delayed infarcts.

Conclusions

We describe a case of delayed cortical infarcts around sulcal blood clots after tSAH in the absence of proximal vasospasm, similar to results found previously for aSAH. As for aSAH, this case suggests that assessment of angiographic vasospasm is not sufficient to screen for risk of delayed infarcts after tSAH. Electrocorticography is suggested as a complementary method to monitor the hypothesized mechanism of spreading depolarizations.

     

An in vitro model of aneurysmal subarachnoid hemorrhage: oxidation of unconjugated bilirubin by cytochrome oxidase

Aneurysmal subarachnoid hemorrhage is a stroke subtype with high rates of mortality and morbidity. Cerebral vasospasm can lead to ischemic injury or death and is a common complication of aneurysmal subarachnoid hemorrhage, usually occurring 3-9 days afterwards. The cause of vasospasm is not known. Recently, there has been strong evidence that vasoactive oxidation products of bilirubin may be involved. Currently, the factors that lead to bilirubin oxidation are poorly characterized. In this study, we have designed an in vitro model of hemorrhagic stroke in order to investigate conditions that promote the oxidation of bilirubin to form vasoactive compounds. Using our model, we created a basic hematoma system of blood, CSF, and hemeoxygenase-1. We manipulated this system in various ways, incubated it and determined the concentration of vasoactive bilirubin oxidation products that resulted. Conditions where cytochrome oxidase was stimulated caused an increase bilirubin oxidation products (292.6 +/- 39.9 micromol/L respectively, vs. 79.3 +/- 1.3 micromol/L for the basic reaction, p < 0.05), which was attenuated by cyanide. Our data suggest that bilirubin oxidation products may be produced by oxidation(s) requiring an oxygen-utilizing enzyme like cytochrome oxidase.     

A novel intravital method to evaluate cerebral vasospasm in rat models of subarachnoid hemorrhage: a study with synchrotron radiation angiography

Precise in vivo evaluation of cerebral vasospasm caused by subarachnoid hemorrhage has remained a critical but unsolved issue in experimental small animal models. In this study, we used synchrotron radiation angiography to study the vasospasm of anterior circulation arteries in two subarachnoid hemorrhage models in rats. Synchrotron radiation angiography, laser Doppler flowmetry-cerebral blood flow measurement, [(125)I]N-isopropyl-p-iodoamphetamine cerebral blood flow measurement and terminal examinations were applied to evaluate the changes of anterior circulation arteries in two subarachnoid hemorrhage models made by blood injection into cisterna magna and prechiasmatic cistern. Using synchrotron radiation angiography technique, we detected cerebral vasospasm in subarachnoid hemorrhage rats compared to the controls (p<0.05). We also identified two interesting findings: 1) both middle cerebral artery and anterior cerebral artery shrunk the most at day 3 after subarachnoid hemorrhage; 2) the diameter of anterior cerebral artery in the prechiasmatic cistern injection group was smaller than that in the cisterna magna injection group (p<0.05), but not for middle cerebral artery. We concluded that synchrotron radiation angiography provided a novel technique, which could directly evaluate cerebral vasospasm in small animal experimental subarachnoid hemorrhage models. The courses of vasospasm in these two injection models are similar; however, the model produced by prechiasmatic cistern injection is more suitable for study of anterior circulation vasospasm.     

Identification of SNP markers for common CNV regions and association analysis of risk of subarachnoid aneurysmal hemorrhage in Japanese population

Copy number variation (CNV) is emerging as a new tool for understanding human genomic variation, but its relationship with human disease is not yet fully understood. The data for a total of 317,503 genotypes were collected for a genome-wide association study of subarachnoid aneurismal hemorrhage (SAH) in a Japanese population (cases and controls, n = 497) using Illumina HumanHap300 BeadChip^®. To identify multi-allelic CNV markers, we visually inspected all genotype clusters of 317,503 SNP markers covering the whole genome using Illumina’s BeadStudio 3.0^® software. As a result, we identified 597 multi-allelic CNV markers for common (copy loss frequency > 0.05) CNV regions in a Japanese population (n = 497). The identified CNV markers shared the following characteristics: enrichment of Hardy–Weinberg disequilibria, Mendelian inconsistency among families, and high missing genotype rate. All annotated information for those markers is summarized in our database (http://www.snp-genetics.com/user/srch.htm). In addition, we performed case-control association analyses of identified multi-allelic CNV markers with the risk of subarachnoid aneurysmal hemorrhage. One SNP marker (rs1242541) within a CNV region neighboring the Sel-1 suppressor of lin-12-like protein (SEL1L) was significantly associated with a risk of SAH (P = 0.0006). We also validated the CNV around rs1242541 using real-time quantitative polymerase chain reaction (PCR). Information and methods used in this study would be helpful for accurate genotyping of SNPs on CNV regions, which could be used for association analysis of SNP markers within CNV regions.     

Prevention and reversal of vasospasm and ultrastructural changes in basilar artery by continuous infusion of CGS 35066 following subarachnoid hemorrhage

Endothelin-1, a potent vasoconstrictive peptide, has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). The goal of this study was to evaluate the effect of continuous intravenous infusion of a highly selective endothelin-converting enzyme-1 inhibitor, CGS 35066, on the prevention and reversal of cerebral vasospasm following SAH. New Zealand white rabbits were subjected to SAH by injecting autologous arterial blood into the cisterna magna. Infusion of CGS 35066 at dosages of 1, 3, or 10 mg/kg/ day was initiated either 1 hr and 24 hrs later in the prevention and reversal protocols, respectively. Animals were sacrificed by perfusion-fixation 48 hrs after SAH induction. The cross-sectional areas of basilar arteries were measured using computer-assisted videomicroscopy. Ultrastructural changes in basilar arteries were determined using electron microscopy. CGS 35066 significantly prevented and reversed the arterial narrowing after SAH in all three groups. The mean cross-sectional areas of arteries from animals in both the prevention and reversal protocol groups that received 10 mg/kg/day of CGS 35066 did not differ significantly from those of the healthy controls. Histological studies of the basilar artery in the 10 mg/kg/day treatment group did not show pathomorphological changes, such as corrugation of the endothelium seen at 2 days after SAH induction or vacuole formation in the endothelial cells noted in the vehicle-treated SAH group. These findings suggest that CGS 35066 is a promising therapeutic agent for the prevention and reversal of cerebral vasospasm after SAH. It also prevents the pathological changes in vascular walls due to SAH.     

Development of a mathematical model that predicts the outcome of hormone therapy for prostate cancer

We propose a mathematical model that quantitatively reproduces the dynamics of the serum prostate-specific antigen (PSA) level under intermittent androgen suppression (IAS) for prostate cancer. Taking into account the biological knowledge that there are reversible and irreversible changes in a malignant cell, we constructed a piecewise-linear dynamical model where the testosterone dynamics are modelled with rapid shifts between two levels, namely the normal and castrate concentrations of the male hormone. The validity of the model was supported by patient data obtained from a clinical trial of IAS. It accurately reproduced the kinetics of the therapeutic reduction of PSA and predicted the future nadir level correctly. The coexistence of reversible and irreversible changes within the malignant cell provided the best explanation of early progression to androgen independence. Finally, since the model identified patients for whom IAS was effective, it potentially offers a novel approach to individualized therapy requiring the input of time sequence values of PSA only.     

大鼠脑血管痉挛时NO和ET—1变化及尼莫地平的影响

目的探讨蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)时脑组织一氧化氮(NO)和内皮素-1(ET-1)含量变化及尼莫地平(ND)对其影响。方法将135只Wistar大鼠随机均分为SAH组、ND处理组和假手术组,观察手术前后基底动脉管径,及24h内局部脑血流量(rCBF)、脑组织NO和ET-1含量动态改变,并行海马病理检查。结果SAH后rCBF明显而持续降低,基底动脉管径显著缩小;海马CAl区锥体细胞严重受损;脑组织NO和ET-1含量均在SAH后1～24h显著增加(P＜0．05～0．01)。ND处理后使上述异常变化均减轻。结论SAH后脑组织NO、ET-1增多可能参与了CVS所致脑损害过程,ND通过减轻CVS和拮抗脑组织NO及ET-1的病理性改变而发挥脑保护作用。     

Cerebral salt wasting in subarachnoid hemorrhage rats: model, mechanism, and tool

Cerebral salt wasting (CSW) frequently occurs concomitantly with aneurysmal subarachnoid hemorrhage (SAH). CSW induces excessive natriuresis and osmotic diuresis, and reduces total blood volume. As a result, the risk of symptomatic cerebral vasospasm may be elevated. Therefore, it is important to determine the mechanism of CSW. The purpose of this study was to evaluate whether the rat SAH model exhibits CSW and to investigate the relationship between CSW and natriuretic peptides. A SAH model was produced in 24 rats by perforating a cerebral artery with a nylon thread up through the common carotid artery. To evaluate CSW, urine was cumulatively collected from SAH onset to 12 hours and sodium (Na) excretion was analyzed. Body weight and hematocrit were analyzed before and after SAH onset. Concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in plasma were also analyzed. Urine volume and total Na excretion of SAH rats were significantly higher than those of sham rats (p<0.05). Body weight of SAH rats significantly decreased and hematocrit significantly increased (p < 0.05). ANP concentration was significantly decreased in SAH rats (p<0.05). However, BNP concentrations did not change. This study demonstrated for the first time that a rat SAH model exhibited CSW. It was suggested that the cause of CSW was neither ANP nor BNP. In addition, this rat SAH model will be useful for study of CSW after SAH.     

A1/A2 polymorphism of GpIIIa gene and a risk of aneurysmal subarachnoid haemorrhage

Platelet glycoproteins are involved in pathophysiology of cerebrovascular diseases. The aim of this study was to investigate the association between the GpIIIa gene A1/A2 polymorphism and a risk of aneurysmal subarachnoid haemorrhage (SAH) in a Polish population. In a case-control study we genotyped 288 Caucasian patients with aneurysmal SAH and 457 age-, gender- and race-matched controls. The GpIIIa A1/A2 polymorphism was genotyped with RFLP technique. No difference was found in the distribution of the polymorphism between the cases and controls (cases: A1A1—201 (69.8%), A1A2—83 (28.8%) and A2A2—4 (1.4%) vs. controls: A1A1—323 (70.7%); A1A2—128 (28.0%); A2A2—6 (1.3%), P > 0.05. In a multivariate analysis female gender (OR = 1.950; 95%CI: 1.308-2.907), hypertension (OR = 4.774; 95%CI: 3.048-7.478) and smoking (OR = 2.034; 95%CI: 1.366-3.030), but not GpIIIa A1/A2 polymorphism, were independent risk factors for aneurysmal SAH. The GpIIIa A1/A2 polymorphism is not a risk factor of aneurysmal SAH in a Polish population.     

The presence of an extractable substance in the CSF of humans with cerebral vasospasm after subarachnoid haemorrhage that correlates with phosphatase inhibition

The cellular events leading to cerebral vasospasm after subarachnoid haemorrhage are poorly understood, although an increase in smooth muscle myosin light chain phosphorylation has been observed. This study set out to determine if phosphatase inhibition may be involved in the pathological maintenance of tension observed during vasospasm. We found that 1 nM okadaic acid, a type 2A protein phosphatase inhibitor, elicited an increase in rate of O(2) consumption in the porcine carotid artery similar to that by cerebrospinal fluid (CSF) from vasospastic patients (CSF(V), n=5) (control 0.23+/-0.03, CSF(V) 0.84+/-0.16 and okadaic acid 0.85+/-0.02 micromol min(-1) g dwt(-1)). It was also observed that phosphatase inhibition with 1 nM okadaic acid significantly slowed relaxation after a stretch in a similar fashion to CSF(V) haemorrhage. CSF from vasospastic subarachnoid haemorrhage patients, but not from those without vasospasm, contains an extractable substance which modulates myosin light chain phosphorylation in vitro. A phosphatase preparation obtained from the porcine carotid artery dephosphorylated 63+/-2% of the phosphorylated (MLC(20)) substrate in vitro, and non-vasospastic CSF treated enzyme dephosphorylated 60+/-2.6%. Okadaic acid inhibited phosphatase dephosphorylated only 7.5+/-1% of the substrate where CSF(V) treated enzyme dephosphorylated 22+/-2.8% of the substrate. We conclude that inhibition of smooth muscle phosphatase may be involved in the mechanisms associated with cerebral vasospasm after subarachnoid haemorrhage.     

PAX5 gene as a novel methylation marker that predicts both clinical outcome and cisplatin sensitivity in esophageal squamous cell carcinoma

Therapeutic strategies for esophageal cancer largely depend on histopathological assessment. To select appropriate treatments of individual patients, we examined the background molecular characteristics of tumor malignancy and sensitivity to multidisciplinary therapy. Seventy-eight surgically-resected esophageal squamous cell carcinoma (ESCC) cases during 2001–2013 were examined. PAX5, a novel gene methylation marker in ESCC, was evaluated in the specimens, as methylation of this gene was identified as an extremely tumor-specific event in squamous cell carcinogenesis of head and neck. PAX5 methylation status was evaluated by quantitative MSP (QMSP) assays. Mean QMSP value was 15.7 (0–136.3) in ESCCs and 0.3 (0–8.6) in adjacent normal tissues (P < 0.001). The 78 cases were divided into high QMSP value (high QMSP, n = 26) and low QMSP value (low QMSP, n = 52). High QMSP cases were significantly associated with downregulated PAX5 expression (P = 0.040), and showed significantly poor recurrence-free survival [Hazard Ratio (HR) = 2.84; P = 0.005; 95% Confidence Interval (CI): 1.39–5.81] and overall survival (HR = 3.23; P = 0.002; 95%CI: 1.52–7.01) in multivariable analyses with histopathological factors. PAX5-knockdown cells exhibited significantly increased cell proliferation and cisplatin resistance. PAX5 gene methylation can predict poor survival outcomes and cisplatin sensitivity in ESCCs and could be a useful diagnostic tool for cancer therapy selection.     

Corticotropin releasing hormone (CRH) increases beta-endorphin (beta-end like) concentration in cerebrospinal fluid of rats with vasospasm following subarachnoid hemorrhage.

The chronic stage of vasospasm occurring several days after subarachnoid hemorrhage (SAH) is characterized by the development of histopathologic changes in cerebral arteries causing cerebral ischemia. Numerous experimental data indicate the involvement of immune mechanisms in the angiopathy caused by SAH. Endogenous opioids play also an important role in the ischemic lesions of the brain. Corticotropin releasing hormone (CRH) induces the release of beta-endorphin (beta-END) from hypothalamic neurons and also from mononuclear white blood cells. The function of CRH and beta-END in vasospasm following SAH and the interrelationship between neuroendocrine and immune changes requires further elucidation. In the present study we investigated the influence of CRH injected into cerebral cisterna magna (CM) of rats on beta-END-like level in cerebrospinal fluid (CSF) in acute and chronic phase of cerebral vasospasm following artificial SAH. Acutely CRH induced a significant rise of beta-END-like in CSF both in SAH and sham SAH rats. However, in rats subjected to SAH, a single injection of CRH caused a prolonged rise of 5-END in CSF, which was also seen 2 days after SAH, during the chronic phase of vasospasm. The obtained results indicate that CRH increases neuroendocrine changes induced by SAH, probably by an activation of immune cells involved in the patomechanism of chronic vasospasm.     

Effects of interrupted and uninterrupted occlusion of the basilar artery on cerebral blood flow, and on neurological and histological outcome in rats with subarachnoid hemorrhage.

Most neurosurgeons consider temporary vessel occlusion for aneurysmal clipping an effective technique that facilitates dissection between the aneurysm and the parent vessel. It is generally believed that repeated short periods of cerebral ischemia are safer for the brain than a single long episode. The aim of this study was to identify whether interrupted and uninterrupted vessel occlusion differs with regard to changes in brain tissue and cerebral hemodynamics after subarachnoid hemorrhage (SAH). Fifty Spraque Dawley rats (300-350 g) were placed under general anaesthesia and ventilated. The basilar artery was exposed through a transclival approach. Baseline local cerebral blood flow (LCBF) values was measured, and then the basilar artery was punctured, causing subarachnoid hemorrhage (SAH). Group I (n = 24) was subjected to 60 min of interrupted basilar artery occlusion, defined as 5 min of reperfusion after every 10 min of occlusion, group II (n = 26) 60 min of uninterrupted artery occlusion. Three days after completion of the experiment, each rat was neurologically evaluated and decapitated. Coronal brain slices were obtained and stained to assess infarct volume. Immediately after SAH, LCBF fell by 58% in group I, and by 52% in group II. In group I, each ischemic insult brought a similar reduction in LCBF, and after each release of the occlusion there was a rapid rise in flow. In group II, the LCBF values dropped initially and remained at low levels until the end of the study. The 2,3,5 triphenyltetrazolium chloride stained sections showed similar volumes of brainstem infarction in both groups (38.3 +/- 9.2 mm3 vs. 34.3 +/- 8.7 mm3, respectively; p > 0.05). The results suggest that there is no neuroprotective advantage to either interrupted or uninterrupted temporary blockage of blood flow during neurovascular procedures after SAH in the basilar artery region.     

Mate selection in man: Evidence,theory, and outcome

Abstract

This review presents a comprehensive survey of the literature on mate selection and non‐random mating in man. The topics discussed include: (1) genetic aspects of non‐random mating for complex traits; (2) evidence on resemblance between spouses on a large variety of traits such as intelligence, personality, physical characteristics, and sociocultural traits; (3) a critical review of sociological and psychological theories offered to account for assortative mating, and (4) implications of assortative mating for marital satisfaction. It is suggested that the factors leading to choice of marriage partners need to be studied from the point of view of multivariate profiles rather than single traits. Such studies will require sophisticated methodologies of research design and data analysis.     

Plasma metabolomics reveals a potential panel of biomarkers for early diagnosis in acute coronary syndrome

Discovery of new biomarkers is critical for early diagnosis of acute coronary syndrome (ACS). Recent advances in metabolomic technologies have drastically enhanced the possibility of improving the knowledge of its physiopathology through the identification of the altered metabolic pathways. In this study, analyses of peripheral plasma from non-ST segment elevation ACS patients and healthy controls by gas chromatography–mass spectrometry (GC–MC) permitted the identification of 15 metabolites with statistical differences (p < 0.05) between experimental groups. Additionally, validation by GC–MC and liquid chromatography–MC permitted us to identify a potential panel of biomarkers formed by 5-OH-tryptophan, 2-OH-butyric acid and 3-OH-butyric acid. This panel of biomarkers reflects the oxidative stress and the hypoxic state that suffers the myocardial cells and consequently constitutes a metabolomic signature of the atherogenesis process that could be used for early diagnosis of ACS.     

Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay

Background

Currently there are no effective treatments for many neurodegenerative diseases. Reliable biomarkers for identifying and stratifying these diseases will be important in the development of future novel therapies. Lewy Body Dementia (LBD) is considered an under diagnosed form of dementia for which markers are needed to discriminate LBD from other forms of dementia such as Alzheimer’s Disease (AD). This work describes a Label-Free proteomic profiling analysis of cerebral spinal fluid (CSF) from non-neurodegenerative controls and patients with LBD. Using this technology we identified several potential novel markers for LBD. These were then combined with other biomarkers from previously published studies, to create a 10 min multiplexed targeted and translational MRM-LC-MS/MS assay. This test was used to validate our new assay in a larger cohort of samples including controls and the other neurodegenerative conditions of Alzheimer’s and Parkinson’s disease (PD).

Results

Thirty eight proteins showed significantly (p?<?0.05) altered expression in LBD CSF by proteomic profiling. The targeted MRM-LC-MS/MS assay revealed 4 proteins that were specific for the identification of AD from LBD: ectonucleotide pyrophosphatase/phosphodiesterase 2 (p?<?0.0001), lysosome-associated membrane protein 1 (p?<?0.0001), pro-orexin (p?<?0.0017) and transthyretin (p?<?0.0001). Nineteen proteins were elevated significantly in both AD and LBD versus the control group of which 4 proteins are novel (malate dehydrogenase 1, serum amyloid A4, GM_2?activator protein, and prosaposin). Protein-DJ1 was only elevated significantly in the PD group and not in either LBD or AD samples. Correlations with Alzheimer-associated amyloid β-42 levels, determined by ELISA, were observed for transthyretin, GM2 activator protein and IGF2 in the AD disease group (r²?≥?0.39, p?≤?0.012). Cystatin C, ubiquitin and osteopontin showed a strong significant linear relationship (r²?≥?0.4, p?≤?0.03) with phosphorylated–tau levels in all groups, whilst malate dehydrogenase and apolipoprotein E demonstrated a linear relationship with phosphorylated-tau and total-tau levels in only AD and LBD disease groups.

Conclusions

Using proteomics we have identified several potential and novel markers of neurodegeneration and subsequently validated them using a rapid, multiplexed mass spectral test. This targeted proteomic platform can measure common markers of neurodegeneration that correlate with existing diagnostic makers as well as some that have potential to show changes between AD from LBD.

     

Inhibition of brain damage by edaravone, a free radical scavenger, can be monitored by plasma biomarkers that detect oxidative and astrocyte damage in patients with acute cerebral infarction

We assess the availability of plasma biomarkers to monitor the brain damage and the therapeutic efficacy of edaravone. The study consisted of 51 patients with ischemic cerebral infarcts. They were divided into 2 groups: GI (n = 24) had cortical lesions, and GII (n = 27) had lesions in the basal ganglia or brain stem. Edaravone was administered to 27 randomly selected patients (GIa, n = 13; GIIa, n = 14) and its efficacy was studied by comparing their plasma OxLDL, S-100B, and MnSOD levels to those in patients without edaravone (GIb, n = 11, GIIb, n = 13). Three days after the start of edaravone, plasma OxLDL was significantly lower in GIa than GIb patients (0.177 +/- 0.024 ng/microg apoB vs 0.219 +/- 0.026, P < 0.05). In GIIa patients, pre- and posttreatment plasma OxLDL was not significantly different (0.156 +/- 0.013 vs 0.152 +/- 0.020). In GIa patients, S-100B and MnSOD were significantly lower than in GIb patients (P < 0.05). The neurological condition at the time of discharge had recovered in GIa but not GIb patients. Ours is the first evidence to confirm the efficacy of edaravone by plasma biomarkers. In patients with cortical infarcts, edaravone reduced oxidative damage, thereby limiting the degree of brain damage.