Pathological Changes In Brain Research Articles

Synergistic Effect of Serum Homocysteine and Diabetes Mellitus on Brain Alterations.

Both elevated blood homocysteine and diabetes mellitus (DM) are related to cognitive impairments or dementia. A previous study also demonstrated that the association between homocysteine and cognitive decline was much stronger in individuals with DM than in those without DM. This study aimed to examine the interactive effect of blood homocysteine and DM on brain pathological changes including brain atrophy, amyloid-β and tau deposition, and small vessel disease (SVD) related to cognitive impairments. A total of 430 non-demented older adults underwent comprehensive clinical assessment, measurement of serum homocysteine level, [11C] Pittsburgh Compound B (PiB) PET, [18F] AV-1451 PET, and brain MRI. The interactive effect of homocysteine with the presence of DM on brain atrophy, especially in aging-related brain regions, was significant. Higher homocysteine concentration was associated with more prominent brain atrophy in individuals with DM, but not in those without DM. In contrast, interaction effect of homocysteine and DM was found neither on Alzheimer's disease (AD) pathologies, including amyloid-β and tau deposition, nor white matter hyperintensity volume as a measure of SVD. The present findings suggest that high blood homocysteine level and DM synergistically aggravate brain damage independently of AD and cerebrovascular disease. With regard to preventing dementia or cognitive decline in older adults, these results support the importance of strictly controlling blood glucose in individuals with hyperhomocysteinemia and lowering blood homocysteine level in those with DM.

Therapeutic Effect of SPK1 Gene Transfected Adipose Derived Mesenchymal Stem Cells on Experimental Autoimmune Encephalomyelitis Mice and Its Effect on T Helper Cell 17/Regulatory T Cells Balance

Objective To investigate the therapeutic effect of SPK1 gene transfected adipose derived mesenchymal stem cells(ADMSC)on experimental autoimmune encephalomyelitis mice and the effect on T helper cell 17(Th17)/regulatory T(Treg) cells balance. Methods EAE was induced by myelin oligodendrocyte glycoprotein 35-55 in mice.Totally 44 mice were randomly divided into four groups:normal control group(NC group),model group(EAE group),ADMSC group,and ADMSC-SPK1 group.Forty days after injection,the pathological changes of brain and spinal cord,Th17/Treg-related inflammatory markers in brain tissue,expressions of interleukin-17A(IL-17A)and forkhead box protein p3(Foxp3)in brain and spinal cord tissue,and flow cytometric results of spleen immune cells were detected. Results Forty days after the injection,serious inflammatory cell infiltration and demyelination occurred in the brain and spinal cord of EAE group,whereas demyelination and axonal injury were improved in ADMSC group and ADMSC-SPK1 group.Compared with EAE group,the ADMSC group and ADMSC-SPK1 group had significantly improved levels of IL-17A(Z=1.021,P=0.017;Z=1.193, P=0.009)and tumor necrosis factor-α(TNF-α)(Z=2.540,P=0.004; Z=3.005, P=0.006).The expression level of IL-17A in mouse brain and spinal cord tissues was significantly reduced in the ADMSC group(t=10.323,P=0.013;t=7.422,P=0.008),and it was significantly lower in the ADMSC-SPK1 group than in the ADMSC group (t=14.244, P=0.017; t=16.865,P=0.006).The expression level of Foxp3 in the ADMSC group was significantly increased(t=14.544, P=0.008;t=9.420,P=0.002),and it was significantly higher in the ADMSC-SPK1 group than ADMSC group(t=9.654,P=0.005; t=11.535, P=0.009).The proportion of IL-17+IFN-γ+T cells in spleen decreased in ADMSC-SPK1 group,while that of CD25+Foxp3+Treg cells increased. Conclusions ADMSC transfected with SPK1 has an ideal therapeutic effect on EAE mice,and the effect is superior to ADMSC without SPK1 transfection.The mechanism may be that ADMSC-SPK1 can markedly reduce the Th17/Treg cell ratio and decrease the release of related inflammatory cytokines in EAE mice.

High-fat diet induced discrepant peripheral and central nervous systems insulin resistance in APPswe/PS1dE9 and wild-type C57BL/6J mice.

This study was designed to examine whether AD pathological phenotype in APPswe/PS1dE9 (APP/PS1) mice exposed to continuous high-fat diet predispose these murine models to metabolic dysfunction and neuropathological impairments. One-month old male APP/PS1 and C57BL/6J mice were provided with 60% high-fat diet for 6.5 months. After dietary intervention, metabolic phenotyping, cognitive behaviors, AD-related brain pathological changes and insulin signaling were compared. high fat diet induced hyperglycemia, hypercholesterolemia, and aggravated inflammatory stress in both APP/PS1 and C57BL/6J mice. Compared with C57BL/6J control mice, APP/PS1 mice showed lower glucose transporter protein expression in liver, muscle, and brain. High-fat diet caused a decrease of glucose transporter protein expression in muscle and liver but increased cortical glucose transporter protein expression in APP/PS1 mice. High-fat diet-fed APP/PS1 mice demonstrated decreased cognitive function, as well as elevated cortical soluble amyloid-β levels and APP protein expression. Decrease in cortical IR, p-IR protein expression and p-GSK3β/GSK3β ratio were observed in high-fat diet-fed APP/PS1 mice. High-fat diet caused discrepant peripheral and central nervous system metabolic phenotype in APP/PS1 and C57BL/6J mice. AD pathological phenotype might accelerate metabolic changes and cognitive impairment in APP/PS1 mice treated with HFD.

Application of moderate hypothermia while performance of the aortal arch reconstruction in new-born babies in conditions of selective antegrade cerebral perfusion

Objective. To estimate a security of application of moderate hypothermia while performing the aortal arch reconstruction in new-born babies in conditions of selective antegrade cerebral perfusion.
 Materials and methods. In 2010-2019 yrs period in Amosov National Institute of Cardiovascular Surgery and Scientific-Practical Medical Centre of Pediatric Cardiology and Cardio-Surgery in 64 new-born babies the aortal arch reconstruction was performed in conditions of selective antegrade cerebral perfusion in moderate hypothermia. In the investigation only patients with a two-ventricle physiology, in whom further two-ventricular correction was conducted, were included. There were 48 (75%) boys and 16 (25%) girls. Median age of the patients was (1.6 ± 0.8) mo, median body mass - (3.8 ± 1.1) kg, median square of the body surface - (0.24 ± 0.04) m². Echocardiographic investigation and neurosonography were the main diagnostic procedures.
 Results. Hospital mortality have constituted 4.7% (3 patients died). The death cases were not connected with the brain protection procedure. Duration of artificial blood circulation period have had constituted (138.4 ± 58.8) min at average, aortal clamping - (83.1 ± 40 min), selective antegrade cerebral perfusion - (24.4 ± 8.8) min. In 10 (15,6%) patients in early postoperative period the sternum persisted open. In 4 (6.2%) patients in early postoperative period convulsions were noted, which were treated successfully medicinally. Median stay in the Department of Reanimation and Intensive Therapy have constituted (7.1 ± 4.1) days. In late follow-up period the patients were seen from 1 mo till 8.5 yrs. No one patient died. While elective neurosonography conduction the brain pathological changes were absent. The neurological complications symptoms were absent as well.
 Conclusion. Selective antegrade cerebral perfusion with moderate hypothermia constitutes effective and secure method of the brain protection while performance of the aortal arch reconstruction in new-born babies, using median surgical approach in conditions of artificial blood circulation.

The effects of antimony on Alzheimer's disease-like pathological changes in mice brain

We have previously identified antimony (Sb) as a newly nerve poison which leads to neuronal apoptosis. However, the relationship between Sb exposure and Alzheimer's disease (AD) process lacks direct evidence. HE staining and Nissl staining showed significant nerve damage after Sb exposure. Therefore, we further evaluated Sb-associated AD risk by detecting accumulation of β-amyloid protein (Aβ) and neurofibrillary tangles (NFTs) in the brains of mice exposed to Sb for 4 and 8 weeks, and even 1 year. The results showed that dose of 20 mg/kg induced Aβ accumulation, but not tau hyperphosphorylation after exposure for 4 week. Eight weeks later, both 10 and 20 mg/kg dramatically triggered Aβ accumulation and increased tau phosphorylation at ser199. At the same time, 20 mg/kg could also increase tau phosphorylation at ser396 and number of NFTs. One years later, we found all of AD hallmarks detected in present study showed positive results in the brains of mice exposed to Sb at 10 and 20 mg/kg. In summary, our data provided direct evidence of Sb-associated AD risk, drawing more attention to Sb-triggered neurotoxicity.

Traumatic Brain Injury in Children: Sport-related Concussions in Children

ABSTRACT Concussion is a worldwide health concern among children and adolescents. Over the decades concussion has been gradually better recognized as an entity that accounts for a significant disability post head trauma in patients. Patients present with cognitive, somatic and oculo-vestibular symptoms that can be incapacitating. Most concussion symptoms are transient and resolve within 1–2 weeks but can persist for years. Concussion pathophysiology is complex and may not be fully understood but it involves numerous mechanisms including cellular metabolic derangements, cerebral blood inflow, and axonal disruption. With no associated objective biomarkers or visible pathologic brain changes, diagnosis of concussion can be challenging. Many organizations and collaborative groups have suggested numerous definitions and diagnostic criteria for concussion in an attempt to improve the evidence-based clinical assessments and therapies for concussion. Proper assessment and evaluation is crucial starting from counseling of the patient, gradual return to cognitive and physical activity in an individualized treatment plan to ensure a timely return to daily activities and full sport participation. This report provides a grasp over the current state of sport-related concussion knowledge, diagnosis, and clinical evaluation in children and adolescent, with a focus on the ocular symptoms and signs.

Association of Epigenetic Metrics of Biological Age With Cortical Thickness

Magnetic resonance imaging (MRI) studies of aging adults have shown substantial intersubject variability across various brain metrics, and some of this variability is likely attributable to chronological age being an imprecise measure of age-related change. Accurately quantifying one's biological age could allow better quantification of healthy and pathological changes in the aging brain. To investigate the association of DNA methylation (DNAm)-based biological age with cortical thickness and to assess whether biological age acceleration compared with chronological age captures unique variance in cortical thinning. This cross-sectional study used high-resolution structural brain MRI data collected from a sample of healthy aging adults who were participating in a larger ongoing neuroimaging study that began in May 2014. This population-based study accrued participants from the greater Omaha, Nebraska, metropolitan area. One hundred sixty healthy adults were contacted for the MRI component, 82 of whom participated in both DNAm and MRI study components. Data analysis was performed from March to June 2019. Vertexwise cortical thickness, DNAm-based biological age, and biological age acceleration compared with chronological age were measured. A pair of multivariable regression models were computed in which cortical thickness was regressed on DNAm-based biological age, controlling for sex in the first model and also controlling for chronological age in the second model. Seventy-nine adult participants (38 women; mean [SD] age, 43.82 [14.50] years; age range, 22-72 years) were included in all final analyses. Advancing biological age was correlated with cortical thinning across frontal, superior temporal, inferior parietal, and medial occipital regions. In addition, biological age acceleration relative to chronological age was associated with cortical thinning in orbitofrontal, superior and inferior temporal, somatosensory, parahippocampal, and fusiform regions. Specifically, for every 1 year of biological age acceleration, cortical thickness would be expected to decrease by 0.024 mm (95% CI, -0.04 to -0.01 mm) in the left orbitofrontal cortex (partial r, -0.34; P = .002), 0.014 mm (95% CI, -0.02 to -0.01 mm) in the left superior temporal gyrus (partial r, -0.36; P = .001), 0.015 mm (95% CI, -0.02 to -0.01 mm) in the left fusiform gyrus (partial r, -0.38; P = .001), 0.015 mm (95% CI, -0.02 to -0.01 mm) in the right fusiform gyrus (partial r, -0.43; P < .001), 0.019 mm (95% CI, -0.03 to -0.01 mm) in the right inferior temporal sulcus (partial r, -0.34; P = .002), and 0.011 mm (95% CI, -0.02 to -0.01 mm) in the right primary somatosensory cortex (partial r, -0.37; P = .001). To our knowledge, this is the first study to investigate vertexwise cortical thickness in relation to DNAm-based biological age, and the findings suggest that this metric of biological age may yield additional insight on healthy and pathological cortical aging compared with standard measures of chronological age alone.

The MMP-2/TIMP-2 System in Alzheimer Disease.

Alzheimer Disease (AD) is the most prevalent type of dementia. Pathological changes in the AD brain include Amyloid β-protein (Aβ) plaques and Neurofibrillary Tangles (NFTs), as well as extensive neuronal and synaptic loss. Matrix Metalloproteinase-2 (MMP-2) is a neutral, zinc-dependent protease that primarily targets extracellular matrix proteins. MMP-2 activity is strictly controlled, and its dysregulation has been implicated in a variety of pathologies, including AD. In this brief review, we discussed the contributions of dysregulated MMP-2 activity and an imbalanced interaction between MMP-2 and its endogenous inhibitor, Tissue Inhibitors of Metalloproteinase-2 (TIMP-2), to AD. We also described the underlying mechanisms of the effects of MMP-2/TIMP-2, both beneficial and detrimental, on AD, including: (1) MMP-2 directly degrades Aβ resulting in the clearance of Aβ deposits. Conversely, Aβ-induced MMP-2 may contribute to brain parenchymal destruction. (2) MMP-2 induces breakdown of BBB, and this deleterious effect could be reversed by TIMP-2. (3) MMP-2 disrupts oxidative homeostasis in AD. (4) MMP-2 has both proinflammatory/pro-angiogenetic and antiinflammatory/ anti-angiogenetic effects on AD. Besides, we discuss the clinical utility of MMP- 2/TIMP-2 as therapeutic targets for AD.

Progress of RAGE Molecular Imaging in Alzheimer's Disease.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by senile plaques (SPs), which are caused by amyloid beta (Aβ) deposition and neurofibrillary tangles (NFTs) of abnormal hyperphosphorylated tau protein. The receptor for advanced glycation end products (RAGE) binds to advanced glycation end products deposited during vascular dysfunction. Alzheimer’s disease may occur when RAGE binds to Aβ and releases reactive oxygen species, further exacerbating Aβ deposition and eventually leading to SPs and NFTs. As it is involved in early AD, RAGE may be considered as a more potent biomarker than Aβ. Positron emission tomography provides valuable information regarding the underlying pathological processes of AD many years before the appearance of clinical symptoms. Thus, to further reveal the role of RAGE in AD pathology and for early diagnosis of AD, a tracer that targets RAGE is needed. In this review, we first describe the early diagnosis of AD and then summarize the interaction between RAGE and Aβ and Tau that is required to induce AD pathology, and finally focus on RAGE-targeting probes, highlighting the potential of RAGE to be used as an effective target. The development of RAGE probes is expected to aid in AD diagnosis and treatment.

EFFICACY OF AZITHROMYCIN ON EXPERIMENTAL TOXOPLASMOSIS INFECTED MICE

Toxoplasma gondii is an opportunistic protozoan that causes a devastating disease in immunocompromisedindividuals and congenitally infected neonates or children. This study evaluated theefficacy of early Azithromycin treatment of Toxoplasma gondii infected mice with cystogenic Me49 non-virulent strain. Fifty laboratory-bred female Swiss albino mice were divided into 5 groups:G1: Non-Infected, G2: Infected non-treated, G3: Infected and treated by Azithromycin 200mg/kg at 4th day post-infection for 3 days, G4: Infected and treated by Azithromycin 200mg/kg at4th day post-infection for 10 days & G5: Infected and treated by Spiramycin 200mgkg at 4th daypost-infection for 2 weeks, brain cysts’ number, size and histopaholoical changes were assessedafter 3 months. Treatment with Azithromycin for 10 days decreased number and size of braincysts by 70% & 40% respectively without significant difference with Spiramycin treated micethat caused reduction by 74% & 50% respectively. Azithromycin treatment for 3 days caused theleast reduction by 51% & 21% respectively and Azithromycin treatment for 10 days decreasedthe histo-pathological changes in cerebral toxoplasmosis. Azithromycin treatment started at 4thday post-infection was effective than Spiramycin against T. gondii infection with a significant effecton cysts count and size and brain pathological changes. Azithromycin treatment for 10 daysgave better effect than 3 days.

Protective effects of Akkermansia muciniphila on cognitive deficits and amyloid pathology in a mouse model of Alzheimer\u2019s disease

ObjectiveAlzheimer’s disease (AD) is a global health problem without effective methods to alleviate the disease progression. Amyloid β-protein (Aβ) is widely accepted as a key biomarker for AD. Metabolic syndromes, including obesity and insulin resistance, are key high risk factors for AD. Akkermansia muciniphila (Akk), the only representative human gut microbe in the genus Verrucomicrobia, can prevent the weight gain caused by a high-fat diet, repair the damaged integrity of the intestinal epithelium barrier, reduce endotoxin levels in blood and improve insulin resistance. The aim of this study is to explore the impact of Akk administration in AD model mice in different diets.MethodsAPP/PS1 mice were fed either a normal chow diet or a high-fat diet and were treated with Akk by gavage each day for 6 months. The impacts of Akk on glucose metabolism, intestinal barrier and lipid metabolism in the mouse model of AD were determined. Changes in brain pathology and neuroethology were also analyzed.ResultsAkk effectively reduced the fasting blood glucose and serum diamine oxidase levels, and alleviated the reduction of colonic mucus cells in APP/PS1 mice. After treatment with Akk, the APP/PS1 mice showed obviously reduced blood lipid levels, improved hepatic steatosis and scapular brown fat whitening. Moreover, Akk promoted the reduction of Aβ 40–42 levels in the cerebral cortex of APP/PS1 mice, shortened the study time and improved the completion rate in Y-maze tests.ConclusionAkk effectively improved glucose tolerance, intestine barrier dysfunction and dyslipidemia in AD model mice. Our study results suggested that Akk could delay the pathological changes in the brain and relieve impairment of spatial learning and memory in AD model mice, which provides a new strategy for prevention and treatment of AD.

Susceptibility-weighted imaging and transcranial Doppler ultrasound in patients with cerebral small vessel disease.

Cerebral small vessel disease (SVD) is a common accompaniment to aging. Magnetic resonance imaging (MRI) features of SVD include lacunar infarcts (LI) and white matter hyperintensity (WMH). Brain iron deposition is also a known marker of SVD that is associated with cognitive impairment and can be detected with susceptibility-weighted imaging (SWI) MRI technique. According to recent studies, the pulsation of cerebral blood flow can be one of the main factors of the development of pathological brain changes in elderly patients. The objective of this study was to investigate the relationship between the brain iron deposition, cerebral blood flow pulsation, and cognitive impairment in patients with SVD. For the study, 97 patients with diagnosed SVD were selected. The patients were divided into two groups based on the Montreal Cognitive Assessment (MoCA) test scores. All patients underwent MRI in the SWI sequence. Pulsatility index (PI) and resistivity index (RI) were recorded from the middle cerebral artery bilaterally using transcranial Doppler (TCD). The linear regression model showed that the pulsatility index (PI) and resistivity index (RI) were associated with cognitive impairment and brain iron deposition in basal ganglia. The most significant association was found between left globus pallidus severe hypointensity voxels count and left middle cerebral artery (MCA) RI (p = 0.009). The results of the study provide information that TCD indicators may be associated with brain iron deposition and cognitive decline in patients with SVD. Our findings suggest that both brain iron deposition and cerebral hemodynamics abnormalities may play an important role in the pathophysiological mechanisms of SVD.

Effects of Wuweizi syrup on brain aging mice model induced by d-galactose

ObjectiveTo observe the effect of Wuweizi syrup on brain aging mice model induced by d-galactose in mice. Methods72 mice were randomly divided into blank group, model group, naokangling group and low, middle and high dose Wuweizi syrup group. After 3 days of adaptive feeding, except for the blank group, the rest mice were subcutaneously (sc) injected with d-galactose 1.25 g/kg at neck back to replicate the aging model. Sc injection was given for 40 consecutive days, and corresponding drugs were given by gavage on the 11th day of modeling. On the 39th day, the dark experiment was carried out to measure the learning ability of mice. After the last administration for 2 h, brain, liver, thymus and spleen were taken and weighed to calculate the organ index. Blood was taken and CAT, GSH and SOD levels in whole blood were determined. Some brain and liver tissues were taken to prepare homogenates, and MDA levels in tissue homogenates and plasma were measured. Brain, liver, thymus and spleen were stained with HE, and pathological sections were made for observation under light microscope. ResultsCompared with the blank group, in the model group, the incubation period of mice was significantly reduced and the number of shuttle back and forth was significantly increased (P < 0.01); Spleen and brain indexes decreased significantly (P < 0.05), thymus indexes were decreased significantly, and liver indexes were increased significantly (P < 0.01); The levels of CAT, GSH and SOD in whole blood were significantly decreased (P < 0.01); MDA levels in liver homogenates, brain homogenates and plasma were significantly increased (P < 0.01); Pathological changes of brain, liver, thymus and spleen were observed under microscope. Compared with the model group, naokangling group and low, middle and high dose Wuweizi syrup group can significantly improve the incubation period of mice and reduce the number of shuttle back and forth (P < 0.01), can decrease or increase the organ index with different degree (P < 0.01 or P < 0.05), can significantly increase the levels of CAT, GSH and SOD in whole blood (P < 0.01), and significantly reduce the levels of MDA in plasma, liver homogenate and brain homogenate (P < 0.01), as well as can improve pathological changes of brain, liver, thymus and spleen with different degree. ConclusionThe mice aging model was successfully replicated, and Wuweizi syrup can significantly improve the memory, biochemical indexes and pathological status of brain aging model mice.

The role of neuroinflammation on pathogenesis of affective disorders.

Accumulating evidence suggests that neuroinflammation plays an important role in etiology of psychiatric disorders. Neuronflammation involves a combination of psychological, neuroendocrine, and nervous systems resulting in changes of neurotransmitter metabolism, dysregulation of the hypothalamuspituitary-adrenal axis, pathologic microglial cell activation, impaired neuroplasticity, and structural and functional brain changes affecting cognition and emotional behavior. Inflammatory cytokines have been postulated to be the possible link and culprit in the disruption of these systems. The outcome of any type of dysregulation of the immune system in the brain might lead to occurrence of depression, anxiety. This review focuses on the possible impact of dysregulated cytokine networks which may cause pathogenesis of affective disorders such as depression and anxiety.

Positron Emission Tomography After Ischemic Brain Injury: Current Challenges and Future Developments.

Positron emission tomography (PET) is widely used in clinical and animal studies, along with the development of diverse tracers. The biochemical characteristics of PET tracers may help uncover the pathophysiological consequences of cardiac arrest (CA) and ischemic stroke, which include cerebral ischemia and reperfusion, depletion of oxygen and glucose, and neuroinflammation. PubMed was searched for studies of the application of PET for "cardiac arrest," "ischemic stroke," and "targeted temperature management." Available studies were included and classified according to the biochemical properties involved and metabolic processes of PET tracers, and were summarized. The mechanisms of ischemic brain injuries were investigated by PET with various tracers to elucidate the pathological process from the initial decrease of cerebral blood flow (CBF) to the subsequent abnormalities in energy and oxygen metabolism, to the monitoring of inflammation. In general, the trends of cerebral blood flow and oxygen metabolism after ischemic attack are not unidirectional but closely related to the time point of injury and recovery. Glucose metabolism after injury showed significant differences in different brain regions whereas global cerebral metabolic rate of glucose (CMRglc) declined. PET monitoring of neuroinflammation shows comparable efficacy to immunostaining. The technology of PET targeting in brain metabolism and the development of tracers provide new tools to track and evaluate the brain's pathological changes after ischemic brain injury. Despite no existing evidence for an available PET-based prediction method, discoveries of new tracers are expected to provide more possibilities for the whole field.

Ультразвуковая нейровизуализация как технология скрининговой диагностики патологии центральной нервной системы у детей

The article presents the results of analysis of 3466 examinations (2012–2018), obtained from screening of brain (neurosonography) and spinal cord (spinal ultrasonography) in children during an outpatient prophylactic examination (n = 593) and in the infectious hospital as a primary structural diagnostics of patients with a suspected infectious disease (n = 2873). In prophylactic screening, over a half of children (67%) demonstrated pathological changes in brain, of which 4,1% patients had symptomless course of structural deficit, which may cause unfavorable consequences. Spinal ultrasonography during an outpatient screening showed ultrasound symptoms of the spinal cord in 61% cases. When an infectious disease was suspected in the infectious hospital, neurosonography showed pathological changes in brain in 45% patients, and in 90% of cases the revealed disorders were not of infectious nature, but served as the ground for changing the therapeutic tactics, which determined the outcome of the main disease. The presented clinical cases substantiate the need for ultrasound screening of not only the brain but also the spinal cord at dispensarization of young children. The obtained results show the need to perform planned neurosonography at birth, at 1 and 3 months, at 1 year, further on indications stemming from previous examinations. Spinal ultrasonography should be performed to all children at the age of 1 month. The article also presents the experience of sonography screening in children with infectious diseases, which confirms the need to perform neurosonography during primary diagnostics in children of all ages with infectious diseases accompanied by general cerebral syndrome.

Imaging Cerebral Haemorrhage using MRI: Improved Sensitivity of Susceptibility Weighted Imaging (SWI) Compared to Gradient Echo Sequences (GRE)

Background: The appearance of cerebral haemorrhage (CH) as common MR imaging findings raise the question of how MR image acquisition and haemorrhage area quantification can help in understanding brain pathological changes as the result of various disease conditions such as acute brain injury, hypertension amyloid angiopathy and other diverse pathology. Neuroimaging is essential for the clinician to identify the cause of haemorrhage. In this study, we examined 25 cerebral haemorrhage MR images with an objective of comparing two different sequences viz., susceptibility weighted imaging (SWI) and gradient recalled echo (GRE) on same patients and also to quantify the area of haemorrhage using manual selection and gray area threshold (automated selection) in the digital image. Materials and Methods: In this prospective study, MR images were acquired from 25 subjects with acute brain trauma (16) , hypertension (5), and amyloid angiopathy (4), using SWI and GRE MR Sequences, with section thicknesses (3- 5 mm), and magnetic field strengths (1.5T). Individual CH was manually identified and analyzed for haemorrhage area using signal intensity changes by manual and automatic selection of binary threshold hypointense signal by ImageJ software package. Results: By other parameters set as constant, we were able to quantify hypointense signal changes at regions of cerebral haemorrhage on SWI when compared to no such notable changes in GRE in the case of amyloid angiopathy patients. Apart from this, lesions prospectively identified on SWI had a significantly greater area measured on the SWI image than those not prospectively identified on GRE. Conclusions: There is an increased sensitivity in the CH detection in patients with amyloid angiopathy while using SWI sequence when compared to GRE in which we could not identify any signal changes in specific areas. Furthermore, the haemorrhage areas quantified by an automated cropping technique using ImageJ software yielded a precise lesion area method when compared to manual cropping. However, observation on increased sample size in this disease condition is required to confirm these preliminary findings to prognosticate CH.

Advanced diffusion magnetic resonance imaging in patients with Alzheimer's and Parkinson's diseases.

The prevalence of neurodegenerative diseases is increasing as human longevity increases. The objective biomarkers that enable the staging and early diagnosis of neurodegenerative diseases are eagerly anticipated. It has recently become possible to determine pathological changes in the brain without autopsy with the advancement of diffusion magnetic resonance imaging techniques. Diffusion magnetic resonance imaging is a robust tool used to evaluate brain microstructural complexity and integrity, axonal order, density, and myelination via the micron-scale displacement of water molecules diffusing in tissues. Diffusion tensor imaging, a type of diffusion magnetic resonance imaging technique is widely utilized in clinical and research settings; however, it has several limitations. To overcome these limitations, cutting-edge diffusion magnetic resonance imaging techniques, such as diffusional kurtosis imaging, neurite orientation dispersion and density imaging, and free water imaging, have been recently proposed and applied to evaluate the pathology of neurodegenerative diseases. This review focused on the main applications, findings, and future directions of advanced diffusion magnetic resonance imaging techniques in patients with Alzheimer’s and Parkinson’s diseases, the first and second most common neurodegenerative diseases, respectively.

Protective effects of medicinal plant breviscapine on postcerebral hemorrhage in rats.

Medicinal plant breviscapine is shown to exhibit a protective role in tissue damage after cerebral hemorrhage. The effects of breviscapine on neurological deficit score, brain tissue water content, brain pathological tissue changes, blood-brain barrier bidirectional regulation, and inflammatory factors after cerebral hemorrhage in rats were observed. Western blot and real-time quantitative polymerase chain reaction were performed to explore how Periostin and nuclear factor kappa-B pathway-related factors protein expression contribute to the protective effects of breviscapine on brain injury. Breviscapine inhalation could reduce neurological deficit scores and brain tissue water content. Hematoxylin-eosin staining showed that breviscapine could improve the pathological changes of brain tissue and alleviate brain damage. Breviscapine reduced the abnormal increase of Evans blue content caused by a cerebral hemorrhage, and could significantly inhibit the levels of inflammatory factors interleukin-6 and tumor necrosis factor-α. Also, breviscapine significantly inhibited the expressions of Periostin and nuclear factor kappa-B pathway-related factors after cerebral hemorrhage, and alleviate brain damage by down-regulating Periostin expression and inhibiting nuclear factor kappa-β signaling pathway.

Blood biomarkers for memory: toward early detection of risk for Alzheimer disease, pharmacogenomics, and repurposed drugs

Short-term memory dysfunction is a key early feature of Alzheimer’s disease (AD). Psychiatric patients may be at higher risk for memory dysfunction and subsequent AD due to the negative effects of stress and depression on the brain. We carried out longitudinal within-subject studies in male and female psychiatric patients to discover blood gene expression biomarkers that track short term memory as measured by the retention measure in the Hopkins Verbal Learning Test. These biomarkers were subsequently prioritized with a convergent functional genomics approach using previous evidence in the field implicating them in AD. The top candidate biomarkers were then tested in an independent cohort for ability to predict state short-term memory, and trait future positive neuropsychological testing for cognitive impairment. The best overall evidence was for a series of new, as well as some previously known genes, which are now newly shown to have functional evidence in humans as blood biomarkers: RAB7A, NPC2, TGFB1, GAP43, ARSB, PER1, GUSB, and MAPT. Additional top blood biomarkers include GSK3B, PTGS2, APOE, BACE1, PSEN1, and TREM2, well known genes implicated in AD by previous brain and genetic studies, in humans and animal models, which serve as reassuring de facto positive controls for our whole-genome gene expression discovery approach. Biological pathway analyses implicate LXR/RXR activation, neuroinflammation, atherosclerosis signaling, and amyloid processing. Co-directionality of expression data provide new mechanistic insights that are consistent with a compensatory/scarring scenario for brain pathological changes. A majority of top biomarkers also have evidence for involvement in other psychiatric disorders, particularly stress, providing a molecular basis for clinical co-morbidity and for stress as an early precipitant/risk factor. Some of them are modulated by existing drugs, such as antidepressants, lithium and omega-3 fatty acids. Other drug and nutraceutical leads were identified through bioinformatic drug repurposing analyses (such as pioglitazone, levonorgestrel, salsolidine, ginkgolide A, and icariin). Our work contributes to the overall pathophysiological understanding of memory disorders and AD. It also opens new avenues for precision medicine- diagnostics (assement of risk) as well as early treatment (pharmacogenomically informed, personalized, and preventive).