Cerebral White Matter Damage Research Articles

New Concept and Management for Sepsis in Pregnancy and the Puerperium

Abstract Sepsis, which is life-threatening organ dysfunction resulting from a dysregulated host response to infection, remains a major cause for the admission of pregnant women to the intensive care unit and is one of the leading causes of maternal morbidity and mortality. The obstetric causes include uterine infection, septic abortion, and wound infection. The non-obstetric causes include pyelonephritis and pneumonia. Maternal sepsis may also be from obstetrical critical illness, such as obstetric severe hemorrhage, obstetric (amniotic fluid/pulmonary) embolism, acute fatty liver of pregnancy, and congestive heart failure, cardiopulmonary arrest, and major trauma. The most commonly reported pathogens in maternal sepsis include Escherichia coli, Streptococcus, Staphylococcus, and other gram-negative bacteria. Maternal sepsis may cause intrauterine infection, which results in (1) preterm premature rupture of membranes or preterm labor or birth, (2) cerebral white matter damage or cerebral palsy or neurodevelopmental delay, (3) stillbirth, (4) early- or late-onset sepsis, and (5) perinatal death. The “Hour-1 bundle” should be initiated within the first hour of the recognition of sepsis. The use of early, appropriate antibiotics is crucial in the management of maternal sepsis. Fetal status should be monitored. Appropriate and early source control should be provided. The decision for delivery is often quite complex and should be individualized to each patient's clinical scenario while taking into consideration the suspected source of infection, maternal status, fetal well-being, and gestational age. Extracorporeal membrane oxygenation has been increasingly used in refractory sepsis during pregnancy and the puerperium.

Effects of early postnatal sevoflurane exposure on oligodendrocyte maturation and myelination in cerebral white matter of the rat

General anaesthesia may impose significant neurocognitive risks on the developing brain. As brain injury in preterm neonates has a particular predilection for cerebral white matter, we aimed to evaluate the effects of sevoflurane on oligodendrocyte maturation and myelination in a preterm-equivalent rat model. Two-day-old postnatal (P2) Sprague-Dawley rats were exposed to 3.3 % (approximately 1 minimum alveolar concentration [MAC]) or 4.9 % (approximately 1.5 MAC) sevoflurane for 2 h. Physiologic parameters were measured at the end of sevoflurane anaesthesia. Oligodendrocyte proliferation, maturation, and myelination were evaluated by immunofluorescence with specific markers at different time points. Open field test and Morris water maze tests were performed to access behavior changes from P29 to P36. Arterial blood gases values and blood glucose levels were within the normal physiologic range. As compared to control, 4.9 %, but not 3.3 % sevoflurane disturbed oligodendrocyte maturation at P14, resulting in hypomyelination and axonal damage in cerebral white matter at P28. Rats exposed to 4.9 %, but not 3.3 % sevoflurane showed decreased explorative activity and increased anxiety-like behaviour, as well as learning and memory impairments. Furthermore, 4.9 %, but not 3.3 % sevoflurane inhibited oligodendrocyte proliferation in the developing white matter of the rat brain at 12 h post-anaesthesia, with further evidence of widespread reactive astrogliosis. High concentration of sevoflurane (4.9 %) exposure in early postnatal rats may disrupt oligodendrocyte maturation and myelination. Our study has aimed a spotlight on the need for safe and rational use of analgesics in neonates, especially preterm infants.

Genetic and epigenetic factors and early life inflammation as predictors of neurodevelopmental outcomes

Among individuals born very preterm, perinatal inflammation, particularly if sustained or recurring, is highly likely to contribute to adverse neurodevelopmental outcomes, including cerebral white matter damage, cerebral palsy, cognitive impairment, attention-deficit/hyperactivity disorder, and autism spectrum disorder. Antecedents and correlates of perinatal inflammation include socioeconomic disadvantage, maternal obesity, maternal infections, fetal growth restriction, neonatal sepsis, necrotizing enterocolitis, and prolonged mechanical ventilation. Genetic factors can modify susceptibility to perinatal inflammation and to neurodevelopmental disorders. Preliminary evidence supports a role of epigenetic markers as potential mediators of the presumed effects of preterm birth and/or its consequences on neurodevelopment later in life. Further study is needed of factors such as sex, psychosocial stressors, and environmental exposures that could modify the relationship of early life inflammation to later neurodevelopmental impairments. Also needed are pharmacological and non-pharmacological interventions to attenuate inflammation towards the goal of improving the neurodevelopment of individuals born very preterm.

Vascular Cognitive Impairment Caused by Cerebral Small Vessel Disease Is Associated with the TLR4 in the Hippocampus.

Cerebral small vessel disease (CSVD) can lead to leukodystrophy and cognitive impairment. The inflammatory response mediated by Toll-like receptor 4 (TLR4) is involved in the pathological process of CSVD, but the roles of TLR4 in vascular cognitive impairment (VCI) following CSVD are not clear. To explore the roles and mechanisms of TLR4 in the development of VCI. Male spontaneous hypertension rats (SHR) and Wistar Kyoto rats (WKY) were monitored for blood pressure (BP). The spatial learning and memory were assessed every 6 weeks using Morris water maze (MWM). Blood samples from femoral artery were collected and serum was isolated. Cerebral white matter damage was evaluated using a 3.0T magnetic resonance imaging (MRI) every 12 weeks. After 35 weeks, all rats were decapitated, and the expression of TLR4 in the hippocampus was determined using western blot. The number of positive cells of TLR4, active astrocyte and microglia in hippocampus were measured using immunohistochemistry and immunofluorescence. Compared with WKY, the BP of SHR was maintained at a high level. Spatial learning and memory declined. IL-1β and TNF-α levels were elevated. Cranial coronal scanning with T2-weighted MRI showed high signal intensity in corpus callosum and external capsule of SHR. Furthermore, in SHR, the expression of TLR4, GFAP, and Iba1 in the hippocampus were increased. Hypertension can cause small vascular damage and partial white matter degeneration in the brain. SHR showed cognitive impairment with increasing age. High expression of TLR4 and glial cell response in hippocampus is one of the key mechanisms of this disease.

Intrauterine infection affects early growth and neurobehavioral development in neonatal rats

Objective:To explore the effects of intrauterine infection on early growth and neurobehavioral development in neonatal rats. Methods:Escherichia coli (E. coli) was inoculated into uterine cervix of pregnant rats with gestation of 15 d to establish the intrauterine infection model, and the effect on the delivery of pregnant rats was observed. The neonatal rat brain tissue was stained with Hematoxylin-Eosin and the cerebral white matter damage was assessed. Immunohistochemical staining and Western blot analysis were performed to evaluate the expression of glial fibrillary acidic protein (GFAP), 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and neurofilament (NF) in pup brains. Birth weight and early growth development indices were monitored,and neurobehavioral tests were performed to access the change of neurobehavioral development in neonatal rats. Results:The white blood cell count increased significantly in the uterus and placenta of the pregnant rats after intrauterine E. coli infection and no significant impact was observed on the delivery of pregnant rats. Weak staining and focal rarefaction of cerebral white matter from rats at P7 in intrauterine infection group were observed. The expression of GFAP markedly increased (P<0.05) in infection group, while the level of CNPase and NF in pup brains at P7 significantly decreased (P<0.05 or P<0.01). Compared with control group, the neonatal rats in infection group had lower birth weight and slower weight gain during the suckling period (P<0.05 or P<0.01), and the completion times of ear opening, eye opening, surface righting, negative geotaxis, acoustic startle and swimming test in infection group were significantly delayed (P<0.05 or P<0.01). Conclussion:Intrauterine infection in pregnant rats can induce cerebral white matter damage and retardation of early growth and neurobehavioral development in neonatal rats.

Association between Cystatin C and SVD in Chinese population.

Leukoaraiosis is an important clinical feature of cerebral small vessel disease. To date, there is no reliable biomarker to reflect the degree of cerebral small vessel disease and white matter damage. This study aimed to explore the relationship between cystatin C levels and the degree of white matter damage in order to assess whether cystatin C could serve as a biomarker for white matter damage. We conducted a retrospective analysis of 408 non-critically ill hospitalized patients. The included patients underwent related biochemical and cerebral magnetic resonance imaging examinations. The magnetic resonance imaging results were assessed using the Fazekas scale in fluid attenuation inversion recovery imaging. We analyzed the association of each risk factor (sex, age, blood glucose, blood lipid, and cystatin C) with the degree of white matter damage using univariate logistic and multivariate cumulative odds logistic regression (stepwise). Serum cystatin C concentration was closely associated with the degree of white matter damage (odds ratio = 2.14), while age, sex, and hypertension were associated with selective damage of brain white matter. Triglycerides and apolipoprotein A may have a protective effect against white matter damage.

Left ventricular hypertrophy and cognitive function: a systematic review.

Cognitive impairment is common in patients with hypertension. Left ventricular hypertrophy (LVH) is recognised as a marker of hypertension-related organ damage and is a strong predictor of coronary artery disease, heart failure and stroke. There is evidence that LVH is independently associated with cognitive impairment, even after adjustment for the presence of hypertension. We conducted a systematic review that examined cognitive impairment in adults with LVH. Independent searches were performed in Ovid MEDLINE, Ovid psycInfo and PubMed with the terms left ventricular hypertrophy and cognition. Seventy-three studies were identified when both searches were combined. After limiting the search to studies that were: (1) reported in English; (2) conducted in humans; (3) in adults aged 50 years and older; and (4) investigated the relationship between LVH and cognitive performance, nine papers were included in this systematic review. The majority of studies found an association between LVH and cognitive performance. Inspection of results indicated that individuals with LVH exhibited a lower performance in cognitive tests, when compared to individuals without LVH. Memory and executive functions were the cognitive domains that showed a specific vulnerability to the presence of LVH. A possible mechanism for the relationship between LVH and cognition is the presence of cerebral white matter damage. White matter lesions occur frequently in patients with LVH and may contribute to cognitive dysfunction. Together, the results of this review suggest that memory impairment and executive dysfunction are the cognitive domains that showed a particular association with the presence of LVH.

Protective effect of miconazole on rat myelin sheaths following premature infant cerebral white matter injury.

The aim of the present study was to investigate the protective effects of miconazole on myelin sheaths following cerebral white matter damage (WMD) in premature infant rats. Sprague Dawley rats (3-days-old) were randomly divided into four groups (n=30 each) as follows: Sham surgery group, WMD model group, 10 mg/kg/day treatment group and 40 mg/kg/day treatment group. A cerebral white matter lesion model was created by ligating the right common carotid artery for 80 min. Treatment groups were administered with 10 or 40 mg/kg miconazole at 4–8 days following birth (early treatment group) or 5–11 days following birth (late treatment group). Rats in the model group received the same concentration of dimethylsulfoxide. Myelin basic protein (MBP) immunohistochemical staining and western blotting were used to detect the expression of cerebral white matter-specific MBP, and changes in myelin structure were observed using transmission electron microscopy. No swelling or necrosis was observed in the corpus callosum of the sham group rats, whereas rats in the model group demonstrated edema, loose structure, fiber disorder, inflammatory gliocytes and selective white matter lesions. Following treatment with miconazole, MBP expression in the corpus callosum was significantly higher compared with the model group. Furthermore, in the model group, myelin sheaths in the corpus callosum were loose with small vacuoles, there was a marked decrease in thickness and structural damage was observed. Conversely, a marked improvement in myelination was observed in the treatment group. The results of the present study suggest that miconazole is able to promote formation of the myelin sheath to ameliorate premature cerebral white matter lesions caused by ischemia or hypoxia in rats.

Complex spatial and temporally defined myelin and axonal degeneration in Huntington disease.

Although much prior work has focused on the basal ganglia and cortical pathology that defines Huntington's disease (HD), recent studies have also begun to characterize cerebral white matter damage (Rosas et al., 2006; Dumas et al., 2012; Poudel et al., 2014). In this study, we investigated differences in the large fascicular bundles of the cerebral white matter of gene-positive HD carriers, including pre-manifest individuals and early symptomatic patients, using recently developed diffusion tractography procedures. We examined eighteen major fiber bundles in 37 patients with early HD (average age 55.2 ± 11.5, 14 male, 23 female), 31 gene-positive, motor negative pre-symptomatic HD (PHD) (average age 48.1 ± 11.5, 13 male, 18 female), and 38 healthy age-matched controls (average age 55.7 ± 8.6, 14 male, 24 female), using the TRActs Constrained by UnderLying Anatomy (TRACULA) procedure available as part of the FreeSurfer image processing software package. We calculated the mean fractional anisotropy (FA) and the mean radial (RD) and axial diffusivities (AD) for each fiber bundle. We also evaluated the relationships between diffusion measures, cognition and regional cortical thinning. We found that early changes in RD of select tracts in PHD subjects were associated with impaired performance on neuropsychological tests, suggesting that early changes in myelin might underlie early cognitive dysfunction. Finally, we found that increases in AD of select tracts were associated with regionally select cortical thinning of areas known to atrophy in HD, including the sensorimotor, supramarginal and fusiform gyrus, suggesting that AD may be reflecting pyramidal cell degeneration in HD. Together, these results suggest that white matter microstructural changes in HD reflect a complex, clinically relevant and dynamic process.

Sensory modulation in preterm children: Theoretical perspective and systematic review.

BackgroundNeurodevelopmental sequelae in preterm born children are generally considered to result from cerebral white matter damage and noxious effects of environmental factors in the neonatal intensive care unit (NICU). Cerebral white matter damage is associated with sensory processing problems in terms of registration, integration and modulation. However, research into sensory processing problems and, in particular, sensory modulation problems, is scarce in preterm children.AimThis review aims to integrate available evidence on sensory modulation problems in preterm infants and children (<37 weeks of gestation) and their association with neurocognitive and behavioral problems.MethodRelevant studies were extracted from PubMed, EMBASE.com and PsycINFO following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria included assessment of sensory modulation in preterm born children (<37 weeks of gestation) or with prematurity as a risk factor.ResultsEighteen studies were included. Results of this review support the presence of sensory modulation problems in preterm children. Although prematurity may distort various aspects of sensory modulation, the nature and severity of sensory modulation problems differ widely between studies.ConclusionsSensory modulation problems may play a key role in understanding neurocognitive and behavioral sequelae in preterm children. Some support is found for a dose-response relationship between both white matter brain injury and length of NICU stay and sensory modulation problems.

Abstract TMP53: Preeclampsia Leads to Long Term Cerebral White Matter Damage and Cortical Atrophy: a Magnetic Resonance Imaging Study

Introduction: Women with a history of preeclampsia have a two-fold higher risk of acute ischemic stroke even after controlling for classic cardiovascular risk factors. We determined whether specific patterns in cerebral damage are present after preeclampsia that may explain this risk. Methods: We performed brain magnetic resonance imaging in women between 5 and 15 years after either a preeclamptic or normotensive pregnancy. Analysis of white matter structure was undertaken using voxel-based segmentation of fluid attenuation inversion recovery sequences to assess white matter lesion volume and diffusion tensor imaging to measure microstructural integrity. Voxel-based analysis of grey matter volumes was performed in T1 weighted sequences with adjustment for skull size. Cardiovascular, obstetric profiles were assessed. Results: Thirty-four previously preeclamptic women (aged 42.8 ± 5.1 years, mean ± SD) and 49 controls were included. Previously preeclamptic women had reduced cortical grey matter volume (523.2 ± 30.1 vs 544.4 ± 44.7 ml, p&lt;0.05) and, although both groups displayed frontal white matter damage, changes were more extensive in previously preeclamptic women. They displayed increased temporal lobe white matter disease (lesion volume: 23.2 ± 24.9 vs 10.9 ± 15.0 ml, p&lt;0.05) and altered microstructural integrity (radial diffusivity 538 ± 19 vs. 526 ± 18*10 -6 mm 2 /sec, p&lt;0.01), which also extended to occipital and parietal lobes. The degree of temporal lobe white matter change in previously preeclamptic women was independent of their current cardiovascular risk profile (p&lt;0.05) and increased with time from index pregnancy (Figure). Conclusions: A history of preeclampsia is associated with temporal lobe white matter damage and cortical atrophy in young women, which is out of proportion to their classic cardiovascular risk profile and increases with time from pregnancy, consistent with ongoing susceptibility and cumulative brain damage.

Activated ClC-2 Inhibits p-Akt to Repress Myelination in GDM Newborn Rats

This study aims to investigate the effect and mechanism of type 2 voltage-gated chloride channel (ClC-2) on myelin development of newborn rats' cerebral white matter with gestational diabetes mellitus (GDM). In this study, GDM model was induced in late pregnant rat model. The alteration of ClC-2 expression in various developmental stages of cerebral white matter with/without being exposed to high glucose was analyzed using RT-PCR, active oxygen detection, TUNEL staining, Western Blot as well as immuno-histochemical staining. Our results showed that ClC-2 mRNA and protein expressions in GDM group were significantly increased in white matter of fetal rats after E18 stage, and elevated the level of TNF-α and iNOS in white matter at P0 and P3 stage of newborn rats. Meanwhile, In GDM group, reactive oxygen species (ROS) levels of the white matter at E18, P0, and P3 stage were significantly higher than control group. Furthermore, the expression level of myelin transcription factor Olig2 at P0 stage and CNPase at P3 stage were strikingly lower than that of the control group. In GDM group, ClC-2 expression in the corpus callosum (CC) and cingulate gyrus (CG) regains, and TUNEL positive cell number were increased at P0 and P3 stage. However, PDGFα positive cell number at P0 stage and CNPase expression at P3 stage were significantly decreased. Caspase-3 was also increased in those white matter regions in GDM group, but p-Akt expression was inhibited. While DIDS (a chloride channel blocker) can reverse these changes. In conclusion, ClC-2 and caspase-3 were induced by GDM, which resulted in apoptosis and myelination inhibition. The effect was caused by repressing PI3K-Akt signaling pathway. Application of ClC-2 inhibitor DIDS showed protective effects on cerebral white matter damage stimulated by high glucose concentration.

Relation between brain temperature and white matter damage in subacute carbon monoxide poisoning.

In the previous studies, carbon monoxide (CO) poisoning showed an imbalance between cerebral perfusion and metabolism in the acute phase and the brain temperature (BT) in these patients remained abnormally high from the acute to the subacute phase. As observed in chronic ischemic patients, BT can continuously remain high depending on impairments of cerebral blood flow and metabolism; this is because heat removal and production system in the brain may mainly be maintained by the balance of these two factors; thus, cerebral white matter damage (WMD) affecting normal metabolism may affect the BT in patients with CO poisoning. Here, we investigated whether the BT correlates with the degree of WMD in patients with subacute CO-poisoning. In 16 patients with subacute CO-poisoning, the BT and degree of WMD were quantitatively measured by using magnetic resonance spectroscopy and the fractional anisotropy (FA) value from diffusion tensor imaging dataset. Consequently, the BT significantly correlated with the degree of WMD. In particular, BT observed in patients with delayed neuropsychiatric sequelae, a crucial symptom with sudden-onset in the chronic phase after CO exposure, might indicate cerebral hypo-metabolism and abnormal hemodynamics like “matched perfusion,” in which the reduced perfusion matches the reduced metabolism.

Hyper-coherence and increased energy of gamma oscillations in patient with first onset schizophrenia and cerebral white matter damage

Abstract Background: According to current knowledge, gamma frequency is closely related to the functioning of neural networks underlying the basic activity of the brain and mind. Disorders in mechanisms synchronizing brain activity observed in patients diagnosed with schizophrenia are at the roots of neurocognitive disorders and psychopathological symptoms of the disease. Synchronization mechanisms are also related to the structure and functional effectiveness of the white matter. So far, not many analysis has been conducted concerning changes in the image of high frequency in patients with comorbid schizophrenia and white matter damage. The aim of this research was to present specific features of gamma waves in subjects with different psychiatric diagnoses and condition of brain structure. Methods: Quantitative analysis of an EEG record registered from a patient diagnosed with schizophrenia and comorbid white matter hyperintensities (SCH+WM), a patient with an identical diagnosis but without structural brain changes present in the MRI (SCH-WM) of a healthy control (HC). The range of gamma waves has been obtained by using analogue filters. In order to obtain precise analysis, gamma frequencies have been divided into three bands: 30-50Hz, 50-70Hz, 70-100Hz. Matching Pursuit algorithm has been used for signal analysis enabling assessing the changes in signal energy. Synchronization effectiveness of particular areas of the brain was measured with the aid of coherence value for selected pairs of electrodes. Results: The electrophysiological signals recorded for the SCH+WM patient showed the highest signal energy level identified for all the analyzed bands compared to the results obtained for the same pairs of electrodes of the other subjects. Coherence results revealed hipercompensation for the SCH+WM patient and her level differed substantially compared to the results of the other subjects. Conclusions: The coexistence of schizophrenia with white matter damage can significantly disturb parameters of neural activity with high frequencies. The paper discusses possible explanations for the obtained results.

Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers.

Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic traumatic encephalopathy, which is characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths of cortical sulci. We developed an mTBI paradigm to explore effects of repetitive concussive-type injury over several months in mice with a human tau genetic background (hTau). Two injuries were induced in the hTau mice weekly over a period of 3 or 4 months and the effects were compared with those in noninjured sham animals. Behavioral and in vivo measures and detailed neuropathological assessments were conducted 6 months after the first injury. Our data confirm impairment in cerebral blood flow and white matter damage. This was accompanied by a 2-fold increase in total tau levels and mild increases in tau oligomers/conformers and pTau (Thr231) species in brain gray matter. There was no evidence of neurofibrillary/astroglial tangles, neuropil threads, or perivascular foci of tau immunoreactivity. There were neurobehavioral deficits (ie, disinhibition and impaired cognitive performance) in the mTBI animals. These data support the relevance of this new mTBI injury model for studying the consequences of chronic repetitive mTBI in humans, and the role of tau in TBI.

The significance of periventricular leukomalacia on ophthalmic outcome

Aim: Periventricular leukomalacia (PVL) is a type of cerebral white matter damage commonly arising within neonates born prematurely. This review aims to evaluate the literature relating to the long-term ophthalmic outcomes following PVL, focussing on the relationship between neuro-imaging and visual out- come. Methods: A literature review was undertaken between October 2013 and January 2015. Articles were sourced using PubMed, ResearchGate and forward citation searches. Results: PVL is shown to increase an individual’s chance of developing ocular defects, namely cerebral visual impairment, strabismus, visual field defects and visuoperceptual anomalies. The severity and extent of PVL is directly proportional to both the chance of developing an ocular defect, and the severity of said ocular defect; however, there is not a perfect correlation and ophthalmic outcome is specific to each individual. There have also been reports of strabismus being the presenting factor, leading to an investigation which revealed the presence of PVL that had been missed during the neonatal period. Neuro-imaging has been shown to have some predictive ability, varying depending on the area of the visual pathway examined, and the aspect of visual outcome predicted. Conclusions: While predictive results gathered via neuro-imaging can offer insight into visual outcome, these must be consolidated through non-radiological clinical testing. Strabismus has been documented as a presenting factor in patients with PVL. Therefore the initial presentation of a patient with PVL, where the diagnosis has been missed during the neonatal period, may be through the orthoptic department.

MRI findings and analysis of risk factors for brain injury in premature infants with bronchopulmonary dysplasia

Objective To investigate the correlation between brain injury and premature infants with bronchopulmonary dysplasia (BPD) and to analyze the risk factors of brain injury in premature infants with BPD based on MRI changes. Methods A total of 113 premature infants diagnosed with BPD were studied as case group from January 2010 to December 2014 at the neonatal ward of Shengjing Hospital of China Medical University.One hundred and sixty-two premature infants without BPD were selected as control group.There were no significant differences in gestational age and birth weight between the two groups.All cases were performed MRI examination in hospital.The occurrence of brain injuries(white matter injury and intracranial hemorrhage) were compared based on MRI changes between the two groups, and the risk factors of brain injury in case group were analyzed. Results The case group and control group were performed MRI on (33.73±16.00) d, (24.40±12.29) d after birth respectively.The ratio of brain injury, intracranial hemorrhage, cerebral white matter damage and severe brain injury of case group was higher than those of the control group(48.7% vs. 32.7%, 31.9% vs. 21.6%, 31.9% vs. 21.6%, 16.8% vs. 8.6%, respectively). The differences were significant in the ratio of brain injury and severe brain injury (P=0.008, P=0.040, respectively). Logistic regression analysis showed that postnatal infection was a risk factor for brain injury of the case group(OR=2.21, 95%CI 1.04~4.72, P<0.05). Conclusion More brain injury(including the white matter injury and intracranial hemorrhage) and severe brain injury(including grade III~IV intraventricular hemorrhage and periventricular leukomalacia) are detected in premature infants with BPD.Postnatal infection is a risk factor of brain injury for premature infants with BPD. Key words: Premature infants; Bronchopulmonary dysplasia; Brain injury; Magnetic resonance imaging

Is Vasomotion in Cerebral Arteries Impaired in Alzheimer's Disease?

A substantial body of evidence supports the hypothesis of a vascular component in the pathogenesis of Alzheimer’s disease (AD). Cerebral hypoperfusion and blood-brain barrier dysfunction have been indicated as key elements of this pathway. Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder, frequent in AD, characterized by the accumulation of amyloid-β (Aβ) peptide in cerebral blood vessel walls. CAA is associated with loss of vascular integrity, resulting in impaired regulation of cerebral circulation, and increased susceptibility to cerebral ischemia, microhemorrhages, and white matter damage. Vasomotion— the spontaneous rhythmic modulation of arterial diameter, typically observed in arteries/arterioles in various vascular beds including the brain— is thought to participate in tissue perfusion and oxygen delivery regulation. Vasomotion is impaired in adverse conditions such as hypoperfusion and hypoxia. The perivascular and glymphatic pathways of Aβ clearance are thought to be driven by the systolic pulse. Vasomotion produces diameter changes of comparable amplitude, however at lower rates, and could contribute to these mechanisms of Aβ clearance. In spite of potential clinical interest, studies addressing cerebral vasomotion in the context of AD/CAA are limited. This study reviews the current literature on vasomotion, and hypothesizes potential paths implicating impaired cerebral vasomotion in AD/CAA. Aβ and oxidative stress cause vascular tone dysregulation through direct effects on vascular cells, and indirect effects mediated by impaired neurovascular coupling. Vascular tone dysregulation is further aggravated by cholinergic deficit and results in depressed cerebrovascular reactivity and (possibly) impaired vasomotion, aggravating regional hypoperfusion and promoting further Aβ and oxidative stress accumulation.

Fructus mume alleviates chronic cerebral hypoperfusion-induced white matter and hippocampal damage via inhibition of inflammation and downregulation of TLR4 and p38 MAPK signaling.

BackgroundFructus mume (F. mume) has been used as a traditional medicine for many years in Asian countries. The present study was designed to determine the effect of a 70% ethanol extract of F. mume on white matter and hippocampal damage induced by chronic cerebral hypoperfusion.MethodsPermanent bilateral common carotid artery occlusion (BCCAo) was performed on male Wistar rats to induce chronic cerebral hypoperfusion. Daily oral administration of F. mume (200 mg/kg) was initiated 21 days after BCCAo and continued for 42 days. The experimental groups in this study were divided into three groups: a sham-operated group, a BCCAo group, and a BCCAo group that was administered with the F. mume extract. The activation of glial cells, including microglia and astrocytes, and the levels of myelin basic protein (MBP), inflammatory mediators, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and p38 mitogen-activated protein kinase (MAPK) phosphorylation were measured in brains from rats subjected to chronic BCCAo.ResultsOur results revealed that F. mume alleviates the reduction in MBP expression caused by chronic BCCAo in the white matter and the hippocampus and significantly attenuates microglial and astrocytic activation induced by chronic BCCAo in the optic tract of white matter. In addition, F. mume treatment reduced the increased expression of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β) and interleukin-6 (IL-6), as well as the activation of TLR4/MyD88 and p38 MAPK signaling, in the hippocampus of rats subjected to chronic BCCAo.ConclusionTaken together, our findings demonstrate that brain injury induced by chronic BCCAo is ameliorated by the anti-inflammatory effects of F. mume via inhibition of MBP degradation, microglial and astrocytic activation, increased inflammatory mediator expression, and activated intracellular signalings, including TLR4 and p38 MAPK, implying that F. mume is potentially an effective therapeutics for the treatment of vascular dementia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-015-0652-1) contains supplementary material, which is available to authorized users.

Abstract 221: Regional Vulnerability within White Matter tracts to White Matter Hyperintensities: a Diffusion Tensor Imaging Tractography Study

Background: Characterizing the impact of cerebral white matter (WM) damage on age related cognitive decline is of growing interest. White matter hyperintensities (WMH) and reduced microstructural WM integrity, as expressed by diffusion tensor imaging (DTI), have been associated with increased risk of clinically cognitive decline in the elderly, but the regional vulnerability within certain WM tracts to WMH is not well understood. Characterizing the implication and interactions of microstructural integrity and WMH within specific WM tracts would further elucidate mechanisms of cognitive decline in normal aging. Methods: 410 cognitively normal individuals from the Offspring Framingham Heart Study, aged 72.5±7.5 ([54.2; 104.9]), received a comprehensive clinical evaluation and brain MRI including FLAIR and DTI sequences. WM tractography was performed from DTI using FSL tools, resulting in 27 fiber tracts maps for each subject. WMHs were detected on FLAIR scans using a standardized protocol and coregistered to the subject DTI space. The mean fractional anisotrophy (mFA) within each tract was computed. Superimposition of WMH masks onto fiber tracts maps was used to calculate the overlap ratio of WMH (WMHor) within each tract. For each tract, mFA was regressed against the age and tract size and resulting residuals related to WMHor using a linear regression model. Results: The highest rates of WMHor were found within the thalamic radiations (range: [0- 28%]) and the inferior longitudinal fasciculi ([0- 29%]). Lower mFA was independently associated with larger WMHor within almost all association and projection fibers (p values&lt;0.05). Correcting for the overall WMH burden did not significantly alter the results. Discussion: Regional mean FA has been previously associated with the overall WMH burden. We extended this finding by showing that, independently of the overall WM injury, microstructural WM integrity was associated with WMH within specific fiber tracts. Further investigations are needed to detangle the impact of specific tract disruption from that of more generalized subtle WM injury on cognitive decline.