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https://www.readbyqxmd.com/read/28404943/melatonin-protects-against-blood-brain-barrier-damage-by-inhibiting-the-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway-after-lps-treatment-in-neonatal-rats
#1
Yingying Hu, Zhouguang Wang, Shulin Pan, Hongyu Zhang, Mingchu Fang, Huai Jiang, Hao Zhang, Zhengzheng Gao, Kebin Xu, Zhenmao Li, Jian Xiao, Zhenlang Lin
Hypoxic-ischemic and inflammatory (HII) induces the disruption of blood-brain barrier (BBB) which leads to inflammatory responses and neuronal cell death, resulting in brain secondary damage. Previous studies showed that melatonin produced potent neuroprotective effects in neonatal hypoxic-ischaemic models. However, the relationship between BBB disruption and melatonin in HII was still unclear. The present study therefore investigated the beneficial effects of melatonin on BBB after HII and the underlying mechanisms...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28391258/dexmedetomidine-combined-with-therapeutic-hypothermia-is-associated-with-cardiovascular-instability-and-neurotoxicity-in-a-piglet-model-of-perinatal-asphyxia
#2
Mojgan Ezzati, Go Kawano, Eridan Rocha-Ferreira, Daniel Alonso-Alconada, Jane K Hassell, Kevin D Broad, Igor Fierens, Bobbi Fleiss, Alan Bainbridge, David L Price, Pardis Kaynezhad, Brian Anderson, Mariya Hristova, Ilias Tachtsidis, Xavier Golay, Pierre Gressens, Robert D Sanders, Nicola J Robertson
The selective α2-adrenoreceptor agonist dexmedetomidine has shown neuroprotective, analgesic, anti-inflammatory, and sympatholytic properties that may be beneficial in neonatal encephalopathy (NE). As therapeutic hypothermia is only partially effective, adjunct therapies are needed to optimize outcomes. The aim was to assess whether hypothermia + dexmedetomidine treatment augments neuroprotection compared to routine treatment (hypothermia + fentanyl sedation) in a piglet model of NE using magnetic resonance spectroscopy (MRS) biomarkers, which predict outcomes in babies with NE, and immunohistochemistry...
April 8, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28265034/extracellular-matrix-inflammation-in-vascular-cognitive-impairment-and-dementia
#3
REVIEW
Gary A Rosenberg
Vascular cognitive impairment and dementia (VCID) include a wide spectrum of chronic manifestations of vascular disease related to large vessel strokes and small vessel disease (SVD). Lacunar strokes and white matter (WM) injury are consequences of SVD. The main vascular risk factor for SVD is brain hypoperfusion from cerebral blood vessel narrowing due to chronic hypertension. The hypoperfusion leads to activation and degeneration of astrocytes with the resulting fibrosis of the extracellular matrix (ECM)...
March 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28118831/translational-models-for-vascular-cognitive-impairment-a-review-including-larger-species
#4
REVIEW
Atticus H Hainsworth, Stuart M Allan, Johannes Boltze, Catriona Cunningham, Chad Farris, Elizabeth Head, Masafumi Ihara, Jeremy D Isaacs, Raj N Kalaria, Saskia A M J Lesnik Oberstein, Mark B Moss, Björn Nitzsche, Gary A Rosenberg, Julie W Rutten, Melita Salkovic-Petrisic, Aron M Troen
BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015)...
January 25, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28011042/glial-changes-and-evidence-for-apoptosis-in-the-brain-of-cats-infected-by-cytauxzoon-felis
#5
L L Clarke, P M Krimer, D R Rissi
Ischaemic neuropathological changes associated with Cytauxzoon felis infection in cats have been reported recently. This paper describes the associated glial changes and the evidence for apoptosis in the brain of cats infected naturally by C. felis. Sections of brain from eight affected cats and eight age- and sex-matched control cats were evaluated by immunohistochemistry for expression of glial fibrillary acidic protein, CD18 and cleaved caspase-3. Vascular changes in the leptomeninges and parenchyma, the number of positive astrocytes and phagocytic cells (microglia or macrophages) and the average astrocytic cytoplasmic area and number and length of astrocytic processes were quantified, and a mean value for the grey and white matter in both groups was generated...
December 20, 2016: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/27318323/the-active-metabolite-of-prasugrel-r-138727-improves-cerebral-blood-flow-and-reduces-cerebral-infarction-and-neurologic-deficits-in-a-non-human-primate-model-of-acute-ischaemic-stroke
#6
Atsuhiro Sugidachi, Makoto Mizuno, Kousaku Ohno, Joseph A Jakubowski, Atsuyuki Tomizawa
Previously, we showed preventive effects of prasugrel, a P2Y12 antagonist, in a non-human primate model of thrombotic middle cerebral artery occlusion (MCAO); however, it remains unclear if P2Y12 inhibition after MCAO reduces cerebral injury and dysfunction. Here we investigated the effects of R-138727, the major active metabolite of prasugrel, on ex vivo platelet aggregation at 5min, 15min, 60min, and 24h after administration to non-human primates (n=3). A single intravenous dose of R-138727 (0.03-0.3mg/kg) resulted in significant and sustained dose-related effects on platelets for up to 24h...
October 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27047695/plasticity-in-the-neonatal-brain-following-hypoxic-ischaemic-injury
#7
REVIEW
Eridan Rocha-Ferreira, Mariya Hristova
Hypoxic-ischaemic damage to the developing brain is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The developmental stage of the brain and the severity of the insult influence the selective regional vulnerability and the subsequent clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI) of periventricular white matter in preterm infants predisposes the immature brain to motor, cognitive, and sensory deficits, with cognitive impairment associated with earlier gestational age...
2016: Neural Plasticity
https://www.readbyqxmd.com/read/26760212/proton-gated-ca-2-permeable-trp-channels-damage-myelin-in-conditions-mimicking-ischaemia
#8
Nicola B Hamilton, Karolina Kolodziejczyk, Eleni Kougioumtzidou, David Attwell
The myelin sheaths wrapped around axons by oligodendrocytes are crucial for brain function. In ischaemia myelin is damaged in a Ca(2+)-dependent manner, abolishing action potential propagation. This has been attributed to glutamate release activating Ca(2+)-permeable N-methyl-D-aspartate (NMDA) receptors. Surprisingly, we now show that NMDA does not raise the intracellular Ca(2+) concentration ([Ca(2+)]i) in mature oligodendrocytes and that, although ischaemia evokes a glutamate-triggered membrane current, this is generated by a rise of extracellular [K(+)] and decrease of membrane K(+) conductance...
January 28, 2016: Nature
https://www.readbyqxmd.com/read/25823427/does-caspase-6-have-a-role-in-perinatal-brain-injury
#9
Ana A Baburamani, Yasuka Miyakuni, Regina Vontell, Veena G Supramaniam, Pernilla Svedin, Mary Rutherford, Pierre Gressens, Carina Mallard, Satoru Takeda, Claire Thornton, Henrik Hagberg
Apoptotic mechanisms are centre stage for the development of injury in the immature brain, and caspases have been shown to play a pivotal role during brain development and in response to injury. The inhibition of caspases using broad-spectrum agents such as Q-VD-OPh is neuroprotective in the immature brain. Caspase-6, an effector caspase, has been widely researched in neurodevelopmental disorders and found to be important following adult stroke, but its function in the neonatal brain has yet to be detailed...
2015: Developmental Neuroscience
https://www.readbyqxmd.com/read/25001084/brain-involvement-in-patients-with-inflammatory-bowel-disease-a-voxel-based-morphometry-and-diffusion-tensor-imaging-study
#10
Anastasia K Zikou, Maria Kosmidou, Loukas G Astrakas, Loukia C Tzarouchi, Epameinondas Tsianos, Maria I Argyropoulou
OBJECTIVES: To investigate structural brain changes in inflammatory bowel disease (IBD). METHODS: Brain magnetic resonance imaging (MRI) was performed on 18 IBD patients (aged 45.16 ± 14.71 years) and 20 aged-matched control subjects. The imaging protocol consisted of a sagittal-FLAIR, a T1-weighted high-resolution three-dimensional spoiled gradient-echo sequence, and a multisession spin-echo echo-planar diffusion-weighted sequence. Differences between patients and controls in brain volume and diffusion indices were evaluated using the voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) methods, respectively...
October 2014: European Radiology
https://www.readbyqxmd.com/read/24628787/cx3cr1-rnai-inhibits-hypoxia-induced-microglia-activation-via-p38mapk-pkc-pathway
#11
Yong Liu, Tianzhi Zhao, Zhao Yang, Qianning Li
There is accumulating evidence which demonstrates that chronic cerebral ischaemia can induce white matter lesions (WMLs), and microglia-activation-mediated cytokines and proteases releasing during the ischaemia might play a vital role in pathogenesis. In addition, hypoxia-induced upregulated expression of fractalkine promotes the activation of microglia and their migration to the lesions through interaction with its receptor CX3CR1. However, the specific mechanisms involved in fractalkine/CX3CR1-mediated microglial activation have not been fully identified...
April 2014: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/24618270/pathophysiology-of-white-matter-perfusion-in-alzheimer-s-disease-and-vascular-dementia
#12
Rachel Barker, Emma L Ashby, Dannielle Wellington, Vivienne M Barrow, Jennifer C Palmer, Patrick G Kehoe, Margaret M Esiri, Seth Love
Little is known about the contributors and physiological responses to white matter hypoperfusion in the human brain. We previously showed the ratio of myelin-associated glycoprotein to proteolipid protein 1 in post-mortem human brain tissue correlates with the degree of ante-mortem ischaemia. In age-matched post-mortem cohorts of Alzheimer's disease (n = 49), vascular dementia (n = 17) and control brains (n = 33) from the South West Dementia Brain Bank (Bristol), we have now examined the relationship between the ratio of myelin-associated glycoprotein to proteolipid protein 1 and several other proteins involved in regulating white matter vascularity and blood flow...
May 2014: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/24058380/advances-in-our-understanding-of-the-pathophysiology-detection-and-management-of-cerebral-amyloid-angiopathy
#13
Octavio M Pontes-Neto, Eitan Auriel, Steven M Greenberg
Cerebral amyloid angiopathy (CAA) is pathologically defined as the deposition of amyloid protein, most commonly the amyloid β peptide (Aβ), primarily within the media and adventitia of small and medium-sized arteries of the leptomeninges, cerebral and cerebellar cortex. This deposition likely reflects an imbalance between Aβ production and clearance within the brain and leads to weakening of the overall structure of brain small vessels, predisposing patients tolobar intracerebral haemorrhage (ICH), brain ischaemia and cognitive decline...
2012: European Neurological Review
https://www.readbyqxmd.com/read/23448452/neurological-complications-of-anderson-fabry-disease
#14
REVIEW
Antonino Tuttolomondo, Rosaria Pecoraro, Irene Simonetta, Salvatore Miceli, Valentina Arnao, Giuseppe Licata, Antonio Pinto
Characteristic clinical manifestations of AFD such as acroparesthesias, angiokeratoma, corneal opacity, hypo/ and anhidrosis, gastrointestinal symptoms, renal and cardiac dysfunctions can occur in male and female patients, although heterozygous females with AFD usually seem to be less severely affected. The most prominent CNS manifestations consist of cerebrovascular events such as transient ischaemic attacks (TIAs) and (recurrent) strokes. For the most part, CNS complications in AFD have been attributed to cerebral vasculopathy, including anatomical abnormalities...
2013: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/23183236/melatonin-augments-hypothermic-neuroprotection-in-a-perinatal-asphyxia-model
#15
Nicola J Robertson, Stuart Faulkner, Bobbi Fleiss, Alan Bainbridge, Csilla Andorka, David Price, Elizabeth Powell, Lucy Lecky-Thompson, Laura Thei, Manigandan Chandrasekaran, Mariya Hristova, Ernest B Cady, Pierre Gressens, Xavier Golay, Gennadij Raivich
Despite treatment with therapeutic hypothermia, almost 50% of infants with neonatal encephalopathy still have adverse outcomes. Additional treatments are required to maximize neuroprotection. Melatonin is a naturally occurring hormone involved in physiological processes that also has neuroprotective actions against hypoxic-ischaemic brain injury in animal models. The objective of this study was to assess neuroprotective effects of combining melatonin with therapeutic hypothermia after transient hypoxia-ischaemia in a piglet model of perinatal asphyxia using clinically relevant magnetic resonance spectroscopy biomarkers supported by immunohistochemistry...
January 2013: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/23171224/methyl-isobutyl-amiloride-reduces-brain-lac-naa-cell-death-and-microglial-activation-in-a-perinatal-asphyxia-model
#16
Nicola J Robertson, Takenori Kato, Alan Bainbridge, Manigandan Chandrasekaran, Osuke Iwata, Andrew Kapetanakis, Stuart Faulkner, Jeanie Cheong, Sachiko Iwata, Mariya Hristova, Ernest Cady, Gennadij Raivich
Na⁺/H⁺ exchanger (NHE) blockade attenuates the detrimental consequences of ischaemia and reperfusion in myocardium and brain in adult and neonatal animal studies. Our aim was to use magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry to investigate the cerebral effects of the NHE inhibitor, methyl isobutyl amiloride (MIA) given after severe perinatal asphyxia in the piglet. Eighteen male piglets (aged < 24 h) underwent transient global cerebral hypoxia-ischaemia and were randomized to (i) saline placebo; or (ii) 3 mg/kg intravenous MIA administered 10 min post-insult and 8 hourly thereafter...
March 2013: Journal of Neurochemistry
https://www.readbyqxmd.com/read/22696041/apparent-diffusion-coefficient-restriction-in-the-white-matter-going-beyond-acute-brain-territorial-ischemia
#17
Valentina Citton, Alberto Burlina, Claudio Baracchini, Massimo Gallucci, Alessia Catalucci, Sandro Dal Pos, Alessandro Burlina, Renzo Manara
BACKGROUND: Reduction of apparent diffusion coefficient (ADC) values in white matter is not always ischaemic in nature. METHODS: We retrospectively analysed our MRI records featuring reduced ADC values in the centrum semiovale without grey matter involvement or significant vasogenic oedema. RESULTS: Several conditions showed the aforementioned MR findings: moose-horn lesions on coronal images in X-linked Charcot-Marie-Tooth disease; small fronto-parietal lesions in Menkes disease; marked signal abnormalities in the myelinised regions in the acute neonatal form of maple syrup urine disease; strip-like involvement of the corpus callosum in glutaric aciduria type 1; persistent periventricular parieto-occipital abnormalities in phenylketonuria; diffuse signal abnormalities with necrotic evolution in global cerebral anoxia or after heroin vapour inhalation; almost completely reversible symmetric fronto-parietal lesions in methotrexate neurotoxicity; chain-like lesions in watershed ischaemia; splenium involvement that normalises in reversible splenial lesions or leads to gliosis in diffuse axonal injury...
April 2012: Insights Into Imaging
https://www.readbyqxmd.com/read/22512781/neuroprotection-by-the-histone-deacetylase-inhibitor-trichostatin-a-in-a-model-of-lipopolysaccharide-sensitised-neonatal-hypoxic-ischaemic-brain-injury
#18
Bobbi Fleiss, Marie K L Nilsson, Klas Blomgren, Carina Mallard
BACKGROUND: Perinatal brain injury is complex and often associated with both inflammation and hypoxia-ischaemia (HI). In adult inflammatory brain injury models, therapies to increase acetylation are efficacious in reducing inflammation and cerebral injury. Our aim in the present study was to examine the neuropathological and functional effects of the histone deacetylase inhibitor (HDACi) trichostatin A (TSA) in a model of neonatal lipopolysaccharide (LPS)-sensitised HI. We hypothesised that, by decreasing inflammation, TSA would improve injury and behavioural outcome...
2012: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/22378919/executive-dysfunction-in-adults-with-moyamoya-disease-is-associated-with-increased-diffusion-in-frontal-white-matter
#19
Lionel Calviere, Guillaume Ssi Yan Kai, Isabelle Catalaa, Fabienne Marlats, Fabrice Bonneville, V Larrue
BACKGROUND AND PURPOSE: Alteration of the cerebrovascular reserve (CVR) in the frontal lobes has been associated with cognitive dysfunction in adults with moyamoya disease (MMD). Elevation of the apparent diffusion coefficient (ADC) in normal-appearing white matter on conventional MRI may occur as a consequence of chronic haemodynamic failure. In the present study, the authors examined the relation of ADC with CVR and cognitive dysfunction in adults with MMD. METHODS: The authors measured ADC and CVR in the normal-appearing frontal white matter...
June 2012: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/22217580/glutamate-receptors-the-cause-or-cure-in-perinatal-white-matter-injury
#20
R Douglas Fields
Glutamate toxicity from hypoxia-ischaemia during the perinatal period causes white matter injury that can result in long-term motor and intellectual disability. Blocking ionotropic glutamate receptors (GluRs) has been shown to inhibit oligodendrocyte injury in vitro, but GluR antagonists have not yet proven helpful in clinical studies. The opposite approach of activating GluRs on developing oligodendrocytes shows promise in experimental studies on rodents as reported by Jartzie et al., in this issue. Group I metabotropic glutamate receptors (mGluRs) are expressed transiently on developing oligodendrocytes in humans during the perinatal period, and the blood-brain-barrier permeable agonist of group I mGluRs, 1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD), reduces white matter damage significantly in a rat model of perinatal hypoxia-ischaemia...
November 2010: Neuron Glia Biology
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