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white matter ischaemia

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/22048857/-retrospective-analysis-of-routine-mri-and-correlation-with-aetiology-of-dementia-severity-and-neuropsychology-in-a-memory-clinic-population
#16
S Merkle, S Kreil, G Suttner, M Doelken, A Dörfler, T Richter-Schmidinger, J Kornhuber, M Weih
BACKGROUND: The contribution of potential treatable dementia aetiologies diagnosed using cerebral imaging varied considerably in previous studies and was not evaluated in a recent larger German sample of patients from a memory clinic. MATERIAL AND METHODS: MRI images of 502 patients were retrospectively reassessed. Beside the proportion of potentially treatable dementia aetiology, the extent of whole brain atrophy (semiquantitative) and vascular white matter lesions were assessed...
November 2011: Fortschritte der Neurologie-Psychiatrie
https://www.readbyqxmd.com/read/21776363/fabry-disease-and-early-stroke
#17
U Feldt-Rasmussen
Fabry disease, an X-linked lysosomal storage disorder, results from deficient activity of the enzyme α-galactosidase A. Affected males with the classic phoenotype have acroparaesthesias, hypohidrosis, and corneal opacities in childhood and develop renal failure, cardiac hypertrophy or strokes in the third to fifth decade of life. Some female heterozygotes are asymptomatic, some as severely affected as males. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders...
2011: Stroke Research and Treatment
https://www.readbyqxmd.com/read/20935330/heterogeneity-of-small-vessel-disease-a-systematic-review-of-mri-and-histopathology-correlations
#18
REVIEW
Alida A Gouw, Alexandra Seewann, Wiesje M van der Flier, Frederik Barkhof, Annemieke M Rozemuller, Philip Scheltens, Jeroen J G Geurts
BACKGROUND: White matter hyperintensities (WMH), lacunes and microbleeds are regarded as typical MRI expressions of cerebral small vessel disease (SVD) and they are highly prevalent in the elderly. However, clinical expression of MRI defined SVD is generally moderate and heterogeneous. By reviewing studies that directly correlated postmortem MRI and histopathology, this paper aimed to characterise the pathological substrates of SVD in order to create more understanding as to its heterogeneous clinical manifestation...
February 2011: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/20673845/subtle-white-matter-injury-is-common-in-term-born-infants-with-a-wide-range-of-risks
#19
Sachiko Iwata, Alan Bainbridge, Tomohiko Nakamura, Masanori Tamura, Sachio Takashima, Toyojiro Matsuishi, Osuke Iwata
OBJECTIVES: Perinatal hypoxia-ischaemia affects cognitive outcomes of infants even when clinical symptoms were latent and intensive care was not required. We performed a retrospective analysis in a cohort of term infants who required intensive care (i) to investigate the incidence of abnormal white matter appearances on the magnetic resonance imaging obtained before 2 months corrected age, and (ii) to examine its relationships with other cerebral lesions, clinical backgrounds, and short-term outcome at 12 months...
November 2010: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/20512322/mr-imaging-of-term-infants-with-hypoxic-ischaemic-encephalopathy-as-a-predictor-of-neurodevelopmental-outcome-and-late-mri-appearances
#20
Eilish Twomey, Anne Twomey, Stephanie Ryan, John Murphy, Veronica B Donoghue
BACKGROUND: Morbidity attributable to hypoxic-ischaemic injury (HIE) in the perinatal period remains problematic, and timely and accurate assessment of the degree of injury is required for clinical management and prognosis. Conventional MR sequences typically appear normal in the first 48 h post HIE. While diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps register the injury earlier, perhaps within the first 24 h, it has been suggested that there may be a propensity at that early stage to underestimate the lesion severity or extent...
September 2010: Pediatric Radiology
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