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White matter injury

Gergely David, Maryam Seif, Eveline Huber, Markus Hupp, Jan Rosner, Volker Dietz, Nikolaus Weiskopf, Siawoosh Mohammadi, Patrick Freund
OBJECTIVE: To characterize remote secondary neurodegeneration of spinal tracts and neurons below a cervical spinal cord injury (SCI) and its relation to the severity of injury, the integrity of efferent and afferent pathways, and clinical impairment. METHODS: A comprehensive high-resolution MRI protocol was acquired in 17 traumatic cervical SCI patients and 14 controls at 3T. At the cervical lesion, a sagittal T2-weighted scan provided information on the width of preserved midsagittal tissue bridges...
February 15, 2019: Neurology
M-C Chou, J-Y Li, P-H Lai
BACKGROUND AND PURPOSE: Patients with carbon monoxide (CO) intoxication exhibit progressive WM changes that are not well-understood. The purpose of this study was to detect longitudinal WM changes using voxelwise diffusional kurtosis imaging in patients with CO intoxication from the acute-to-chronic stage after CO intoxication. MATERIALS AND METHODS: Twenty-four patients with CO intoxication and 21 age- and sex-matched healthy controls were enrolled in this study...
February 14, 2019: AJNR. American Journal of Neuroradiology
Monica Margoni, Maria Petracca, Simona Schiavi, Michelle Fabian, Aaron Miller, Fred D Lublin, Matilde Inglese
BACKGROUND: Diffuse white matter (WM) injury is prominent in primary progressive multiple sclerosis (PP-MS) pathology and is a potential biomarker of disease progression. Diffusion Kurtosis Imaging (DKI) allows the quantification of non-Gaussian water diffusion, providing metrics with high WM pathological specificity. OBJECTIVE: To characterize the pathological changes occurring in the normal appearing white matter (NAWM) of patients with PP-MS at baseline and at 1-year follow-up and to assess their impact on disability and short-term disease progression...
February 13, 2019: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Veronika Golubinskaya, Regina Vontell, Veena Supramaniam, Josephine Wyatt-Ashmead, Helena Gustafsson, Carina Mallard, Holger Nilsson
Bestrophin-3, a potential candidate for a calcium-activated chloride channel, recently was suggested to have cell-protective functions. We studied the expression and alternative splicing of bestrophin-3 in neonatal mouse brain and after hypoxic-ischemic (HI) injury and in human neonatal brain samples. HI brain injury was induced in 9-day old mice by unilateral permanent common carotid artery occlusion in combination with exposure to 10% oxygen for 50 min. Endoplasmic reticulum stress was induced by thapsigargin treatment in primary culture of mouse brain astrocytes...
2019: Frontiers in Physiology
Hao Liu, Nadya Povysheva, Marie E Rose, Zhiping Mi, Joseph S Banton, Wenjin Li, Fenghua Chen, Daniel P Reay, Germán Barrionuevo, Feng Zhang, Steven H Graham
Ubiquitin C-terminal hydrolase L1 (UCHL1) is a unique brain-specific deubiquitinating enzyme. Mutations in and aberrant function of UCHL1 have been linked to many neurological disorders. UCHL1 activity protects neurons from hypoxic injury, and binding of stroke-induced reactive lipid species to the cysteine 152 (C152) of UCHL1 unfolds the protein and disrupts its function. To investigate the role of UCHL1 and its adduction by reactive lipids in inhibiting repair and recovery of function following ischemic injury, a knock-in (KI) mouse expressing the UCHL1 C152A mutation was generated...
February 13, 2019: Proceedings of the National Academy of Sciences of the United States of America
Wei Liu, Ping-Hong Yeh, Dominic Nathan, Chihwa Song, Helena Wu, Grant H Bonavia, John M Ollinger, Gerard Riedy
Brain venous volume above the lateral ventricle in military patients with TBI was assessed using two segmentation approaches on susceptibility weighted images (SWI) and quantitative susceptibility maps (QSM). This retrospective study included a total of 147 subjects: 14 patients with severe TBI; 38 patients with moderate TBI; 58 patients with mild TBI (28 with blast related injuries and 30 with nonblast related injuries) and 37 control subjects without history of TBI. Using the multiscale vessel enhancement filter on SWI images, patients with severe TBI demonstrated significantly higher segmented venous volumes compared to the controls...
February 14, 2019: Journal of Neurotrauma
Chen-Guang Yu, Vimala Bondada, Sarbani Ghoshal, Ranjana Singh, Christina K Pistilli, Kavi Dayaram, Hina Iqbal, Madison Sands, Kate Davis, Subbarao Bondada, James W Geddes
We previously reported the serendipitous observation that Fenbendazole, a benzimidazole anthelmintic, improved functional and pathological outcomes following thoracic spinal cord contusion injury in mice when administered pre-injury. Fenbendazole is widely used in veterinary medicine. However, it is not approved for human use and it was uncertain if only post-injury administration would offer similar benefits. In the present study we evaluated post-injury administration of a closely related, human anthelmintic drug, Flubendazole, using a rat spinal cord contusion injury model...
February 12, 2019: Journal of Neurotrauma
Megan Finch-Edmondson, Catherine Morgan, Rod W Hunt, Iona Novak
Worldwide, an estimated 15 million babies are born preterm (<37 weeks' gestation) every year. Despite significant improvements in survival rates, preterm infants often face a lifetime of neurodevelopmental disability including cognitive, behavioral, and motor impairments. Indeed, prematurity remains the largest risk factor for the development of cerebral palsy. The developing brain of the preterm infant is particularly fragile; preterm babies exhibit varying severities of cerebral palsy arising from reductions in both cerebral white and gray matter volumes, as well as altered brain microstructure and connectivity...
2019: Frontiers in Physiology
Michael Hayman, Gerda van Wezel-Meijler, Henrica van Straaten, Eva Brilstra, Floris Groenendaal, Linda S de Vries
BACKGROUND: Punctate white matter lesions (PWMLs) are small focal patches of increased signal intensity (SI) on T1- and decreased SI on T2-weighted magnetic resonance imaging (MRI). To date, there have been few reports of PWMLs in term born infants. OBJECTIVE: To identify associated diagnoses and factors predictive of clinical outcome in (near) term infants with PWMLs. METHODS: MRI studies and clinical records of (near) term infants, with PWMLs on MRI scans performed in two institutions in the first 28 postnatal days were reviewed...
January 26, 2019: European Journal of Paediatric Neurology: EJPN
A Scott Emmert, Shawn M Vuong, Crystal Shula, Diana Lindquist, Weihong Yuan, Yueh-Chiang Hu, Francesco T Mangano, June Goto
OBJECTIVEEmergence of CRISPR/Cas9 genome editing provides a robust method for gene targeting in a variety of cell types, including fertilized rat embryos. The authors used this method to generate a transgenic rat L1cam knockout model of X-linked hydrocephalus (XLH) with human genetic etiology. The object of this study was to use diffusion tensor imaging (DTI) in studying perivascular white matter tract injury in the rat model and to characterize its pathological definition in histology.METHODSTwo guide RNAs designed to disrupt exon 4 of the L1cam gene on the X chromosome were injected into Sprague-Dawley rat embryos...
February 8, 2019: Journal of Neurosurgery
Ran Li, Poornima Venkat, Michael Chopp, Qiang Zhang, Tao Yan, Jieli Chen
Subarachnoid hemorrhage (SAH) results in neurological damage, acute cardiac damage and has a high mortality rate. Immunoresponse in the acute phase after SAH plays a key role in mediating vasospasm, edema, inflammation and neuronal damage. The S1P/S1PR pathway impacts multiple cellular functions, exerts anti-inflammatory and anti-apoptotic effects, promotes remyelination, and improves outcome in several central nervous system (CNS) diseases. RP001 hydrochloride is a novel S1PR agonist, which sequesters lymphocytes within their secondary tissues and prevents infiltration of immune cells into the CNS thereby reducing immune response...
February 5, 2019: Journal of the Neurological Sciences
Xiaoyun Gou, Ying Tang, Yi Qu, Dongqiong Xiao, Junjie Ying, Dezhi Mu
White matter injury (WMI) prevents the normal development of myelination, leading to central nervous system myelination disorders and the production of chronic sequelae associated with WMI, such as chronic dyskinesia, cognitive impairment and cerebral palsy. This results in a large emotional and socioeconomic burden. Decreased myelination in preterm infant WMI is associated with the delayed development or destruction of oligodendrocyte (OL) lineage cells, particularly oligodendrocyte precursor cells (OPCs)...
February 9, 2019: Reviews in the Neurosciences
Robert G Briggs, Dillon P Pryor, Andrew K Conner, Cameron E Nix, Camille K Milton, Joseph K Kuiper, Ali H Palejwala, Michael E Sughrue
BACKGROUND: Arterial disruption during brain surgery can cause devastating injuries to wide expanses of white and grey matter far beyond the tumor resection cavity. Such damage may occur as a result of disrupting blood flow through "en passage" arteries. Identification of these arteries is critical to prevent unforeseen neurologic sequelae during brain tumor resection. In this study, we discuss one such artery, termed the artery of aphasia (AoA), which when disrupted can lead to receptive and expressive language deficits...
February 5, 2019: World Neurosurgery
Sung Ho Jang, You Sung Seo
RATIONALE: Headache is the most common physical complaint reported by the following traumatic brain injury (TBI). Several studies using diffusion tensor tractography (DTT) have demonstrated that injury of the spinothalamic tract (STT) is a pathogenetic mechanism of central pain following TBI. However, no study of headache due to injury of the STT has been reported. PATIENT CONCERNS: Patient 1 was a 52-year-old female who suffered head trauma resulting from an in-car traffic crash...
February 2019: Medicine (Baltimore)
G Fadda, R A Brown, R Magliozzi, B Aubert-Broche, J O'Mahony, R T Shinohara, B Banwell, R A Marrie, E A Yeh, L D Collins, D L Arnold, A Bar-Or
OBJECTIVE: Central nervous system (CNS) pathology in multiple sclerosis includes both focal inflammatory perivascular injury and injury to superficial structures, including the subpial region of the cortex, which reportedly exhibits a gradient of damage from the surface inwards. We assessed how early in the multiple sclerosis course a 'surface-in' process of injury suggesting progressive biology may begin. METHODS: We focused on the thalamus which notably has both a cerebrospinal fluid (CSF) interface and a white matter interface...
February 4, 2019: Annals of Neurology
Prakasham Rumajogee, Svetlana Altamentova, Lijun Li, Junyi Li, Jian Wang, Alan Kuurstra, Mohamad Khazaei, Stephanie Beldick, Ravi S Menon, Derek van der Kooy, Michael G Fehlings
Cerebral palsy (CP) is a common pediatric neurodevelopmental disorder, frequently resulting in motor and developmental deficits and often accompanied by cognitive impairments. A regular pathobiological hallmark of CP is oligodendrocyte maturation impairment resulting in white matter (WM) injury and reduced axonal myelination. Regeneration therapies based on cell replacement are currently limited, but neural precursor cells (NPCs), as cellular support for myelination, represent a promising regeneration strategy to treat CP, although the transplantation parameters (e...
September 2018: ENeuro
Isabella Wimmer, Cornelia Scharler, Tobias Zrzavy, Taro Kadowaki, Verena Mödlagl, Kim Rojc, Anna R Tröscher, Maja Kitic, Shuichi Ueda, Monika Bradl, Hans Lassmann
Human inflammatory or neurodegenerative diseases, such as progressive multiple sclerosis (MS), occur on a background of age-related microglia activation and iron accumulation as well as pre-existing neurodegeneration. Most experimental models for CNS diseases, however, are induced in rodents, which are naturally characterized by a homeostatic microglia phenotype, low cellular iron load and absence of neurodegeneration. Here, we show that naïve LEWzizi rats - Lewis rats with a zitter rat background - show a spontaneous phenotype partly mimicking the changes seen in human aging and particularly in the normal-appearing white and grey matter of patients with progressive MS...
January 31, 2019: Acta Neuropathologica Communications
Jianhua Peng, Jinwei Pang, Lei Huang, Budbazar Enkhjargal, Tongyu Zhang, Jun Mo, Pei Wu, Weilin Xu, Yuchun Zuo, Jun Peng, Gang Zuo, Ligang Chen, Jiping Tang, John H Zhang, Yong Jiang
White matter injury (WMI) is associated with motor deficits and cognitive dysfunctions in subarachnoid hemorrhage (SAH) patients. Therapeutic strategy targeting WMI would likely improve the neurological outcomes after SAH. Low-density lipoprotein receptor-related protein-1 (LRP1), a scavenger receptor of apolipoprotein E (apoE), is able to modulate microglia polarization towards anti-inflammatory M2 phenotypes during inflammatory and oxidative insult. In the present study, we investigated the effects of LRP1 activation on WMI and underlying mechanisms of M2 microglial polarization in a rat model of SAH...
January 23, 2019: Redox Biology
Erlan Sanchez, Héjar El-Khatib, Caroline Arbour, Christophe Bedetti, Hélène Blais, Karine Marcotte, Andrée-Ann Baril, Maxime Descoteaux, Danielle Gilbert, Julie Carrier, Nadia Gosselin
The restorative function of sleep partly relies on its ability to deeply synchronize cerebral networks to create large slow oscillations observable with EEG. However, whether a brain can properly synchronize and produce a restorative sleep when it undergoes massive and widespread white matter damage is unknown. Here, we answer this question by testing 23 patients with various levels of white matter damage secondary to moderate to severe traumatic brain injuries (ages 18-56; 17 males, six females, 11-39 months post-injury) and compared them to 27 healthy subjects of similar age and sex...
January 28, 2019: Brain: a Journal of Neurology
Anne Nack, Matthias Brendel, Julia Nedelcu, Markus Daerr, Stella Nyamoya, Cordian Beyer, Carola Focke, Maximilian Deussing, Chloé Hoornaert, Peter Ponsaerts, Christoph Schmitz, Peter Bartenstein, Axel Rominger, Markus Kipp
Positron emission tomography (PET) ligands targeting the translocator protein (TSPO) represent promising tools to visualize neuroinflammation in multiple sclerosis (MS). Although it is known that TSPO is expressed in the outer mitochondria membrane, its cellular localization in the central nervous system under physiological and pathological conditions is not entirely clear. The purpose of this study was to assess the feasibility of utilizing PET imaging with the TSPO tracer, [18F]-GE180, to detect histopathological changes during experimental demyelination, and to determine which cell types express TSPO...
January 28, 2019: Cells
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