Marc R Del Bigio

Marc R Del Bigio
University of Manitoba | UMN · Department of Pathology

MD PhD FRCPC

About

339
Publications
34,275
Reads
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11,924
Citations
Citations since 2017
60 Research Items
3501 Citations
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20172018201920202021202220230100200300400500600
20172018201920202021202220230100200300400500600
20172018201920202021202220230100200300400500600
Additional affiliations
January 2002 - present
Shared Health Manitoba
Position
  • neuropathologist
July 1994 - present
University of Manitoba
July 1994 - present

Publications

Publications (339)
Article
Full-text available
Background Gangliocytomas are rare neuronal tumors with an incidence of <1% of all central nervous system (CNS) neoplasms. They occur mostly in the pediatric age group, localizing within the cerebral cortex, most often the temporal lobe. Case Description We report a case of an intracranial gangliocytoma arising within the lateral ventricle in a 66...
Article
Full-text available
Malignant gliomas derive from brain glial cells and represent >75% of primary brain tumors. This includes anaplastic astrocytoma (grade III; AS), the most common and fatal glioblastoma multiforme (grade IV; GBM), and oligodendroglioma (ODG). We have generated patient-derived AS, GBM, and ODG cell models to study disease mechanisms and test patient-...
Article
Full-text available
Rett Syndrome (RTT) is a rare and progressive neurodevelopmental disorder that is caused by de novo mutations in the X-linked Methyl CpG binding protein 2 (MECP2) gene and is subjected to X-chromosome inactivation. RTT is commonly associated with neurological regression, autistic features, motor control impairment, seizures, loss of speech and purp...
Article
Introduction and objectives Rett Syndrome (RTT) is a neurodevelopmental disorder caused by Methyl CpG Binding Protein 2 (MECP2) gene mutations. Previous studies of MeCP2 in the human brain showed variable and inconsistent mosaic‐pattern immunolabelling, which has been interpreted as a reflection of activation‐state variability. We aimed to study po...
Poster
Reduced intracranial pulse pressure possibly mitigates development of acute hydrocephalus
Article
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Background Based upon experimental animal studies, the neurodevelopmental abnormalities associated with prenatal alcohol exposure (PNAE)/fetal alcohol spectrum disorder (FASD) have been attributed, at least in part, to epigenetic modifications. However, there are no direct analyses of human brain tissue. Methods Immunohistochemical detection of gl...
Article
Full-text available
The cover image is based on the Original Article A homozygous canonical splice acceptor site mutation in PRUNE1 is responsible for a rare childhood neurodegenerative disease in Manitoba Cree families by Jessica N. Hartley et al., DOI: 10.1002/ajmg.a.60690.
Article
Full-text available
Background Epigenetic (including DNA and histone) modifications occur in a variety of neurological disorders. If epigenetic features of brain autopsy material are to be studied, it is critical to understand the post-mortem stability of the modifications. Methods Pig and mouse brain tissue were formalin-fixed and paraffin-embedded, or frozen after...
Article
Full-text available
Rett syndrome (RTT) is a severe and rare neurological disorder that is caused by mutations in the X-linked MECP2 (methyl CpG-binding protein 2) gene. MeCP2 protein is an important epigenetic factor in the brain and in neurons. In Mecp2-deficient neurons, nucleoli structures are compromised. Nucleoli are sites of active ribosomal RNA (rRNA) transcri...
Data
Primary omission control for murine cerebellum. Primary antibody omission in wild-type male and female (A,C) and mutant homozygote (B) or heterozygote (D) mice.
Data
Quantification of nuclear histone H3 and H3 di-acetylation at K9–K14 (H3AC) and cytoplasmic S100 normalized to GAPDH in Rett syndrome cerebellum and controls. (A,B) Western blot (WB) quantification of nuclear cell extracts of controls and RTT patients individually and in combination, respectively. The data are shown with the following samples in th...
Data
Detection of nucleolin protein in the cerebellum of R255X Rett syndrome (RTT) patients. (A,B) Microscopic images of post-mortem human cerebellum for nucleolin (red) and DAPI signals (white) in two female controls (a–c), and primary omission (d,e). (C,D) Microscopic images of post-mortem human cerebellum for nucleolin (red) and DAPI signals (white)...
Data
The mTOR and P70S6K signaling molecules in Rett syndrome. Representative Western blots (WB) with total cell extract of a human control and a G451T RTT cerebellum with indicated antibodies (mTOR, phosphorylated mTOR at Serine 2481 or 2448, G-Beta-L as the common component of mTOR complexes, Raptor as part of mTORC1, and Rictor as part of mTORC2), P7...
Data
Brain sample characteristics for rett syndrome (RTT) patients and controls.
Data
Secondary antibodies used for Western blot (WB) or immunohistochemistry (IHC).
Data
Primary antibodies used for Western blot (WB) or immunohistochemistry (IHC).
Article
Autosomal recessive PRUNE1 mutations are reported to cause a severe neurodevelopmental disorder with microcephaly, hypotonia, and brain malformations. We describe clinical and neuropathological features in a cohort of nine individuals of Cree descent who, because of a founder effect, are homozygous for the same PRUNE1 mutation. They follow the cour...
Article
Full-text available
Prior research on 3-week hydrocephalic rats showed that behavioral deficits and white matter damage could be reduced by treatment with Ca2+ channel blocker nimodipine. We hypothesized that treatment with nimodipine would be also beneficial to young ferrets with kaolin-induced hydrocephalus. Hydrocephalus was induced at 14 days of age and animals we...
Article
Full-text available
Human brain development proceeds via a sequentially transforming stem cell population in the ventricular-subventricular zone (V-SVZ). An essential, but understudied, contributor to V-SVZ stem cell niche health is the multi-ciliated ependymal epithelium, which replaces stem cells at the ventricular surface during development. However, reorganization...
Article
Forensic pathologists encounter hypoxic-ischemic (HI) brain damage or traumatic brain injuries (TBI) on an almost daily basis. Evaluation of the findings guides decisions regarding cause and manner of death. When there are gross findings of brain trauma, the cause of death is often obvious. However, microscopic evaluation should be used to augment...
Article
Toluene is an organic solvent used in industry and as a substance of abuse. The latter situation may be associated with a leukoencephalopathy characterized by white matter atrophy, multifocal myelin loss, and macrophages that contain birefringent granular inclusions. To determine if rodents can develop the same white matter damage, we studied archi...
Chapter
Full-text available
This chapter focuses on the pathology of hydrocephalus in children. With respect to causes of hydrocephalus, an anatomical approach is used highlighting abnormalities that can impede cerebrospinal fluid movements at the interventricular foramina, the cerebral aqueduct, the fourth ventricular apertures, and the subarachnoid space. Inflammatory proce...
Article
The extensive heterogeneity both between and within the medulloblastoma (MB) subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH MB subgroup. Here, we demonstrate the utility o...
Article
Memantine is a selective, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that has previously been shown to have neuroprotective qualities in some animal models of neurologic disease. We hypothesized that memantine therapy would improve behavioral, neuropathological, and/or biochemical outcomes in juvenile rats with kaolin-induced h...
Data
Fig. S1. Knockdown of OTX2 in Group 3 and Group 4 MB decreases tumorsphere formation and self‐renewal. Fig. S2. Semaphorin genes are negatively correlated with OTX2 expression in Group 3 and Group 4 MB cells. Fig. S3. Axon guidance gene expression is upregulated following OTX2 knockdown in Group 3 and Group 4 MB cells. Fig. S4. Recombinant semap...
Chapter
This chapter confines to the discussion of hemorrhagic lesions that occur in utero or in the perinatal period. It focuses on regions of immature brain prone to hemorrhage and the brain vasculature. Identification of hemorrhage depends on in vivo imaging or autopsy examination. The main risk factors for intraventricular hemorrhage (IVH) are young ge...
Chapter
Cell bodies of neurons reside throughout the central nervous system. Hypoxic-ischemic damage, sometimes called asphyxia, is one of the main causes of neonatal encephalopathy; the dysfunctional state is called hypoxic-ischemic encephalopathy. This chapter focuses on patterns of neuronal damage following deprivation of energy supplies, and the modify...
Article
Full-text available
Medulloblastoma (MB) is the most common malignant primary pediatric brain cancer. Among the most aggressive subtypes, Group 3 and Group 4 originate from stem/progenitor cells, frequently metastasize, and often display the worst prognosis, yet we know the least about the molecular mechanisms driving their progression. Here, we show that the transcri...
Article
The extensive heterogeneity within the medulloblastoma (MB) molecular variants has revealed a critical need for subtype-specific biomarkers and therapeutic strategies. Using a high throughput flow cytometry screen and gain/loss of function studies, we previously identified CD271/p75NTR as a candidate stem/progenitor cell marker specifically in SHH...
Article
Primary CNS diffuse large B-cell lymphoma (PCNS-DLBCL) and systemic DLBCL harbor mutations in MYD88 and CD79B. DNA methyltransferase (MGMT) is methylated in some DLBCL. Our goal was to investigate the frequencies of these events, which have not been previously reported within the same series of patients with PCNS-DLBCL. Fifty-four cases of PCNS-DLB...
Article
Full-text available
Fetal alcohol spectrum disorder (FASD) is a common neurodevelopmental problem, but neuropathologic descriptions are rare and focused on the extreme abnormalities. We conducted a retrospective survey (1980-2016) of autopsies on 174 individuals with prenatal alcohol exposure or an FASD diagnosis. Epidemiologic details and neuropathologic findings wer...
Article
Background: Sporadic progressive ataxia and palatal tremor is a rare syndrome characterized by mid- to late-adult-onset symptomatic palatal tremor and slowly progressive cerebellar ataxia. To date, there has been only one autopsy report, which described a novel 4-repeat tauopathy with hypertrophic olivary degeneration and tau-positive inclusions i...
Article
Medulloblastoma (MB) is the most common malignant primary brain tumor and is currently classified into 5 distinct molecular subtypes based on genomic alterations, gene expression profile, response to treatment and cell of origin. This extensive heterogeneity has revealed a critical need for subtype-specific, functionally validated biomarkers and th...
Article
Full-text available
Group-3 Medulloblastomas (MBL) has the worst prognosis due to its resistance to radiation and chemotherapy with a 5-year survival of 30%. Thus, there is an urgent need to elucidate targets that can sensitize Group-3 tumors to conventional treatments. We identified PRDX1 as a candidate therapeutic target for therapy sensitization in group-3 tumors....
Article
Full-text available
The human superoxide dismutase 1 (SOD1) gene is responsible for neutralizing supercharged oxygen radicals within the cell. Mutation in SOD1 gene causes amyotrophic lateral sclerosis (ALS). Recent studies have shown involvement of the cerebellum in ALS, although the cerebellar contribution in SOD1 transgenic mice remains unclear. Using immunohistopa...
Data
SOD1 expression is localized in Purkinje cell layer of wt SOD1 Tg mice and human cerebella. (A) A transverse cryostat sections through the lobule VI of the 8 month control mouse cerebellum immunostained with anti-SOD1 shows lack of SOD1 expression in Purkinje cell soma; shown at a higher magnification in “(a).” (B,C) A transverse section through th...
Article
The presence of hemosiderin in the optic nerve sheath and/or retina is sometimes used to estimate the timing of injury in infants or children with suspected non-accidental head trauma. To determine the prevalence of hemosiderin in deaths not associated with trauma, we performed a prospective study of retroocular orbital tissue, cranial convexity, a...
Article
Full-text available
Background Hydranencephaly is a congenital anomaly leading to replacement of the cerebral hemispheres with a fluid-filled cyst. The goals of this work are to describe a novel autosomal-recessive syndrome that includes hydranencephaly (multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly (MARCH)); to ident...
Article
Progressive ataxia and palatal tremor: 2 autopsy cases of a novel tauopathy - Volume 44 Issue S1 - A.F. Gao, M. Al-Murshed, M. Del Bigio, A. Socher, A.E. Lang, D.G. Munoz
Article
div class="title">Community Health Consequences of a Second-Impact Syndrome Death Following Concussion - Carly Scramstad, Michael J. Ellis, Marc R. Del Bigio
Article
Chronic traumatic encephalopathy (CTE) has been described mainly in professional athletes and military personnel and is characterized by deposition of hyperphosphorylated tau at the depths of cortical sulci and around blood vessels. To assess CTE-like changes in a routine neuropathology service, we prospectively examined 111 brains (age 18–60 years...
Article
Full-text available
Medulloblastoma (MB) is the most common malignant primary brain tumor in children. Despite improved clinical outcomes, children with MB often suffer from consequences of treatment such as surgery, chemotherapy and radiation. MB is currently classified into 4 distinct molecular subtypes based on genomic alterations, gene expression profiles, respons...
Article
Menkes disease is a rare, X-linked recessive disorder of the ATP7A gene, a copper transporter; resulting in systemic copper deficiency. The deficient function of copper-dependent enzymes manifests clinically with failure to thrive, seizures, hypotonia, coarse hair, connective tissue abnormalities, and neurodegeneration. Cerebral arteries are often...
Article
Full-text available
Background Previous work with 3-week hydrocephalic rats showed that white matter damage could be reduced by the calcium channel antagonist magnesium sulfate (MgSO4). We hypothesized that MgSO4 therapy would improve outcomes in ferrets with hydrocephalus induced with kaolin at 15 days. Methods MRI was performed at 29 days to assess ventricle size a...
Chapter
Chronic abuse of certain solvents or glues by inhalation is associated with white matter damage in the central nervous system. The damage is characterized by patchy perivascular myelin loss and accumulation of microglia/macrophages with characteristic lamellar inclusion material. Neurons and axons are generally spared. Based on the various substanc...
Article
Full-text available
Pharmacological interventions have been tested experimentally and clinically to prevent hydrocephalus and avoid the need for shunting beginning in the 1950s. Clinical trials of varied quality have not demonstrated lasting and convincing protective effects through manipulation of cerebrospinal fluid production, diuresis, blood clot fibrinolysis, or...
Article
Full-text available
Major research efforts have focused on defining cell surface marker profiles for characterization and selection of brain tumor stem/progenitor cells. Medulloblastoma is the most common primary malignant pediatric brain cancer and consists of 4 molecular subgroups: WNT, SHH, Group 3 and Group 4. Given the heterogeneity within and between medulloblas...
Article
Perinatal intracerebral hemorrhage, also known as germinal matrix hemorrhage (GMH), refers to the bleeding that arises from the sub-ependymal (or periventricular) germinal region of the immature brain. Intraventricular hemorrhage (IVH) refers to the bleeding that extends into the ventricles, usually as an extension of GMH. Clinical studies have sho...
Article
Full-text available
Background Previous work with 3-week hydrocephalic rats showed that white matter damage could be reduced by the calcium channel antagonist magnesium sulfate (MgSO4). We hypothesized that MgSO4 therapy would improve outcomes in ferrets with hydrocephalus induced with kaolin at 15 days.
Article
Full-text available
Medulloblastoma (MB) is the most common malignant primary pediatric brain tumor and is currently divided into 4 subtypes based on different genomic alterations, gene expression profiles and response to treatment: WNT, Sonic Hedgehog (SHH), Group 3 and Group 4. This extensive heterogeneity has made it difficult to assess the functional relevance of...
Conference Paper
Full-text available
Medulloblastoma (MB) is the most common malignant primary pediatric brain tumor and is currently divided into 4 subtypes based on different genomic alterations, gene expression profiles and response to treatment: Wnt, Sonic Hedgehog (Shh), Group 3 and Group 4. This extensive heterogeneity has made it difficult to assess the functional relevance of...
Article
Full-text available
Major research efforts have focused on the isolation and characterization of brain tumor stem cells, or propagating cells (BTPC) in a variety of brain cancers. Elucidating cell surface marker profiles that can be used to selectively isolate this cellular population is an imperative first step in the development of targeted therapies. Medulloblastom...
Article
Bowen-Conradi syndrome (BCS) is a ribosomopathy characterized by severe developmental delay and growth failure that typically leads to death by one year of age. It is caused by a c.257A>G p.D86G substitution in the ribosomal biogenesis protein, Essential for Mitotic Growth 1 (EMG1). We generated a knock-in of the D86G substitution in mice to charac...
Article
Full-text available
Background Prior work showed that whole blood, plasma, and serum injections are damaging to the neonatal rodent brain in a model of intracerebral / periventricular hemorrhage. Thrombin alone is also damaging. In adult animal models of hemorrhagic stroke, the protease-activated (thrombin) receptor PAR1 mediates some of the brain damage. We hypothesi...
Article
Full-text available
The mammalian cerebellum is located in the posterior cranial fossa and is critical for motor coordination and non-motor functions including cognitive and emotional processes. The anatomical structure of cerebellum is distinct with a three-layered cortex. During development, neurogenesis and fate decisions of cerebellar primordium cells are orchestr...
Article
Full-text available
Optic chiasm lesions in myelin oligodendrocyte glycoprotein (MOG)–experimental autoimmune encephalomyelitis (EAE) mice were characterized using magnetic resonance imaging (MRI) and validated using electron microscopy (EM). MR images were collected from 3 days after induction to remission, approximately 20 days after induction. Hematoxylin and eosin...
Article
Full-text available
Epigenetics refers to a variety of processes that have heritable effects on gene expression programs without changes in DNA sequence. Key players in epigenetic control are chemical modifications to DNA, histone, and non-histone chromosomal proteins, which establish a complex re