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Journal of Neuropathology and Experimental Neurology

Alessandro Giuliani, Sandra Sivilia, Vito Antonio Baldassarro, Marco Gusciglio, Luca Lorenzini, Michele Sannia, Laura Calzà, Luciana Giardino
We describe age-related histological structure and molecular changes of the neurovascular unit (NVU) in the cerebral cortex of Tg2576 and age-matched wild-type (WT) mice. Major results can be summarized as follows: (i) β-amyloid (6E10)-immunoreactivity progressively increases in neurons and astrocytes of Tg2576 mice, reaching the highest concentration at 5 months and then decreasing as soon as extracellular plaque deposition begins; (ii) the synaptic puncta density of glutamatergic and GABAergic neurons in Tg2576 mice is unbalanced versus WT at all investigated ages, with a decrease in synaptophysin and VGLUT1; density of VGAT contacts is higher in 27-month-old Tg2576 versus WT mice; (iii) capillary density is higher in 5-month-old Tg2576 versus WT mice, then decreases to a lower density at 27 months, when the capillary-astrocyte interface is lower; and (iv) mRNA expression of genes involved in microvessel dynamics indicates age- and genotype-dependent changes in the expression levels of hypoxia-related genes, i...
January 9, 2019: Journal of Neuropathology and Experimental Neurology
Chenyue Xu, Luning Mao, Ji Xiong, Jianbo Wen, Yin Wang, Daoying Geng, Ying Liu
Significant angiogenesis is one of the malignant features in astrocytomas. Cotransfactor Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) is a major regulator of embryonic angiogenesis, in which it plays an essential role in vascular tip cell migration, blood vessel formation, and vascular barrier maturation. We quantified TAZ expression on blood vessels and parenchyma of astrocytomas of varying malignancy to investigate its role in tumor angiogenesis. Replicating others' findings, we observed that TAZ is expressed in tumor cells but also in vascular cells...
January 4, 2019: Journal of Neuropathology and Experimental Neurology
Giovanni Cirillo, Mario Cirillo, Fivos Panetsos, Assunta Virtuoso, Michele Papa
Selective neuronal death in neurodegenerative disorders represents the final step of a cascade of events, including neuroinflammation, regional-specific reactive gliosis, changes of brain-blood barrier structure and functions, metabolic failure and mitochondrial energy impairment. Bilateral striatal necrosis is usually reported in inherited mitochondrial disorders, suggesting a pathogenetic role of the energy impairment by mitochondrial dysfunction. We investigated mechanisms of the selective striatal degeneration, comparing clinical findings of a patient with an acquired bilateral striatal necrosis and experimental data of a selective basal ganglia degenerative model in rats...
January 3, 2019: Journal of Neuropathology and Experimental Neurology
John W Prineas, Sandra Lee
There are reports that astrocyte perivascular endfeet are damaged in some cases of multiple sclerosis (MS). This study was designed to determine the origin and outcome of astrocyte damage in acute, resolving, and inactive plaques. Ten acute plaques from 10 early MS cases and 14 plaques of differing histological age from 9 subacute and chronic cases were examined immunohistochemically. Also examined were nonnecrotic early lesions in 3 patients with neuromyelitis optica (NMO). Plaques from 3 MS cases were examined electron microscopically...
January 3, 2019: Journal of Neuropathology and Experimental Neurology
Jennifer A Tinklenberg, Emily M Siebers, Margaret J Beatka, Brittany A Fickau, Samuel Ayres, Hui Meng, Lin Yang, Pippa Simpson, Henk L Granzier, Michael W Lawlor
Mutations in at least 12 genes are responsible for a group of congenital skeletal muscle diseases known as nemaline myopathies (NMs). NMs are associated with a range of clinical symptoms and pathological changes often including the presence of cytoplasmic rod-like structures (nemaline bodies) and myofiber hypotrophy. Our recent work has identified a variable degree of behavioral benefit when treating 2 NM mouse models due to mutations in Acta1 with myostatin inhibition. This study is focused on the effects of delivering ActRIIB-mFc (Acceleron; a myostatin inhibitor) to the nebulin conditional knockout KO (Neb cKO) mouse model of NM...
December 29, 2018: Journal of Neuropathology and Experimental Neurology
Bing Chun Yan, Jie Wang, Yanggang Rui, Jianwen Cao, Pei Xu, Dan Jiang, Xiaolu Zhu, Moo-Ho Won, Ping Bo, Peiqing Su
Gabapentin (GBP), an analgesic, adjunct antiepileptic, and migraine prophylactic drug, reduces neuronal injury induced by cerebral ischemia reperfusion (IR). However, the underlying biological molecular mechanism of GBP neuroprotection is not clear. In this study, we confirmed that dose-dependent (75 and 150 mg/kg) GBP treatment could significantly reduce IR-induced neuronal death. IR-induced neuronal death was inhibited by pretreatment with 150 mg/kg GBP in a middle cerebral artery occlusion rat model...
December 29, 2018: Journal of Neuropathology and Experimental Neurology
Joshua Schwartzenburg, Meredith Juncker, Ryan Reed, Shyamal Desai
Veterans who have served in the military are at a nearly 60% greater risk of being diagnosed with amyotrophic lateral sclerosis (ALS). Literature reports suggest that a history of traumatic brain injury (TBI) may be a risk factor for ALS in veterans. However, no diagnostic biomarkers are available for identifying ALS risk/development in TBI-exposed veterans. Here, using a Wes assay, we show that ISGylation, a conjugated form of interferon-stimulated gene 15 protein, is significantly elevated in the lumbar spinal cords (SC-Ls) of TBI-ALS compared with ALS veterans without a previous history of TBI (nonTBI-ALS)...
December 28, 2018: Journal of Neuropathology and Experimental Neurology
Ekta Vasita, Saiqa Yasmeen, Joycelyn Andoh, Leslie R Bridges, Christina Kruuse, Mathilde M H Pauls, Anthony C Pereira, Atticus H Hainsworth
Cerebral small vessel disease in deep penetrating arteries is a major cause of lacunar infarcts, white matter lesions and vascular cognitive impairment. Local cerebral blood flow in these small vessels is controlled by endothelial-derived nitric oxide, which exerts a primary vasodilator stimulus on vascular myocytes, via cytoplasmic cyclic GMP. Here, we investigated whether the cGMP-degrading enzyme phosphodiesterase-5 (PDE5) is present in small penetrating arteries in the deep subcortical white matter of older people...
December 26, 2018: Journal of Neuropathology and Experimental Neurology
Paul J Lee, Chloë A Kerridge, Debotri Chatterjee, Arnulf H Koeppen, Phyllis L Faust, Elan D Louis
The underlying biology of essential tremor (ET) is poorly understood. Purkinje cell (PC) loss has been observed in some studies, although this finding remains somewhat controversial. Basket cells are interneurons whose axonal collaterals form a plexus around PC soma. When there is PC loss, this basket plexus appears empty. We used dual immunohistochemical staining for calbindin D28k and glutamic acid decarboxylase to quantify "empty baskets" as an indirect and alternative method of detecting PC loss...
December 26, 2018: Journal of Neuropathology and Experimental Neurology
Janice S Ahn, William Harrison, Elin Hughes, Roger E McLendon
Rare pilocytic astrocytomas (PA) have been described to arise in the ventricles of children. They are even less common in this location for the adult population. We present the case of a 44-year old man presenting with vision and mental status changes. Brain imaging revealed an intraventricular mass within the right ventricular atrium, most consistent with a meningioma. Microscopic examination revealed a neoplasm composed of elongated to plump bipolar astrocytes arranged in a fascicular architecture, accompanied by foci containing numerous Rosenthal fibers...
December 17, 2018: Journal of Neuropathology and Experimental Neurology
Elena V Daoud, Megan Wachsmann, Timothy E Richardson, Divya Mella, Edward Pan, Anna Schwarzbach, Dwight Oliver, Kimmo J Hatanpaa
Pleomorphic xanthoastrocytoma (PXA) is a slow-growing neoplasm that predominantly affects the pediatric and young adult population. This neoplasm has a good prognosis, with a median 10-year survival rate of 70%. The majority of tumors are supratentorial and arise in the temporal lobe, while spinal tumors are extremely rare, with only 8 reported cases. Molecular perturbations involving the MAPK/ERK signaling pathway have been described in PXAs. The most common mutation is BRAF V600E in 60%-80% of cases. Other mechanisms activating this pathway in the absence of this mutation are rare and include CRAF (RAF1) fusion genes...
December 5, 2018: Journal of Neuropathology and Experimental Neurology
Eric S Lipp, Patrick Healy, Alan Austin, Alysha Clark, Tara Dalton, Kathryn Perkinson, James E Herndon, Henry S Friedman, Allan H Friedman, Darell D Bigner, Roger E McLendon
Glioma therapeutic resistance to alkylating chemotherapy is mediated via O6-methylguanine-DNA methyltransferase (MGMT). We hypothesized that a CD45/HAM56/MGMT double-stained cocktail would improve MGMT discrimination in tumor cells versus inflammatory and endothelial cells (IEC). Total MGMT protein was quantified by IHC on 982 glioblastomas (GBM) and 199 anaplastic astrocytomas. Correcting for IEC was done by a CD45/HAM56/MGMT 2-color cocktail. Lowest IEC infiltrates (IEC "cold spots") were identified to quantitate MGMT as well as the percentage of IEC% in the IEC cold spots...
November 30, 2018: Journal of Neuropathology and Experimental Neurology
Tatiana P Schnieder, Isaiah D Zhou Qin, Iskra Trencevska-Ivanovska, Gorazd Rosoklija, Aleksandar Stankov, Goran Pavlovski, J John Mann, Andrew J Dwork
Inflammatory processes may contribute to psychiatric disorders and suicide. Earlier, we reported greater densities of perivascular phagocytes in dorsal prefrontal white matter (DPFWM) in suicide than in non-suicide deaths. To distinguish between greater vascularity and greater coverage of vessels by perivascular phagocytes, and to determine whether the excess of perivascular phagocytes is derived from microglia or from non-parenchymal immune cells, we made stereological estimates of vascular surface area density (AVTOTAL) by staining for glucose transporter Glut-1, and the fraction of vascular surface area (AF) immunoreactive (IR) for CD163 (CD163 AF) in dorsal and ventral prefrontal white and gray matter...
November 28, 2018: Journal of Neuropathology and Experimental Neurology
Kuan-Hung Chen, Hao-Yi Hsiao, Christopher Glenn Wallace, Kun-Chen Lin, Yi-Chen Li, Tien-Hung Huang, Chi-Ruei Huang, Yi-Ling Chen, Chi-Wen Luo, Fan-Yen Lee, Hon-Kan Yip
This study tested the hypothesis that combined adipose-derived mesenchymal stem cell (ADMSC) and low-energy extracorporeal shock wave (ECSW) therapy could protect brain from brain death (BD)-induced injury. Adult male Sprague Dawley rats were categorized into group 1 (sham control), group 2 (BD), group 3 (BD + ECSW [0.15 mJ/mm2/300 impulses] applied to the skull surface 3 hours after BD induction), group 4 (BD + ADMSC [1.2 × 106 cell] by intravenous injection 3 hours after BD induction) and group 5 (BD + ECSW + ADMSC)...
November 26, 2018: Journal of Neuropathology and Experimental Neurology
Daniel Skuk, Jacques P Tremblay
We have previously studied in nonhuman primates several aspects of the acute rejection of myofibers, including the histological characteristics, the mechanisms of myofiber elimination by the T cells, and the development of anti-donor antibodies. Here, we report the participation of the complement membrane attack complex (MAC) in this context. We used muscle sections of macaques from experiments of allogeneic muscle precursor cell transplantation with confirmed rejection of the graft-derived myofibers. Sections were stained with hematoxylin and eosin, alizarin red and for immunodetection of MAC, CD8, CD4, C3, C4d, and immunoglobulins...
November 26, 2018: Journal of Neuropathology and Experimental Neurology
Kristina M Joyal, Jean Michaud, Marjo S van der Knaap, Marianna Bugiani, Sunita Venkateswaran
Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare hypomyelinating leukodystrophy characterized by infantile or childhood onset of motor developmental delay, progressive rigidity and spasticity, with hypomyelination and progressive atrophy of the basal ganglia and cerebellum due to a genetic mutation of the TUBB4A gene. It has only been recognized since 2002 and the full spectrum of the disorder is still being delineated. Here, we review a case report of a severely affected girl with a thorough neuropathological evaluation demonstrating novel clinical and pathological findings...
November 22, 2018: Journal of Neuropathology and Experimental Neurology
Rie Saito, Hiroaki Nozaki, Taisuke Kato, Yasuko Toyoshima, Hajime Tanaka, Yutaka Tsubata, Tetsuo Morioka, Yoh Horikawa, Kiyomitsu Oyanagi, Takashi Morita, Osamu Onodera, Akiyoshi Kakita
Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an autosomal-dominant disorder involving the cerebral, retinal, renal, and other systemic microvessels due to frameshift mutations in the TREX1 gene. Under physiological conditions, the TREX1 protein is localized in the cellular cytoplasm and perinuclear area, but translocates into the nucleus in response to oxidative DNA damage. It has been speculated that aberrant localization of the protein may be associated with systemic microangiopathy in patients with RVCL...
November 17, 2018: Journal of Neuropathology and Experimental Neurology
Riyad El-Khoury, Sahar Traboulsi, Tarek Hamad, Maher Lamaa, Raja Sawaya, Mamdouha Ahdab-Barmada
Limb girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive disorder characterized by progressive muscle weakness and wasting. LGMD2A is caused by mutations in the calpain-3 gene (CAPN3) that encodes a Ca2+-dependent cysteine protease predominantly expressed in the skeletal muscle. Underlying pathological mechanisms have not yet been fully elucidated. Mitochondrial abnormalities have been variably reported in human subjects with LGMD2A and were more systematically evaluated in CAPN3-knocked out mouse models...
November 15, 2018: Journal of Neuropathology and Experimental Neurology
Lisa M Mangus, Rachel L Weinberg, Audrey C Knight, Suzanne E Queen, Robert J Adams, Joseph L Mankowski
Human immunodeficiency virus-associated sensory neuropathy (HIV-SN) remains a frequent neurologic complication of HIV infection. Little is known about alterations in the peripheral nervous system during the early stages of HIV, a time when neuroprotective interventions may be most beneficial. We performed Nanostring gene expression analysis on lumbar dorsal root ganglia (DRG) from 6 simian immunodeficiency virus (SIV)-infected pigtailed macaques killed at 7 days post-inoculation and 8 uninfected controls. We found significant upregulation of many genes involved in immune signaling and activation in the DRG...
November 4, 2018: Journal of Neuropathology and Experimental Neurology
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January 1, 2019: Journal of Neuropathology and Experimental Neurology
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