Liquefactive necrosis of the brain

A 12-month-old American Miniature horse colt was presented to the Virginia Tech Veterinary Teaching Hospital with a 7-month history of progressive ataxia. Physical examination revealed a head intention tremor, base-wide stance, and ataxia. Necropsy findings were confined to the brain. There were bilateral areas of liquefactive necrosis and cavitation corresponding to the dorsal accessory olivary and lateral (accessory) cuneate nuclei. Cerebellar folia of the dorsal vermis were thin. Microscopically, the cerebellar cortex was characterized by patchy areas of Purkinje cell loss with associated variable thinning of the molecular and granule cell layers and astrogliosis. Dorsal accessory olivary and lateral cuneate nuclei were cavitated and had mild glial response around their periphery. Additionally, a focus of necrosis and neuropil vacuolization was found in the right putamen. These findings indicate the presence of a neurodegenerative disorder centered, but not confined to, the cerebellum and its connections in this American Miniature horse colt.

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Induced Neurocysticercosis in Rhesus Monkeys (Macaca mulatta) Produces Clinical Signs and Lesions Similar to Natural Disease in Man

The Scientific World JOURNAL ◽

10.1155/2014/248049 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

N. Chowdhury ◽

A. Saleque ◽

N. K. Sood ◽

L. D. Singla

Keyword(s):

Macaca Mulatta ◽

Rhesus Monkeys ◽

Clinical Signs ◽

Clinical Manifestations ◽

Epileptic Seizures ◽

Cognitive Responses ◽

Chronic Inflammatory Response ◽

Experimental Animal Models ◽

Liquefactive Necrosis ◽

The Brain

Neurocysticercosis is a serious endemic zoonosis resulting in increased cases of seizure and epilepsy in humans. The genesis of clinical manifestations of the disease through experimental animal models is poorly exploited. The monkeys may prove useful for the purpose due to their behavior and cognitive responses mimicking man. In this study, neurocysticercosis was induced in two rhesus monkeys each with 12,000 and 6,000 eggs, whereas three monkeys were given placebo. The monkeys given higher dose developed hyperexcitability, epileptic seizures, muscular tremors, digital cramps at 10 DPI, and finally paralysis of limbs, followed by death on 67 DPI, whereas the monkeys given lower dose showed delayed and milder clinical signs. On necropsy, all the infected monkeys showed numerous cysticerci in the brain. Histopathologically, heavily infected monkeys revealed liquefactive necrosis and formation of irregular cystic cavities lined by atrophied parenchymal septa with remnants of neuropil of the cerebrum. In contrast, the monkeys infected with lower dose showed formation of typical foreign body granulomas characterized by central liquefaction surrounded by chronic inflammatory response. It was concluded that the inflammatory and immune response exerted by the host against cysticerci, in turn, led to histopathological lesions and the resultant clinical signs thereof.

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Pathogenesis of Equid Alphaherpesvirus 1 Infection in the Central Nervous System of Mice

Veterinary Pathology ◽

10.1177/03009858211020670 ◽

2021 ◽

pp. 030098582110206

Author(s):

Leonardo P. Mesquita ◽

Rafael C. Costa ◽

Laís L. R. Mesquita ◽

Maria do Carmo C. S. H. Lara ◽

Eliana M. C. Villalobos ◽

...

Keyword(s):

Caspase 3 ◽

Viral Infections ◽

Neuronal Degeneration ◽

Inflammatory Cells ◽

Post Inoculation ◽

Neurological Signs ◽

Liquefactive Necrosis ◽

The Central Nervous System ◽

The Brain ◽

Apoptosis Marker

Equid alphaherpesvirus 1 (EHV-1) causes myeloencephalopathy in horses and occasionally in non-equid species. Although mouse models have been developed to understand EHV-1 pathogenesis, few EHV-1 strains have been identified as highly neurovirulent to mice. The aim of this study was to evaluate the pathogenesis of 2 neurovirulent EHV-1 strains in mice, and to characterize the inflammatory cells and expression of chemokines and the apoptosis marker caspase-3 in the brain of infected mice. C57BL/6J mice were inoculated intranasally with EHV-1 strains A4/72 or A9/92 and evaluated on 1, 2, and 3 days post inoculation (DPI). EHV-1-infected mice showed severe neurological signs at 3 DPI. Ultrastructural analysis revealed numerous viral nucleocapsids and fewer enveloped virions within degenerated and necrotic neurons and in the surrounding neuropil. Histologically, at 3 DPI, there was severe diffuse neuronal degeneration and liquefactive necrosis, prominent microgliosis, and perivascular cuffing composed of CD3+ cells (T cells) and Iba-1+ cells (macrophages), mainly in the olfactory bulb and ventral portions of the brain. In these areas, moderate numbers of neuroglial cells expressed CCL5 and CCL2 chemokines. Numerous neurons, including those in less affected areas, were immunolabeled for cleaved caspase-3. In conclusion, neurovirulent EHV-1 strains induced a fulminant necrotizing lymphohistiocytic meningoencephalitis in mice, with microgliosis and expression of chemokines and caspase-3. This model will be useful for understanding the mechanisms underlying the extensive neuropathology induced by these viral infections.

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Liquefaction of the brain following stroke shares a similar molecular and morphological profile with atherosclerosis and mediates secondary neurodegeneration in an osteopontin dependent mechanism

10.1101/264275 ◽

2018 ◽

Cited By ~ 1

Author(s):

Amanda G. Chung ◽

Jennifer B. Frye ◽

Jacob C. Zbesko ◽

Eleni Constantopoulos ◽

Megan Hayes ◽

...

Keyword(s):

Inflammatory Response ◽

Brain Ischemia ◽

Molecular Profile ◽

Central Component ◽

Phagocytic Cells ◽

Cholesterol Crystals ◽

Neuronal Nuclei ◽

Myelin Debris ◽

Liquefactive Necrosis ◽

The Brain

AbstractHere we used mouse models of heart and brain ischemia to compare the inflammatory response to ischemia in the heart, a protein rich organ, to the inflammatory response to ischemia in the brain, a lipid rich organ. We report that ischemia-induced inflammation resolves between 1 and 4 weeks in the heart compared to between 8 and 24 weeks in the brain. Importantly, we discovered that a second burst of inflammation occurs in the brain between 4 and 8 weeks following ischemia, which coincided with the appearance of cholesterol crystals within the infarct. This second wave shares a similar cellular and molecular profile with atherosclerosis and is characterized by high levels of osteopontin (OPN) and matrix metalloproteinases (MMPs). In order to test the role of OPN in areas of liquefactive necrosis, OPN-/- mice were subjected to brain ischemia. We found that at 7 weeks following stroke, the expression of pro-inflammatory proteins and MMPs was profoundly reduced in the infarct of the OPN-/- mice, although the number of cholesterol crystals was increased. OPN-/- mice exhibited faster recovery of motor function and a higher number of neuronal nuclei (NeuN) positive cells in the peri-infarct area at 7 weeks following stroke. Based on these findings we propose that the brain liquefies after stroke because phagocytic cells in the infarct are unable to efficiently clear cholesterol rich myelin debris, and that this leads to the perpetuation of an OPN-dependent inflammatory response characterized by high levels of degradative enzymes.Significance StatementThe inflammatory response to ischemia in the brain is different to the response to ischemic injury in other organs. In the brain, and for unknown reasons, dead tissue liquefies in response to ischemia by the process of liquefactive necrosis. However, the data we present here demonstrate that there is overlap between the pathophysiology of liquefactive necrosis and atherosclerosis. Specifically, we show that chronic stroke infarcts contain foamy macrophages, cholesterol crystals, high levels of OPN and MMPs, and a similar cytokine profile to atherosclerosis. Therefore, because cholesterol is a central component of myelin, liquefactive necrosis in response to stroke may be caused by an inflammatory response to cholesterol-rich myelin debris that is driven in large part by OPN and MMPs.

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Continuous Intratumoral Infusion of Methotrexate for Recurrent Glioblastoma: A Pilot Study

Neurosurgery ◽

10.1227/00006123-199105000-00023 ◽

1991 ◽

Vol 28 (5) ◽

pp. 752-761 ◽

Cited By ~ 20

Author(s):

David Nierenberg ◽

Robert Harbaugh ◽

Herbert L. Maurer ◽

Teddi Reeder ◽

Gregory Scott ◽

...

Keyword(s):

Steady State ◽

Serum Levels ◽

Recurrent Glioblastoma ◽

Tumor Bed ◽

Methotrexate Concentration ◽

Liquefactive Necrosis ◽

Methotrexate Dose ◽

Steady State Levels ◽

Csf Levels ◽

The Brain

Abstract Five patients with documented recurrences of glioblastoma multiforme were given continuous infusions of methotrexate delivered intratumorally using implantable catheters and subcutaneous refillable pumps. A continuous infusion of methotrexate (1 mg/d) was begun with concomitant oral administration of folinic acid. The methotrexate dose was increased every 2 weeks to 3, 10, 30, and, ultimately, 75 mg/d in two patients. Samples of serum and ventricular cerebrospinal fluid (CSF) were obtained to determine the levels of methotrexate and total bioactive folates, and brain tissue was obtained from two patients for determination of methotrexate concentration. The patients survived from 7 to 49 weeks after the implantation of the infusion device. Neither the clinical examination nor sequential radiological studies gave clear evidence of reduction in tumor size. Pneumonia developed in one patient, and mild hepatitis and increased seizure frequency in another. Methotrexate was stable in the delivery system over 12 days, and ventricular CSF reached steady-state levels by 5 days. Steady-state ventricular CSF levels of methotrexate were higher than serum levels in some patients, while the reverse was true in others. Levels of total bioactive folates in the CSF did not increase above the normal range. Methotrexate concentrations were highest at the center of the tumor, but measurable amounts of methotrexate were detectable in all areas of the brain. At autopsy in four patients, variable liquefactive necrosis of the brain tumors was seen, and viable tumor was found at the periphery of the tumor bed. These preliminary results suggest that it is technically feasible to infuse methotrexate into brain tumor cavities, and show that little central nervous system or systemic toxicity was encountered in five patients. Better delineation of the safety and efficacy of this therapeutic approach will require further clinical trials.

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