Spontaneous early-onset neurodegeneration in the brainstem and spinal cord of NSG, NOG, and NXG mice.

The spectrum of background, incidental, and experimentally induced lesions affecting NSG and NOG mice has been the subject of intense investigation. However, comprehensive studies focusing on the spontaneous neuropathological changes of these immunocompromised strains are lacking. This work describes the development of spontaneous early-onset neurodegeneration affecting both juvenile and adult NSG, NOG, and NXG mice. The study cohort consisted of 367 NSG mice of both sexes (including 33 NSG-SGM3), 61 NOG females (including 31 NOG-EXL), and 4 NXG females. These animals were primarily used for preclinical CAR T-cell testing, generation of humanized immune system chimeras, and/or tumor xenograft transplantation. Histopathology of brain and spinal cord and immunohistochemistry (IHC) for AIF-1, GFAP, CD34, and CD45 were performed. Neurodegenerative changes were observed in 57.6% of the examined mice (affected mice age range was 6-36 weeks). The lesions were characterized by foci of vacuolation with neuronal degeneration/death and gliosis distributed throughout the brainstem and spinal cord. IHC confirmed the development of gliosis, overexpression of CD34, and a neuroinflammatory component comprised of CD45-positive monocyte-derived macrophages. Lesions were significantly more frequent and severe in NOG mice. NSG males were considerably more affected than NSG females. Increased lesion frequency and severity in older animals were also identified. These findings suggest that NSG, NOG, and NXG mice are predisposed to the early development of identical neurodegenerative changes. While the cause of these lesions is currently unclear, potential associations with the genetic mutations shared by NSG, NOG, and NXG mice as well as unidentified viral infections are considered.

Clinically Manifesting, Naturally Occurring Fowl Glioma in a Leghorn Chicken in Germany.

Fowl glioma-inducing virus (FGV), a strain of avian leukosis virus (ALV) subgroup A, is the causal agent of fowl glioma characterized by multiple nodular astrocytic growths, gliosis, and lymphocytic encephalitis. Also associated with FGV infection are cases of cerebellar hypoplasia, perineuromas, and nonsuppurative myocarditis. Though fowl glioma has been recognized in several countries, most reports of FGV infection come from Japan. A 9-mo-old brown leghorn from a German farm with nine leghorns was presented to a veterinarian with an impaired general health with torticollis, tremor, and incoordination. Histopathology revealed multifocal nodular astrocytic growths, gliosis, and a lymphoplasmacytic encephalitis. Immunohistochemically, neoplastic astrocytes showed positivity for anti-ALV antibody. FGV was detected in the brain with nested reverse transcription-polymerase chain reaction (RT-PCR) and subsequent sequencing of PCR product. The remaining eight birds were screened for the presence of ALV with real-time RT-PCR. Four leghorns tested positive for exogenous ALV in nested RT-PCR with an identical nucleotide sequence as the leghorn with neurological symptoms. To the authors' knowledge this is the first report of a natural FGV infection in a brown leghorn in Germany with clinical manifestation.

Glioma aviar de manifestación clínica y natural en un pollo Leghorn en Alemania. El virus inductor del glioma del pollo (FGV), una cepa del subgrupo A del virus de la leucosis aviar (ALV), es el agente causal del glioma del pollo caracterizado por crecimientos astrocíticos nodulares múltiples, gliosis y encefalitis linfocítica. También se asocian con la infección por este virus, casos de hipoplasia cerebelar, perineuromas y miocarditis no supurativa. Aunque el glioma aviar se ha reconocido en varios países, la mayoría de los informes de infección por el virus inductor del glioma del pollo provienen de Japón. Un pollo Leghorn marrón de nueve meses de edad proveniente de una granja alemana con nueve aves Leghorns fue remitido a una clínica veterinaria con problemas de salud en general, tortícolis, temblores y falta de coordinación. La histopatología reveló crecimientos astrocíticos nodulares multifocales, gliosis y encefalitis linfoplasmocítica. Inmunohistoquímicamente, los astrocitos neoplásicos mostraron reacción positiva para anticuerpos contra el virus de la leucosis aviar. El virus inductor del glioma del pollo se detectó en el cerebro mediante transcripción reversa y reacción en cadena de la polimerasa anidada (RT-PCR) y con secuenciación posterior del producto de PCR. Las ocho aves restantes se examinaron para detectar la presencia del virus de la leucosis aviar mediante RT-PCR en tiempo real. Cuatro aves Leghorn dieron positivo para virus exógenos de leucosis mediante RT-PCR anidada y con una secuencia de nucleótidos idéntica a la del ave Leghorn con síntomas neurológicos. De acuerdo con el conocimiento de los autores, este es el primer informe de una infección natural por el virus inductor del glioma del pollo en un ave Leghorn marrón en Alemania que presentaba manifestaciones clínicas.

Myelopathy and Reactive Microgliosis and Astrogliosis in Equine Back Pain.

Equine chronic back pain (CBP) has been linked to different pathologic processes, which directly or indirectly involve spinal structures. Thus, making diagnosis and management very challenging with most horses with the condition recommended for early retirement from athletic activity. This study described the spinal cord lesions and the development of reactive microgliosis and astrocytosis in the spinal cords of horse with CBP. Thoracolumbar spinal cord segments from three horses euthanized because of unresolved CBP were dissected and grossly and histopathologically examined. The expression of activated microglia and astrocytes were demonstrated immunohistochemically using polyclonal rabbit anti-Iba-1 and anti-glial fibrillary acidic protein antibodies, respectively. All horses had radiological evidence of varying degrees of kissing spine involving six to nine vertebrae with the majority of the lesions graded between 2 and 5. Grossly, there was myelomalacia with intramedullary hemorrhages. The gray matters of the spinal cords were characterized by hemorrhagic malacic lesions with medullary disintegration. Reactive microgliosis and astrocytosis were evident in the spinal dorsal horns. White matter lesions include axonal swollen and/or loss, satellitosis, and varying degrees of dilation of myelin sheaths with some containing macrophages. In conclusion, the presence of reactive microgliosis and astrogliosis in the spinal dorsal horn indicates that they are possible precipitating factors in the development of equine CBP.

Feline Infectious Peritonitis: Immunohistochemical Features of Ocular Inflammation and the Distribution of Viral Antigens in Structures of the Eye.

Feline infectious peritonitis (FIP) is a serious, widely distributed systemic disease caused by feline coronavirus (FCoV), in which ocular disease is common. However, questions remain about the patterns of ocular inflammation and the distribution of viral antigen in the eyes of cats with FIP. This study characterized the ocular lesions of FIP including the expression of glial fibrillary acidic protein and proliferating cell nuclear antigen by Müller cells in the retina in cases of FIP and to what extent macrophages are involved in ocular inflammation in FIP. Immunohistochemistry for FCoV, CD3, CD79a, glial fibrillary acidic protein, calprotectin, and proliferating cell nuclear antigen was performed on paraffin sections from 15 naturally occurring cases of FIP and from controls. Glial fibrillary acidic protein expression was increased in the retina in cases of FIP. Müller cell proliferation was present within lesions of retinal detachment. Macrophages were present in FIP-associated ocular lesions, but they were the most numerous inflammatory cells only within granulomas (2/15 cats, 13%). In cases of severe inflammation of the ciliary body with damage to blood vessel walls and ciliary epithelium (3/15, 20%), some macrophages expressed FCoV antigens, and immunolabeling for calprotectin on consecutive sections suggested that these FCoV-positive macrophages were likely to be recently derived from blood. In cases of severe and massive inflammation of most ocular structures (4/15, 26%), B cells and plasma cells predominated over T cells and macrophages. These results indicate that gliosis can be present in FIP-affected retinas and suggest that breakdown of the blood-ocular barrier can allow FCoV-bearing macrophages to access the eye.

Glial scar-modulation as therapeutic tool in spinal cord injury in animal models

Abstract Purpose: Spinal Cord injury represents, in veterinary medicine, most of the neurological attendances and may result in permanent disability, death or euthanasia. Due to inflammation resulting from trauma, it originates the glial scar, which is a cell interaction complex system. Its function is to preserve the healthy circuits, however, it creates a physical and molecular barrier that prevents cell migration and restricts the neuroregeneration ability. Methods: This review aims to present innovations in the scene of treatment of spinal cord injury, approaching cell therapy, administration of enzyme, anti-inflammatory, and other active principles capable of modulating the inflammatory response, resulting in glial scar reduction and subsequent functional improvement of animals. Results: Some innovative therapies as cell therapy, administration of enzymes, immunosuppressant or other drugs cause the modulation of inflammatory response proved to be a promising tool for the reduction of gliosis. Conclusion: Those tools promise to reduce gliosis and promote locomotor recovery in animals with spinal cord injury.

Atypical nodular astrocytosis in simian immunodeficiency virus-infected rhesus macaques (Macaca mulatta).

BACKGROUND: Simian immunodeficiency virus (SIV), a model for HIV pathogenesis, is associated with neuropathology. METHODS: Five SIV-infected animals were selected following a database search of 1206 SIV-infected animals for nodular or astrocytic lesions. Two of five had neurologic dysfunction, and 3 of 5 were incidental findings. RESULTS: Histologic examination revealed multifocal nodular foci in the gray and white matter formed by interlacing astrocytes with abundant cytoplasm and large, reactive nuclei. Nodules were often enmeshed with small capillaries. Immunohistochemistry revealed variable immunoreactivity for a panel of markers: GFAP (4/5), vimentin (5/5), Glut-1 (1/5), CNPase (0/5), S100 (5/5), Iba1 (0/5), Ki67 (0/5), and p53 (4/4). In situ hybridization failed to detect any SIV RNA (0/5). Immunohistochemistry for simian virus 40, rhesus cytomegalovirus, and rhesus lymphocryptovirus failed to detect any antigen within the lesions. CONCLUSION: The immunoreactivity of p53 in the lesions compared with adjacent tissue suggests a local derangement in astrocyte proliferation and function.

Bilateral hippocampal malformation and concurrent granulomatous meningoencephalitis in a dog with refractory epilepsy.

A 5-year-old dog was referred with a history of anorexia and apathy for 3 weeks and acute status epilepticus. Ten weeks later the animal was humanely destroyed due to refractory epilepsy despite anti-epileptic medical treatment. Microscopical examination of the brain revealed bilateral malformation of the dentate gyrus with abnormal gyration. Cornu ammonis segments comprised of sparse pyramidal cells accompanied by marked gliosis. Additionally, there was severe generalized disseminated granulomatous meningoencephalitis, mainly localized to the white matter of the cerebral hemispheres. This is the first description of bilateral hippocampal malformation in a dog.

A canine case of gliosis with cyst formation in the posterior fossa.

A 5-month-old male Great Pyrenees with symptoms of convulsions, circling, and a head tilt was referred to the Animal Medical Center of Nihon University. On a magnetic resonance image (MRI), a cyst in the posterior fossa was noted and a part of the cyst enhanced by gadoteridol. Based on MRI and clinical findings, the patient was tentatively diagnosed with a cyst formation tumor, and an operation to open the cyst and remove the part enhanced by contrast was performed. Postoperatively, the clinical course was good. Pathologically, the removed tissue was diagnosed as a gliosis with cyst formation.

Naturally-occurring Neospora caninum infection in an adult sheep and her twin fetuses.

Neospora caninum tissue cysts were found in the brains of surgically delivered twin fetuses at 119 days of gestation. In the brains of both fetuses, there was an inflammatory reaction involving perivascular cuffings of mononuclear cells, glial nodules. The dam of these fetuses died because of metritis. Histopathological examination of the ewe revealed N. caninum tissue cysts and focal gliosis with mononuclear cell cuffings. A N. caninum-specific DNA fragment was detected in a brain homogenate of the ewe by the polymerase chain reaction method. This is the first report of N. caninum infection in twin ovine fetuses and in an adult sheep.

Reversible magnetic resonance imaging abnormalities in dogs following seizures.

Reversible magnetic resonance (MR) imaging lesions have been described in humans following seizures. This condition has not yet been reported in animals. This paper describes reversible abnormalities identified in 3 dogs using MR imaging that was performed initially within 14 days of the last seizure and follow-up imaging that was performed after 10 to 16 weeks of anticonvulsant therapy. All three dogs had lesions in the piriform/temporal lobes, characterized by varying degrees of hyperintensity on T2-weighted images and hypointensity on T1-weighted images. In one dog, contrast enhancement was evident. On reevaluation, partial resolution occurred in all 3 dogs. In a fourth animal with an olfactory meningioma, similar appearing lesions in the temporal cortex and right and left piriform lobes were identified after seizure activity. A surgical biopsy of the temporal cortex and hippocampus was performed and edema, neovascularization, reactive astrocytosis, and acute neuronal necrosis were evident. These histologic findings are similar to those reported in humans with seizures. Recognizing the potential occurrence of reversible abnormalities in MR images is important in developing a diagnostic and therapeutic plan in canine patients with seizures. Repeat imaging after seizure control may help differentiate between seizure-induced changes and primary multifocal parenchymal abnormalities.