Spinal Cord Medulloepithelioma in a Cat.

A 13-month-old, neutered, male, domestic shorthair cat was referred with a history of progressive paraparesis, proprioceptive ataxia, and lumbar spinal pain. Neurological examination revealed non-ambulatory paraparesis consistent with L4-S1 myelopathy. Magnetic resonance of the thoracolumbar spinal cord identified a dorsal intradural extramedullary space-occupying lesion extending from L5 to L6. It was homogeneously hyperintense in T2-weighted imaging and isointense in T1-weighted imaging and exhibited marked and homogeneous contrast enhancement in the T1-weighted post-contrast imaging. The removed tissue was composed of neoplastic cells arranged as pseudostratified or multilayered trabecular and tubular structures, supported by internal and external limiting PAS-positive membranes. The neoplastic cells were immunoreactive for vimentin and NSE and negative for GFAP, Olig2, synaptophysin, PCK, S-100, NeuN, and nestin. The Ki-67 nuclear labeling index was up to 90%. The tumor was consistent with the diagnosis of medulloepithelioma, which is most frequently reported as an intraocular tumor. The morphological and immunohistochemical features of the tumor showed remarkable concordance with most human medulloepitheliomas. This is the first spinal cord medullopethelioma report in a cat, with the clinical, neuroradiological, histological, and immunohistochemical findings being described.

Endometrial expression of antimicrobial peptides as markers of subclinical endometritis in mares.

BACKGROUND: Endometritis is a major cause of subfertility in mares. Multiparous old mares are more susceptible to developing endometritis given that ageing is associated with an altered immune response and with inadequate physiological uterine clearance after breeding, which can lead to degenerative changes in the endometrium. Molecules such as antimicrobial peptides (AMPs) have been proposed as endometritis markers in the equine species. STUDY DESIGN: Cross-sectional. OBJECTIVES: To investigate the endometrial expression of defensin-beta 4B (DEFB4B), lysozyme (LYZ) and secretory leukocyte peptidase inhibitor (SLPI) genes in mares either affected or not by subclinical endometritis, due to the role of these AMPs in the immune response to bacteria and inflammatory reactions. METHODS: Endometrial biopsy for histopathological and gene expression examinations was performed on 26 mares. The inclusion criteria for the normal mare group (NM, N = 7) were 2-4 years of age, maiden status, no clinical signs of endometritis and a uterine biopsy score of I, while for mares affected by subclinical endometritis (EM, N = 19) the inclusion criteria were 10-22 years of age, barren status for 1-3 years, no clinical signs of endometritis and a uterine biopsy score between IIA and III. RESULTS: A significantly higher expression of LYZ (NM: 0.76 [1.84-0.37] vs. EM: 2.78 [5.53-1.44], p = 0.0255) and DEFB4B (NM: 0.06 [0.11-0.01] vs. EM: 0.15 [0.99-0.08], p = 0.0457) genes was found in endometritis mares versus normal mares. Statistically significant moderate positive correlations were found between the level of expression of LYZ gene and both the age (r = 0.4071, p = 0.039) and the biopsy grade (r = 0.4831, p = 0.0124) of the mares. MAIN LIMITATIONS: The study investigated a limited number of genes and mares, and the presence/location of the proteins coded by these genes was not confirmed within the endometrium by IHC. CONCLUSIONS: If the results of this study are confirmed, LYZ and DEFB4B genes can be used as markers to identify mares that are affected by subclinical endometritis.

Evaluation of species-specific polyclonal antibodies to detect and differentiate between Neospora caninum and Toxoplasma gondii.

Neosporosis and toxoplasmosis are major causes of abortion in livestock worldwide, leading to substantial economic losses. Detection tools are fundamental to the diagnosis and management of those diseases. Current immunohistochemistry (IHC) tests, using sera raised against whole parasite lysates, have not been able to distinguish between Toxoplasma gondii and Neospora caninum. We used T. gondii and N. caninum recombinant proteins, expressed in Escherichia coli and purified using insoluble conditions, to produce specific polyclonal rabbit antisera. We aimed to develop species-specific sera that could be used in IHC on formalin-fixed, paraffin-embedded (FFPE) tissue sections to improve the diagnosis of ruminant abortions caused by protozoa. Two polyclonal rabbit sera, raised against recombinant proteins, anti-Neospora-rNcSRS2 and anti-Toxoplasma-rTgSRS2, had specificity for the parasite they were raised against. We tested the specificity for each polyclonal serum using FFPE tissue sections known to be infected with T. gondii and N. caninum. The anti-Neospora-rNcSRS2 serum labeled specifically only N. caninum-infected tissue blocks, and the anti-Toxoplasma-rTgSRS2 serum was specific to only T. gondii-infected tissues. Moreover, tissues from 52 cattle and 19 sheep previously diagnosed by lesion profiles were tested using IHC with our polyclonal sera and PCR. The overall agreement between IHC and PCR was 90.1% for both polyclonal anti-rNcSRS2 and anti-rTgSRS2 sera. The polyclonal antisera were specific and allowed visual confirmation of protozoan parasites by IHC, but they were not as sensitive as PCR testing.

Detection of Leptomeningeal Carcinomatosis by Cerebrospinal Fluid in a Dog with a Negative MRI.

An 11 yr old female French bulldog was presented for acute onset of seizures and a 2 wk history of disorientation. On physical examination, a nodular mass at the fourth mammary gland level was observed. Neurological evaluation showed obtundation and compulsive behavior. Brain MRI study did not reveal any abnormalities. Cerebrospinal fluid (CSF) collected from the cerebellomedullary cistern showed a marked increase of total nucleated cell count (400 cells/µL). Cytological evaluation identified the presence of a monomorphic round cell population characterized by large cell bodies, a single eccentrical located nucleus with high nuclear:cytoplasmatic ratio, and marked atypia with anisocytosis, anisokaryosis, and multiple nucleoli. Leptomeningeal carcinomatosis (LC) was suspected. The dog was euthanatized for worsening of clinical signs. Post-mortem examination identified an anaplastic mammary carcinoma in the nodular mammary mass. Infiltration by neoplastic cells exhibiting the same morphological features was detected along leptomeninges of the telencephalon and cerebellum associated with cortical and subcortical parenchymal micrometastases. To our knowledge, this is the first case of LC in a dog detected by CSF evaluation but without any MRI abnormalities. This finding emphasizes the usefulness of CSF cytology in patients with suspected LC even in the absence of any MRI identifiable lesions.

A case of spermatic cord B-cell lymphoma relapsing to the brain in a dog.

A 13-year-old, intact male mixed-breed dog was referred to our clinic for lethargy and asthenia following an episode of gastroenteritis. As an incidental finding during abdominal ultrasound, a mass on the right spermatic cord was seen. Cytology of the mass revealed a monomorphic population of large, round cells with a lymphoid appearance. A bilateral orchiectomy was conducted, and histopathology revealed the presence of a B-cell lymphoma in the right spermatic cord. Based on clinical staging, which showed no involvement of other sites, no additional treatment was administered. Recheck evaluations were scheduled for every 3 mo thereafter. Five months after surgery, the dog developed left central vestibular syndrome with a paradoxical right-sided head tilt. An MRI of the brain showed multifocal lesions and, due to a rapidly worsening clinical condition, the dog was humanely euthanized. The histopathology of the brain lesions was consistent with B-cell lymphoma. Key clinical message: This is the first report of a primary spermatic cord lymphoma relapsing to the brain in a dog. Although rare, spermatic cord tumors should be included among the differential diagnoses for masses arising from the spermatic cord. If lymphoma is diagnosed, location to other sites, especially to the central nervous system, should be considered.

Un cas de lymphome à cellules B du cordon spermatique récidivant au cerveau chez un chien. Un chien de race mixte mâle intact de 13 ans a été référé à notre clinique pour léthargie et asthénie à la suite d'un épisode de gastro-entérite. Comme découverte fortuite lors d'une échographie abdominale, une masse sur le cordon spermatique droit a été observée. La cytologie de la masse a révélé une population monomorphe de grosses cellules rondes d'aspect lymphoïde. Une orchidectomie bilatérale a été réalisée et l'histopathologie a révélé la présence d'un lymphome à cellules B dans le cordon spermatique droit. Sur la base du stade clinique, qui n'a montré aucune implication d'autres sites, aucun traitement supplémentaire n'a été administré. Des évaluations de contrôle étaient programmées tous les 3 mois par la suite. Cinq mois après la chirurgie, le chien a développé un syndrome vestibulaire central gauche avec une inclinaison paradoxale de la tête du côté droit. Une IRM du cerveau a montré des lésions multifocales et, en raison d'une détérioration rapide de l'état clinique, le chien a été euthanasié sans cruauté. L'histopathologie des lésions cérébrales correspondait à un lymphome à cellules B.Message clinique clé :Il s'agit du premier rapport d'un lymphome primaire du cordon spermatique récidivant au cerveau chez un chien. Bien que rares, les tumeurs du cordon spermatique doivent être incluses dans les diagnostics différentiels des masses provenant du cordon spermatique. Si un lymphome est diagnostiqué, la localisation vers d'autres sites, en particulier vers le système nerveux central, doit être envisagée.(Traduit par Dr Serge Messier).

Feline Parvovirus Lethal Outbreak in a Group of Adult Cohabiting Domestic Cats.

Feline panleukopenia is a highly contagious and often fatal disease in cats. The virus, known as feline panleukopenia virus (FPV), primarily affects kittens and unvaccinated cats. It is transmitted through contact with infected cats or their bodily fluids, as well as contaminated objects and environments. The diagnosis of FPV infection can be confirmed through a combination of clinical signs, blood tests, and fecal testing. Prevention through vaccination is recommended for all cats. This case report describes an outbreak of feline panleukopenia in a group of unvaccinated domestic cats that resulted in acute mortality. The lesions were evaluated using histopathology, and the specific viral strain was characterized using molecular techniques. The clinical course of the outbreak was peracute, with a hemorrhagic pattern and 100% of lethality. The observed clinical-pathological pattern was unusual; nevertheless, molecular studies did not highlight peculiar genomic features of the parvovirus isolate. The outbreak affected 3 out of 12 cats in a very short time. However, the prompt application of biosecurity measures and vaccination resulted in an effective interruption of virus spread. In conclusion, we could assume that the virus found the ideal conditions to infect and replicate at high titers, resulting in a particularly aggressive outbreak.

Neuropathology of Central and Peripheral Nervous System Lymphoma in Dogs and Cats: A Study of 92 Cases and Review of the Literature.

The literature about nervous system lymphoma (NSL) in dogs and cats is fragmentary, based on a few case series and case reports with heterogeneous results. The aim of our study was to retrospectively analyze 45 cases of canine and 47 cases of feline NSL and compare our results with previously reported data, also providing an extensive literature review. Breed, age, gender, clinical signs, type, and neurolocalization were recorded for each case. The pathological patterns and phenotype were assessed by histopathology and immunohistochemistry. The occurrence of central and peripheral NSL was similar between the two species in both primary and secondary types. NSL occurred with a slightly higher prevalence in Labrador Retrievers, and spinal cord lymphoma (SCL) was associated with young age in cats. The most frequent locations were the forebrain in dogs and the thoracolumbar segment in cats. Primary central nervous system lymphoma (CNSL) in cats most frequently involved the forebrain meninges, particularly as a B-cell phenotype. Peripheral NSL mostly affected the sciatic nerve in dogs and had no preferred location in cats. Nine different pathological patterns were identified, with extradural as the most prevalent SCL pattern in both species. Finally, lymphomatosis cerebri was described for the first time in a dog.

Clinical features of muscle stiffness in 37 dogs with concurrent naturally occurring hypercortisolism.

BACKGROUND: Severe muscle stiffness (SMS) in dogs with hypercortisolism (HC) is uncommon. OBJECTIVES: To evaluate signalment, presentation, treatments, and long-term outcomes of dogs with concurrent HC and SMS. ANIMALS: Thirty-seven dogs. METHODS: Medical records of dogs with HC and concurrent SMS were recruited from 10 institutions. Clinical information, test results, therapeutic responses, and survival times were reviewed. RESULTS: All 37 dogs with HC and SMS had pituitary-dependent hypercortisolism (PDH); 36/37 weighed <20 kg. Signs and test results were typical of PDH aside from SMS, initially diagnosed in all 4 limbs in 9, pelvic limbs of 22, and thoracic limbs of 6 dogs. Hypercortisolism and SMS were diagnosed together in 3 dogs; HC 1-36 months before SMS in 23; SMS 1-12 months before HC in 11. Mitotane or trilostane, given to control HC in 36/37 dogs, improved or resolved HC signs in 28; SMS did not resolve, remaining static or worsening in 31/36 dogs, mildly improving in 5/19 dogs given additional therapies. Progression of SMS included additional limbs in 10 dogs and the masticatory muscles of 2. The median survival time from diagnosis of SMS was 965 days (range, 8-1188). CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent SMS and HC is uncommon, possibly affecting only dogs with PDH. Development of SMS might occur before or after diagnosis of HC. Apart from SMS, the clinical picture and survival time of these dogs seem indistinguishable from those of dogs with HC in general. However, while muscle weakness usually resolves with HC treatment SMS does not.

Loss of H3K27me3 expression in canine nerve sheath tumors.

Nerve sheath tumors (NSTs) are characterized by neoplastic proliferation of Schwann cells, perineurial cells, endoneurial and/or epineurial fibroblasts. Diagnosis of NST is often challenging, particularly in distinguishing malignant NST (MNST) from other soft tissue sarcomas, or sometimes between low-grade MNST and benign NST. Recent studies in human pathology have demonstrated loss of trimethylation at lysine 27 of histone 3 (H3K27me3) in a subset of MNSTs using immunohistochemistry. Loss of H3K27me3 expression is rare in other high-grade sarcomas and also appears to be useful in distinguishing benign and low-grade MNSTs from high-grade subsets. In our retrospective study, we performed H3K27me3 immunohistochemistry in 68 canine tumors previously diagnosed as NST. We detected loss of H3K27me3 expression in 25% (n = 17) of all canine NST, including one neurofibroma, whereas 49% (n = 33) of tumors had mosaic loss of expression and 26% (n = 18) retained expression. No statistically significant differences were found between H3K27me3 expression, histopathological features of tumors, and their immunoreactivity for Sox10, claudin-1, GFAP, and Ki67. Because the classification of canine NST is not yet fully established and its correlation with the prognosis and clinical course of the disease is lacking, prospective studies with possible genetic analyses are needed to assess the true diagnostic value of H3K27me3 loss in canine NST.

Comparative and quantitative morphology of the pig and wild boar cerebellum for identifying possible effects of domestication.

The domestic pig (Sus scrofa domesticus) stems from the Eurasian wild boar (Sus scrofa): this offers an appealing window to study microanatomical changes related to the process of domestication, the symbiotic relationship between human and animal. In this light, we quantitatively demonstrated significant microanatomical differences between pig and wild boar cerebella. Calbindin D-28, a calcium binding protein, was employed as immunohistochemical marker of the Purkinje cells. Our results showed that: (i) the foliation index, expressing the rate of cerebellar cortical folding, and the number of granular cells were not significantly different between pigs and wild boars; (ii) area of the granular layer and the molecular layer, and area of white matter were lower in pigs; (iii) the fraction area, grey matter/white matter, was higher in pigs; (iv) the Purkinje cell linear density and their soma area were higher in wild boars. Despite the morphological data alone are not sufficient to draw any final conclusions, our findings on Purkinje cells may represent good indicators of a reduction of the pig cerebellum motor and cognitive functions during the process wild boar-to-pig domestication.

Histopathological and Immunohistochemical Evaluation of Canine Nerve Sheath Tumors and Proposal for an Updated Classification.

Nerve sheath tumors are a group of tumors originating from Schwann cells, fibroblasts, and perineurial cells. In veterinary pathology, the terminology for nerve sheath tumors remains inconsistent, and many pathologists follow the human classification of such tumors in practice. Immunohistochemistry plays an important role in the diagnosis of nerve sheath tumors, but specific immunohistochemical and molecular biomarkers are lacking. In our study, we histopathologically reevaluated 79 canine nerve sheath tumors and assessed their reactivity for the immunohistochemical markers Sox10, claudin-1, GFAP, CNPase, and Ki-67. Based on the results, we classified the tumors according to the most recent human classification. Twelve cases were diagnosed as benign nerve sheath tumors, including six neurofibromas, three nerve sheath myxomas, two hybrid nerve sheath tumors (perineurioma/neurofibroma and perineurioma/schwannoma), and one schwannoma. Sixty-seven tumors were malignant nerve sheath tumors, including fifty-six conventional, four perineural, one epithelioid malignant nerve sheath tumor, and six malignant nerve sheath tumors with divergent differentiation. We believe that with the application of the proposed panel, an updated classification of canine nerve sheath tumors could largely follow the recent human WHO classification of tumors of the cranial and paraspinal nerves, but prospective studies would be needed to assess its prognostic value.

Malformation of the Cortical Development Associated with Severe Clusters of Epileptic Seizures.

Three cases of the malformation of the cortical development are described: a mixed breed dog and a Border Collie pup with a focal and diffuse cortical dysplasia, respectively, and a kitten with lissencephaly. All cases presented with intractable epilepsy and were euthanized, due to the cluster of epileptic seizures. The gross examination at necropsy revealed the morphologic alteration of the telencephalic region in two cases. Histopathologically, a disorganization of the cortical lamination with the presence of megalic neurons, was found in the focal cortical dysplasia case. An altered organization of the white and gray matter, with a loss of the normal neuronal distribution and altered neurons, characterized the diffuse cortical dysplasia case. In the lissencephalic cat, there was no recognizable organization of the brain with areas of neuroglial tissue forming nodules in the leptomeningeal space. We strongly support the hypothesis that, as in humans, as well as in the veterinary patients, malformations of the cortical development could be the cause of refractory epilepsy.

Degenerative Myelopathy in Hovawart Dogs: Molecular Characterization, Pathological Features and Accumulation of Mutant Superoxide Dismutase 1 Protein.

Degenerative myelopathy (DM) is an adult-onset, progressive neurological disease affecting several breeds of dog. Homozygosity or compound heterozygosity for the canine superoxide dismutase 1 (SOD1) gene mutations, possibly modulated by the modifier SP110 locus, are associated with a high risk for DM. Although the pathophysiological mechanisms are largely unknown, a role for mutant SOD1 in causing neuronal degeneration has been postulated. Three Hovawart dogs, 9-12 years of age, developed slowly progressive incoordination and weakness of the pelvic limbs leading to non-ambulatory flaccid paraparesis and muscle atrophy. Neuropathological lesions comprised axonal degeneration and loss of ascending and descending spinal pathways, which were most severe in the mid- to caudal thoracic segments. Accumulation of mutant SOD1 protein in neurons and reactive astrocytes was demonstrated by immunolabelling with the 16G9 antibody against the mutant SOD1 protein (p.E40K amino acid substitution). All three dogs were homozygous for the c.118A allele, but none had the SP110 'risk' haplotype, suggesting a weak association of SP110 with the onset of DM in this breed. Our data suggest that the Hovawart breed is predisposed to the SOD1:c.118G>A mutation, which is associated with the development of DM. Prevention of DM could be achieved with the help of strategies based on epidemiological and genetic testing.

Presence of pathogenic Leptospira spp. in the reproductive system and fetuses of wild boars (Sus scrofa) in Italy.

Leptospirosis is a re-emerging and globally spread zoonosis caused by pathogenic genomospecies of Leptospira. Wild boar (Sus scrofa) are an important Leptospira host and are increasing in population all over Europe. The aim of this investigation was to evaluate Leptospira spp. infection in the reproductive systems of wild boar hunted in two Italian regions: Tuscany and Sardinia. From 231 animals, reproductive system tissue samples (testicles, epididymides, uteri) as well as placentas and fetuses were collected. Bacteriological examination and Real-Time PCR were performed to detect pathogenic Leptospira (lipL32 gene). Leptospires were isolated from the testicles and epididymides of one adult and two subadult wild boar. Four isolates from the two subadult males were identified as Leptospira interrogans serogroup Australis by MLST, whereas Leptospira kirschneri serogroup Grippotyphosa was identified from the adult testicles and epididymis. Using Real-Time PCR, 70 samples were positive: 22 testicles (23.16%) and 22 epididymides (23.16%), 10 uteri (7.35%), 3 placentas (6.66%), and 13 fetuses (28.88%). Amplification of the rrs2 gene identified L. interrogans and L. kirschneri species. The results from this investigation confirmed that wild boar represent a potential source of pathogenic Leptospira spp. Isolation of Leptospira serogroups Australis and Grippotyphosa from the male reproductive system and the positive Real-Time PCR results from both male and female samples could suggest venereal transmission, as already demonstrated in pigs. Furthermore, placentas and fetuses were positive for the lipL32 target, and this finding may be related to a possible vertical transmission of pathogenic Leptospira.

Case Report: Use of Amniotic Microvesicles for Regenerative Medicine Treatment of a Mare With Chronic Endometritis.

Chronic endometritis is an inflammation in the inner layer of uterine mucosa, with or without an infectious process, which affects the animal's fertility but not its general health. A variety of treatments has been adopted over the years but to date, no effective cures have been able to renew the injured tissue. Since the defects in the fetal-maternal communication are caused by degenerative changes due to chronic endometrial inflammation, our working hypothesis was a new approach to this disease by the regenerative medicine using amniotic derived microvesicles (MVs) for their anti-inflammatory and regenerative effects. The MVs are responsible for horizontal transfer of genetic materials, including microRNA (miRNAs) that are involved in paracrine communication between origin cells and target cells. Thus, intrauterine MV infusion may be beneficial in degenerative chronic endometritis and in the fetal-maternal talk. The selected mare was an 11-year-old Friesian, with a history of failed pregnancies despite numerous insemination attempts. Punctual and evident heats characterized the reproductive history, but no insemination attempts had been made for many years. The first (failed) insemination was when the mare was 9-years-old. In the next two reproductive seasons, other attempts were made at regular intervals but none was successful. After a final insemination attempt using a stallion of proven fertility, the collection of an 8-day old embryo suggested that the mare was affected by implantation failure related to endometritis. The mare was treated with two cycles of intrauterine administration of amniotic-derived MVs. The success of the intrauterine administration of MVs was demonstrated by an improvement in the classification of endometritis and in a successful artificial insemination (AI) with implantation of an embryo, as detected at day 14 and with a pregnancy that is still ongoing. Probably, MVs were able to restore the injured endometrium and re-establish the proper communication for a successful embryo implantation.

Spinal Muscular Atrophy in Blonde D'Aquitaine Calves Is Not Associated With FVT1 Gene Mutation.

Spinal muscular atrophy (SMA) is a motor neuron disease (MND) in humans and diverse animal species: canid, felid, and bovid. To date, bovine SMA has been reported in Brown Swiss, Holstein, Friesian, and Red Danish breed; it has been associated with a genetic mutation of the FVT1 gene, also known as 3-ketodihydrosphingosine reductase (KDSR). The aim of the present case series was to describe clinical presentation, pathological findings, and genetic analysis of five Blond d'Aquitaine calves diagnosed with SMA and to determine whether the mutation was associated with the disease. Five Blonde d'Aquitaine calves (three females and two males) from the same cow-calf operation farm were presented between June 2018 and February 2019 because unable to stand or walk unassisted since birth. Neurological examination aroused suspicion of a diffuse lesion affecting the peripheral nervous system in all calves. Findings from electromyographic investigations and muscle and nerve biopsies were consistent with a non-regenerative, chronic, active axonal neuropathy and marked neurogenic muscular atrophy and assumed to be associated with a neurodegenerative process. Histopathological examination of tissue samples from two animals revealed neuronal loss and several degenerated, shrunken, and hypereosinophilic neurons at the level of the ventral horn of the cervico-thoracic and the lumbo-sacral intumescence, diffuse loss of myelinated axons at the level of the ventral funiculi of all segments of the spinal cord, and moderate diffuse astrocytic reaction. These findings confirmed the diagnosis of SMA. No mutation of the FVT1 gene was found on genetic analysis. Further study into the causative gene mutation of SMA in Blonde D'Aquitaine calves is under way. Identification of a novel genetic mutation could improve our understanding of the disease in human medicine.

Morphological alterations of the reticular thalamic nucleus in Engrailed-2 knockout mice.

The reticular thalamic nucleus (Rt) is a sheet of neurons that surrounds the dorsal thalamus laterally, along its dorso-ventral and rostro-caudal axes. It consists of inhibitory neurons releasing gamma-aminobutyric acid (GABA). This nucleus participates in the circuitry between the thalamus and the cerebral cortex, and its impairment is associated with neuro-psychiatric disorders. In this study, we investigated the Rt anatomy of Engrailed-2 knockout mice (En2-/- ), a mouse model of autism spectrum disorder (ASD), using parvalbumin as an immunohistochemical marker. We compared 4- and 6-week-old wild type (WT) and En2-/- mice using various morphometric parameters: cell area, shape factor, circularity and cell density. Significant differences were present in 6-week-old male mice with different genetic background (WT vs. En2-/- ): the Rt neurons of En2-/- mice showed a bigger cell area, shape factor and circularity when compared with WT. Age (4 weeks vs. 6 weeks) influenced the shape factor of WT females, the circularity and cell density of En2-/- males, and the shape factor and circularity of En2-/- females. Gender affected cell density in 4-week-old WT mice, shape factor and cellularity of 6-week-old WT mice, and cell area, shape factor and cell density of En2-/- at 6 weeks. Intrasubject (left-right) asymmetry of Rt was never observed. These results show for the first time that sex- and age-related changes occur in the Rt GABAergic neurons of the En2-/- ASD mouse model.

Footpad peripheral ganglioneuroblastoma in a dog.

BACKGROUND: Peripheral neuroblastic tumours arising from primitive cells of the cranial and spinal ganglia and from sympathetic ganglion cells of the autonomic nervous system include, from most to least differentiated, ganglioneuroma, ganglioneuroblastoma and neuroblastoma. Canine ganglioneuroblastoma has been described in the mediastinum, nasal and oral cavities, as well as in the brain. OBJECTIVE: To describe the clinical and histopathological findings, treatment and follow-up of a primary cutaneous ganglioneuroblastoma affecting the footpad of a dog. ANIMAL: An 8-year-old male German shepherd dog, referred for left forelimb lameness and licking of the footpad, showed thickening of the footpad of digit V with a central nodular lesion. METHODS AND RESULTS: Histopathological and immunohistochemical examination on a surgical skin biopsy specimen showed an infiltrative and highly cellular neoplasm in the deep dermis. The neoplasm was composed of large polyhedral cells with abundant cytoplasm containing Nissl substance that reacted strongly with neuron-specific enolase and neuronal nuclei antigen, spindle cells with indistinct cell borders suggestive of Schwann cells, with a mild S-100 and GFAP immunoreactivity, and rare nests of neuroblasts. The owner agreed to digit amputation. Histologically, a neoplastic multinodular proliferation with morphological findings like those detected in the biopsy was observed, not extended to the surgical margins and without involvement of skeletal bone. No recurrence or metastasis was observed over a period of one year. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first report of a primary cutaneous ganglioneuroblastoma in a dog. Ganglioneuroblastoma should be included in the differential diagnoses of canine footpad neoplastic diseases.

Mice as paratenic hosts of Aelurostrongylus abstrusus.

BACKGROUND: Several species of nematodes included in the superfamily Metastrongyloidea are recognized agents of parasitic infections in felines. Aelurostrongylus abstrusus is the most prevalent species affecting the respiratory system of domestic cats. The route of infection in cats is supposed to be through ingestion of gastropod intermediate or paratenic hosts. However, because gastropods are not the preferred preys of cats, rodents were suggested to play an important role as paratenic hosts in the biological cycle of A. abstrusus and in the epidemiology of aelurostrongylosis. RESULTS: Two studies were conducted to document histopathological tissue lesions in mice experimentally infected with A. abstrusus third-stage larvae (L3) (Study 1), and to determine larval counts in their organs (Study 2). Additionally, cats were fed with experimentally infected mice to assess their infectivity. Aelurostrongylus abstrusus L3 were recovered from the liver, spleen, brain, skeletal muscle and gastrointestinal tract tissues by artificial digestion, and heart, spleen and brain tested positive for A. abstrusus at molecular diagnosis. Multifocal encephalitis and meningitis and glial nodules were the most common histopathological lesions found in mice inoculated with A. abstrusus. All cats shed first-stage larvae of A. abstrusus after ingestion of mice inoculated with this nematode. CONCLUSIONS: In this study, we provide information on the anatomical localization, histopathological alterations and rate of recovery of A. abstrusus L3 in mice, and confirm their infectivity to cats (definitive hosts) after feeding on infected mice (paratenic hosts). Data presented here add knowledge to further understand the biology of A. abstrusus in mice and underline the importance of mice as paratenic hosts of this nematode for the infection of cats.