This review of human and cat rabies from 1986 to 2022 has shown mostly AgV3 variant in human cases with 29/45 (64.4%) reports including 23 from bats, four from cats, and two from unknown species, followed by 8/45 (17.8%) of AgV2 variant (all from dogs), 4/45 from marmoset variant (all from Callithrix jacchus), 2/45 samples compatible with wild canid variant (both from Cerdocyon thous), and one/45 of AgV1 variant from a domestic dog. Only one sample of human rabies was not typified, related to bat aggression. In addition, surveillance conducted in the state of São Paulo confirmed the presence of rabies in 7/23,839 cats (0.031%) and 3/106,637 dogs (0.003%) between 2003 and 2013, with a 10:1 overall cat-to-dog positivity ratio. This 10-fold higher infection rate for cat rabies may be explained by cats’ hunting habits and predation. In addition, after 28 years of rabies-free status, a new cat rabies case was reported in the city of São Paulo in 2011. The rabid cat lived, along with other pets, in a household located near the largest downtown city park, whose owners presented animal hoarding behavior. Thus, animal hoarders and rescuers, public health agents, animal health professionals, and the general population with contact need to be aware of the risk of bat-borne rabies followed by spillover from cats to humans. In conclusion, cat rabies cases are becoming increasingly important in Brazil. This poses a One Health concern, given the overlapping of human, bat and cat populations within the same predisposed environment.

Neospora caninum is an apicomplexan protozoan that is considered one of the main agents responsible for abortion in ruminants. The lesions found in the central nervous system (CNS) of aborted fetuses show multifocal necrosis, gliosis, and perivascular cuffs of mononuclear cells, but the inflammatory and glial cells have not been immunophenotypically characterized. The lesions in the CNS of infected adult animals have rarely been described. Therefore, in this study, we characterized the lesions, the immunophenotypes of the inflammatory and glial cells and the expression of MHC-II and PCNA in the CNS of goats infected with N. caninum. The CNS of eight aborted fetuses and six adult male goats naturally infected with N. caninum were analyzed with lectin histochemistry (RCA1) and immunohistochemistry (with anti-CD3, −CD79α, −GFAP, −MHC-II, and -PCNA antibodies). All animals were the offspring of dams naturally infected with N. caninum. The microscopic lesions in the CNS of the aborted fetuses consisted of perivascular cuffs composed mainly of macrophages (RCA1+), rare T lymphocytes (CD3+), and rare B lymphocytes (CD79α+). Multifocal necrosis surrounded by astrocytes (GFAP+), gliosis composed predominantly of monocytic-lineage cells (macrophages and microglia, RCA1+), and the cysts of N. caninum, related (or not) to the lesions were present. Similar lesions were found in four of the six male goats, and multinucleate giant cells related to focal gliosis were also found in three adult goats. Anti-GFAP immunostaining showed astrocytes characterizing areas of glial scarring. Cysts of N. caninum were found in three adult male goats. The presence of N. caninum was evaluated with histopathology, immunohistochemistry, and PCR. Immunohistochemistry demonstrated anti-PCNA labeling of macrophages and microglia in the perivascular cuffs and the expression of MHC-II by microglia and endothelial cells in the CNS of the aborted fetuses and adult male goats. Macrophages and microglia were the predominant inflammatory cells in the CNS of aborted fetuses and healthy adult male goats infected with N. caninum. Activated astrocytes were mainly associated with inflamed areas, suggesting that astrocytes were involved in the resolution of the lesions.

β-amyloid (Aβ) can accumulate in the brain of aged dogs, and within vessels walls, the disease is called cerebral amyloid angiopathy (CAA). In humans, Alzheimer’s disease and CAA are strongly correlated with cerebrovascular disease. However, in dogs, this association has not been extensively studied yet. The present report highlights the pathological and clinical features of a concomitant cerebrovascular disease and amyloid precursor protein (APP) accumulation in the brain of a dog. A female, 16-year-old, Standard Poodle with a one-year history of cognitive deficits presented with an acute onset of right-sided postural reaction deficit and circling, left-sided head tilt, positional nystagmus, and ataxia. Due to poor prognosis the dog was euthanized, and pathological examination of the brain revealed an acute lacunar infarction within the thalamus extending to rostral colliculus. Additional findings included subacute and chronic areas of ischemia throughout the brain and areas of hemorrhage within the medulla. Immunolabeling revealed APP deposition within intraparenchymal vessels of frontal, temporal and occipital cortex, hippocampus, diencephalon, mesencephalon and myelencephalon, besides meningeal vessels walls. Glial fibrillary acidic protein (GFAP) immunolabeling showed marked astrocytosis around the acute area of infarction and within chronic areas of ischemia. Histological examination of the brain along with immunohistochemistry results showed a concomitant APP, which is an Aβ precursor, accumulation within the neuroparenchyma and vessels (CAA) with histological evidences of a cerebrovascular disease in an aged dog. This report shows that APP accumulation in the brain can occur concomitantly to a severe cerebrovascular disease in a dog. Further studies are necessary to elucidate if cerebrovascular disease is associated with Aβ accumulation in the brain of dogs.

Objectives: The aim of the study was to evaluate central nervous system (CNS) lesions in non-effusive and effusive cases of feline infectious peritonitis (FIP) regarding aspects related to astrocytic and microglial reactions. Methods: Five necropsied cats that were naturally infected with FIP virus, confirmed by reverse transcriptase polymerase chain reaction and immunohistochemistry, with different intensities of CNS lesions, were studied. Brain and cerebellum were evaluated by light microscopy and immunohistochemistry for glial fibrillary acidic protein (GFAP) and vimentin to assess astrocytic morphology, and lectin histochemistry for Ricinus communis agglutinin-I (RCA-I) to detect microglia was performed to evaluate the glial response in the CNS of cats with FIP. Results: An important astrocytic response in many areas of the CNS of all cats, including the periventricular areas of lateral ventricles and fourth ventricle, the molecular layer of the cerebellum and cerebral cortex, was visualized. This astrocytic reactivity was associated with areas of granulomatous or pyogranulomatous vasculitis/perivasculitis in most cases, and it was characterized by multifocal to coalescing astrocytosis and astrogliosis with an increase in the expression of intermediate filaments, such as GFAP. However, astrocytes exhibited strong vimentin expression in neuroparenchyma with severe inflammatory and necrotic changes, but GFAP expression was mild or absent in these cases. A microglial response was present only in severe lesions, and RCA-I expression was detected primarily in gitter cells and resting microglia. Conclusions and relevance: The present study indicates a strong astrocytic response, including the presence of many less differentiated vimentin-positive astrocytes and gitter cells positive for RCA-1 in severe lesions in the CNS of cats with FIP.

Equine herpesvirus type 1 (EHV-1) is an emerging pathogen that causes encephalomyelitis in horses and non-equid species. Several aspects of the immune response in the central nervous system (CNS), mainly regarding the role of inflammatory mediators during EHV-1 encephalitis, remain unknown. Moreover, understanding the mechanisms underlying extensive neuropathology induced by viruses would be helpful to establish therapeutic strategies. Therefore, we aimed to evaluate some aspects of the innate immune response during highly neurovirulent EHV-1 infection. C57BL/6 mice infected intranasally with A4/72 and A9/92 EHV-1 strains developed a fulminant neurological disease at 3 days post-inoculation with high viral titres in the brain. These mice developed severe encephalitis with infiltration of monocytes and CD8⁺ T cells to the brain. The inflammatory infiltrate followed the detection of the chemokines CCL2, CCL3, CCL4, CCL5, CXCL2, CXCL9 and CXCL-10 in the brain. Notably, the levels of CCL3, CCL4, CCL5 and CXCL9 were higher in A4/72-infected mice, which presented higher numbers of inflammatory cells within the CNS. Pro-inflammatory cytokines, such as interleukins (ILs) IL-1α, IL-1β, IL-6, IL-12β, and tumour necrosis factor (TNF), were also detected in the CNS, and Toll-like receptor (TLR) TLR2, TLR3 and TLR9 genes were also upregulated within the brain of EHV-1-infected mice. However, no expression of interferon-γ (IFN-γ) and IL-12α, which are important for controlling the replication of other herpesviruses, was detected in EHV-1-infected mice. The results show that the activated innate immune mechanisms could not prevent EHV-1 replication within the CNS, but most likely contributed to the extensive neuropathology. The mouse model of viral encephalitis proposed here will also be useful to study the mechanisms underlying extensive neuropathology.

Uma vez que muitos dos aspectos envolvidos na patogenia dos processos desmielinizantes do sistema nervoso central (SNC) são ainda pouco esclarecidos e que os astrócitos parecem estar envolvidos na mediação de tais processos, este estudo analisou morfologicamente a participação astrocitária na desmielinização do SNC por meio da marcação imunoistoquímica de duas proteínas dos filamentos intermediários astrocitários - a proteína glial fibrilar ácida (GFAP) e a vimentina (VIM) -, comparando amostras de cerebelo e de tronco encefálico de oito cães com cinomose e de dois cães normais, de diferentes raças e com idades entre um e quatro anos. Cortes histológicos dos tecidos foram submetidos à marcação pelo método indireto da avidina-biotina-peroxidase (ABC) e a reatividade astrocitária, observada em microscopia de luz, foi quantificada em um sistema computacional de análise de imagens. Observou-se, na maioria dos cortes de animais doentes, a presença de lesões degenerativas compatíveis com desmielinização. A marcação para a GFAP e para a VIM foi mais intensa nos animais com cinomose do que nos animais normais, especialmente nas regiões circunventriculares e nas adjacentes às áreas de degeneração tecidual. Não houve diferença significativa entre a imunomarcação (GFAP e VIM) dos animais com cinomose com e sem infiltração inflamatória da substância branca do cerebelo. O aumento da imunorreatividade dos astrócitos para a GFAP e a reexpressão de VIM nas áreas lesionais indicam o envolvimento astrocitário na resposta do tecido nervoso às lesões desmielinizantes induzidas pelo vírus da cinomose (CDV) no SNC.