Immunohistochemical Characterization of Immune Cell Infiltration in Feline Glioma.

The relationship between inflammatory cells and tumour biology has been defined in many human intracranial neoplasms, but it is relatively poorly characterized in veterinary medicine. The aim of this study was to define the immune cell infiltration in cases of feline glioma and its possible association with tumour morphology and type. A retrospective search identified 18 gliomas that met inclusion criteria. Tumours were subjected to immunohistochemistry (IHC) for CD3, CD20, Iba1, MAC387 and factor VIII-related antigen. For each antibody, the number of labelled cells was counted in 10 high-power (×400) fields and a cumulative score for each antibody was generated. Intratumoural and peritumoural CD3+ T lymphocytes were observed in all cases and occurred primarily within perivascular spaces and rarely around areas of necrosis or leptomeningeal spread. Perivascular CD20+ B lymphocytes were detected in 12/18 (67%) cases and occurred within and around tumours and near areas of leptomeningeal spread. MAC387 immunoreactivity highlighted intravascular monocytes in 9/18 (50%) cases, but failed to highlight tumour-associated macrophages. Intratumoural and peritumoural Iba1 immunoreactivity was observed in all cases, with increased overall intensity around areas of necrosis and leptomeningeal spread. Intratumoural and peritumoural factor VIII-related antigen immunoreactivity was also detected in all cases and was concentrated in areas of microvascular proliferation and necrosis. No significant associations were found between IHC scores for immune cells (i.e. lymphocytes and macrophages) and tumour morphology and type. Average factor VIII reactivity was higher in astrocytomas than oligodendrogliomas (P = 0.003).

Putative Cerebral Microbleeds in Dogs Undergoing Magnetic Resonance Imaging of the Head: A Retrospective Study of Demographics, Clinical Associations, and Relationship to Case Outcome.

BACKGROUND: Cerebral microbleeds (CMBs) are focal intraparenchymal signal voids on gradient-echo magnetic resonance imaging (MRI), corresponding to regions of chronic hemorrhage. In humans, they are associated with systemic disease and shorter survival times. Although similar findings have been identified in dogs, their epidemiology and clinical correlations have not been investigated. OBJECTIVE: To determine epidemiological features, clinical associations, and associations with outcome for putative CMB-like foci (putative microbleeds [pMBs]) identified by T2*-weighted MRI in dogs. ANIMALS: Five hundred and eighty-two dogs undergoing 3T brain MRI between 2011 and 2016. METHODS: Retrospective case-control study. Demographic, diagnostic, and clinicopathological data were obtained from medical records and phone follow-up. Demographic variables were compared between dogs with and without evidence of pMBs. For dogs with such evidence, and a subset of matched controls, associations with clinical presentation, concurrent disease, and survival times were evaluated. RESULTS: Dogs with pMBs were older (P < .001) and smaller (P = .004) than unaffected dogs. Compared to matched controls, they presented more frequently for vestibular signs (P = .030). Cortical atrophy occurred concurrently with pMBs in 26% (14/54) of dogs. Diagnosed renal disease was not significantly associated with pMBs, but proteinuria was more common in dogs with pMBs than in matched controls (odds ratio = 3.01, P = .005). Dogs with pMBs had a shorter median survival time than did matched controls (P = .011). CONCLUSIONS AND CLINICAL IMPORTANCE: Putative microbleeds occurred in 54 of 582 (9.3%) of dogs undergoing brain MRI, but may not be a normal consequence of aging. They were associated with shorter survival time and proteinuria in the study population.

Molecular signalling pathways in canine gliomas.

In this study, we determined the expression of key signalling pathway proteins TP53, MDM2, P21, AKT, PTEN, RB1, P16, MTOR and MAPK in canine gliomas using western blotting. Protein expression was defined in three canine astrocytic glioma cell lines treated with CCNU, temozolamide or CPT-11 and was further evaluated in 22 spontaneous gliomas including high and low grade astrocytomas, high grade oligodendrogliomas and mixed oligoastrocytomas. Response to chemotherapeutic agents and cell survival were similar to that reported in human glioma cell lines. Alterations in expression of key human gliomagenesis pathway proteins were common in canine glioma tumour samples and segregated between oligodendroglial and astrocytic tumour types for some pathways. Both similarities and differences in protein expression were defined for canine gliomas compared to those reported in human tumour counterparts. The findings may inform more defined assessment of specific signalling pathways for targeted therapy of canine gliomas.

Visual response latencies of magnocellular and parvocellular LGN neurons in macaque monkeys.

Signals relayed through the magnocellular layers of the LGN travel on axons with faster conduction speeds than those relayed through the parvocellular layers. As a result, magnocellular signals might reach cerebral cortex appreciably before parvocellular signals. The relative speed of these two channels cannot be accurately predicted based solely on axon conduction speeds, however. Other factors, such as different degrees of convergence in the magnocellular and parvocellular channels and the retinal circuits that feed them, can affect the time it takes for magnocellular and parvocellular signals to activate cortical neurons. We have investigated the relative timing of visual responses mediated by the magnocellular and parvocellular channels. We recorded individually from 78 magnocellular and 80 parvocellular neurons in the LGN of two anesthetized monkeys. Visual response latencies were measured for small spots of light of various intensities. Over a wide range of stimulus intensities the fastest magnocellular response latencies preceded the fastest parvocellular response latencies by about 10 ms. Because parvocellular neurons are far more numerous than magnocellular neurons, convergence in cortex could reduce the magnocellular advantage by allowing parvocellular signals to generate detectable responses sooner than expected based on the responses of individual parvocellular neurons. An analysis based on a simple model using neurophysiological data collected from the LGN shows that convergence in cortex could eliminate or reverse the magnocellular advantage. This observation calls into question inferences that have been made about ordinal relationships of neurons based on timing of responses.