Objective: To determine whether angiogenesis and microglial activation were related to seizure-induced neuronal death in the cerebral cortex of Shetland Sheepdogs with familial epilepsy. Animals: Cadavers of 10 Shetland Sheepdogs from the same family (6 dogs with seizures and 4 dogs without seizures) and 4 age-matched unrelated Shetland Sheepdogs. Procedures: Samples of brain tissues were collected after euthanasia and then fixed in neutral phosphate–buffered 10% formalin and routinely embedded in paraffin. The fixed samples were sectioned for H&E staining and immunohistochemical analysis. Results: Evidence of seizure-induced neuronal death was detected exclusively in samples of cerebral cortical tissue from the dogs with familial epilepsy in which seizures had been observed. The seizure-induced neuronal death was restricted to tissues from the cingulate cortex and sulci surrounding the cerebral cortex. In almost the same locations as where seizure-induced neuronal death was identified, microvessels appeared longer and more tortuous and the number of microvessels was greater than in the dogs without seizures and control dogs. Occasionally, the microvessels were surrounded by oval to flat cells, which had positive immunohistochemical results for von Willebrand factor. Immunohistochemical results for neurons and glial cells (astrocytes and microglia) were positive for vascular endothelial growth factor, and microglia positive for ionized calcium–binding adapter molecule 1 were activated (ie, had swollen cell bodies and long processes) in almost all the same locations as where seizure-induced neuronal death was detected. Double-label immunofluorescence techniques revealed that the activated microglia had positive results for tumor necrosis factor-α, interleukin-6, and vascular endothelial growth factor receptor 1. These findings were not observed in the cerebrum of dogs without seizures, whether the dogs were from the same family as those with epilepsy or were unrelated to them. Conclusions and Clinical Relevance: Signs of angiogenesis and microglial activation corresponded with seizure-induced neuronal death in the cerebral cortex of Shetland Sheepdogs with familial epilepsy. Microglial activation induced by vascular endothelial growth factor and associated proinflammatory cytokine production may accelerate seizure-induced neuronal death in dogs with epilepsy.

Objective—To characterize the dynamics of calcitonin secretion in response to experimentally induced hypercalcemia in cats. Animals—13 healthy adult European Shorthair cats.Procedures—For each cat, the calcitonin response to hypercalcemia (defined as an increase in ionized calcium concentration > 0.3mM) was investigated by infusing calcium chloride solution and measuring circulating calcitonin concentrations before infusion (baseline) and at various ionized calcium concentrations. Calcitonin expression in the thyroid glands of 10 of the cats was investigated by immunohistochemical analysis. Results—Preinfusion baseline plasma calcitonin concentrations were very low in many cats, sometimes less than the limit of detection of the assay. Cats had a heterogeneous calcitonin response to hypercalcemia. Calcitonin concentrations only increased in response to hypercalcemia in 6 of 13 cats; in those cats, the increase in calcitonin concentration was quite variable. In cats that responded to hypercalcemia, calcitonin concentration increased from 1.3 ± 0.3 pg/mL at baseline ionized calcium concentration to a maximum of 21.2 ± 8.4 pg/mL at an ionized calcium concentration of 1.60mM. Cats that did not respond to hypercalcemia had a flat calcitonin-to-ionized calcium concentration curve that was not modified by changes in ionized calcium concentration. A significant strong correlation (r = 0.813) was found between the number of calcitonin-positive cells in the thyroid gland and plasma calcitonin concentrations during hypercalcemia. Conclusions and Clinical Relevance—Healthy cats had very low baseline plasma calcitonin concentrations. A heterogeneous increase in plasma calcitonin concentration in response to hypercalcemia, which correlated with the expression of calcitonin-producing cells in the thyroid, was identified in cats.