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 examine renal expression of α-smooth
muscle actin (α-SMA) and fibronectin in cats with
tubulointerstitial nephritis (TIN) for use in predicting
progression to renal fibrosis.
Animals—19 cats with TIN and 9 cats without nephritis.
Procedure—Serum creatinine and BUN concentrations
were measured. Indices for glomerular extra-cellular
matrix (ECM), tubular injury (TI), and fibronectin were
determined in renal specimens to quantify the extent of
injury and fibrotic lesions. Expression of α-SMA in renal
tissue was immunohistochemically detected, and correlations
were evaluated between the α-SMA index and
other histologic and clinical variables.
Results—The α-SMA index in tubulointerstitial areas
(1.63 ± 0.78) was significantly higher in cats with TIN,
especially in the periglomerular and peritubular areas,
than in cats without nephritis (0.20 ± 0.14). The
α-SMA index was significantly associated with the TI
index (r2 = 0.70), fibronectin index (r2 = 0.95), BUN concentration
(r2 = 0.64), and serum creatinine concentration
(r2 = 0.66). Of special interest was that interstitial
α-SMA expression appeared evident in the kidneys at an
early stage of TIN, prior to the onset of ECM deposition.
Conclusion and Clinical Relevance—Analysis of
results of histologic and clinical examinations
revealed that interstitial α-SMA expression may have
clinical importance and may be a useful early histologic
marker for development of chronic renal failure
in cats. An immunohistochemical examination for
fibrogenic molecules (such as α-SMA expression)
may provide fundamental information on the pathogenesis
of early-stage renal disease and aid clinical
management of cats with chronic renal failure, including
TIN. (Am J Vet Res 2000;61:1080–1086)