Interthalamic hematoma secondary to cerebrovascular atherosclerosis in an aged grizzly bear (Ursus arctos horribilis) with primary cardiac schwannoma.

A 38-year-old intact female Grizzly bear (Ursus arctos horribilis) was evaluated for progressive seizure activity, pale mucous membranes, deficient pupillary light and menace responses, and irregular shallow respiration. Because of poor response to treatment, the animal was euthanized. Gross examination revealed abundant hemorrhage in both lateral ventricles; a large, encapsulated mass within the rostral interthalamic region; and a well-demarcated, round white mass in the apex of the right ventricle. Histologic examination of the interthalamic mass revealed a resolving hematoma composed of stratified layers of fibrin and white blood cells that was surrounded by a thick fibrous capsule. Most meningeal and intraparenchymal blood vessels had multifocal degeneration, fragmentation, and fraying of the internal elastic lamina with prominent intimal proliferations and plaques. The plaques were formed by small numbers of lipid-laden macrophages (foam cells) that were intermixed with occasional lymphocytes and plasma cells. The cardiac mass was composed of pallisading and interlacing spindle cells with parallel nuclei and abundant, pale eosinophilic cytoplasm consistent with a schwannoma.

A case of primary hypothyroidism causing central nervous system atherosclerosis in a dog.

A 2-year-old, castrated male, Australian shepherd was presented with a history of chronic mild ataxia, obesity, and lethargy. The dog was treated with levothyroxine, but the ataxia worsened. Cranial nerve abnormalities developed and the dog was euthanized. Postmortem examination revealed marked thyroid gland atrophy and widespread, severe central nervous system atherosclerosis.

High fat and high fructose diet induced intracranial atherosclerosis and enhanced vasoconstrictor responses in non-human primate.

The present study examined the effect of high fat and high fructose (HFF) diet on the development of atherosclerosis and vascular contractile responses in the cerebral artery and thoracic aorta in non-human primates. Female cynomolgus monkeys (age: 3 to 4 years) were divided into normal control diet (N=5) and HFF diet groups (N=5). Twenty-eight weeks after feeding the HFF diet, total cholesterol and low-density lipoprotein-cholesterol in serum were significantly increased in the HFF diet group compared to the control group. The ultrastructural analyses of the basilar artery and aorta demonstrated the infiltration of lipid-laden foam cells and the appearance of lipid droplet-filled smooth muscle cells in the monkeys fed with the HFF diet. In terms of vascular reactivity, there was significantly greater vasoconstriction of the aorta and basilar artery in response to 5-hydroxytryptamine in the HFF diet group compared to the normal diet-fed group. In addition, KCl-induced vasoconstriction of the basilar arteries was also significantly enhanced in the HFF diet group compared to the normal diet-fed monkeys. In all, our present study has demonstrated that changes in the vascular responsiveness of the cerebral artery and its cellular architecture may manifest into cerebrovascular complications consistent with a pathological state normally observed with the onset and progression of atherosclerosis.

Sirolimus-eluting stents in the canine cerebral vasculature: a prospective, randomized, blinded assessment of safety and vessel response.

OBJECT: Use of the sirolimus-eluting stent has led to a reduction of in-stent stenosis following treatment of coronary atherosclerosis, whereas treatment of intracranial atherosclerosis with bare-metal stents results in excessive restenosis rates of approximately 40%. Neurotoxicity effects and vessel injury are unknown in the cerebral vasculature. To assess the safety profile and vascular effects of sirolimus-coated stents, the authors conducted a prospective comparative study in which drug-eluting and bare-metal stents were implanted in the canine basilar artery (BA). METHODS: Sixteen mongrel dogs were randomized (eight animals per group) to receive either bare-metal 1.5 x 8-mm (six-cell) stents or sirolimus-eluting stents of the same dimensions. Interventionists, histopathologists, and histopathology technicians who participated in the study were blinded to the stent characteristics. Stents were implanted in the canine BA. Serial peripheral blood samples were obtained during the 1st week after implantation to determine the time-dependent serum concentration of sirolimus. Follow-up angiographic studies were performed 30 days after stent implantation to assess the effects of stent placement on the BA and brainstem perforating vessels. Explantation of the stent and BA was performed immediately after angiography by using a pressurized formalin fixation procedure. Histological and computer-assisted morphometric analyses of specimens obtained in each animal were performed. Sirolimus could not be detected in peripheral blood samples obtained later than 24 hours posttreatment. On follow-up angiography, all perforating vessels observed on initial angiograms remained patent, and no evidence of parent vessel damage or pseudoaneurysm formation was observed. Explanted vessels and brainstem sections did not demonstrate evidence of histological neurotoxicity, such as gliosis or infarction. No significant differences were found in the time to endothelialization of bare-metal and sirolimus-coated stents. Smooth-muscle cell (SMC) proliferation, the putative agent for restenosis, was lower in animals receiving sirolimus-coated stents (p = 0.003). Additionally, intimal fibrin density was increased in the dogs treated with sirolimus-coated stents (p < 0.0001). Histological evidence of an inflammatory response demonstrated a trend toward a reduced response in the sirolimus group (mean 0.58) compared with the bare-metal group (mean 0.83, p = 0.33). CONCLUSIONS: No neurotoxic effects were observed in the intracranial vessel walls or brainstem tissue in which sirolimus-coated stents were implanted. Compared with bare-metal stents, the sirolimus-coated devices did not impair endothelialization and, furthermore, tended to reduce the proliferation of SMCs. These findings indicate that sirolimus-coated devices may inhibit in-stent stenosis. Further studies with longer-term follow up are required to assess the restenosis rates of sirolimus-coated stents implanted in the intracranial vasculature.

Cerebral arteriosclerosis in an aged captive polar bear (Ursus maritimus).

Cerebral arteriosclerosis was observed upon necropsy of a 36-yr-old female captive polar bear (Ursus maritimus) that developed a sudden onset of seizure-like activity and died. The medium and large cerebral arteries of the meninges had moderate to severe diffuse discoloration and mineralization of the matrix of the tunica media, with little or no associated cellular reaction. Scanning electron microscopy of the affected arteries showed discrete crystalline calcified deposits in the media and sclerosis of the arterial wall. There were no lesions in the brainstem. The findings suggested a sudden and rapidly fatal loss of blood flow to the brain caused by long-standing arterial lesions. Incidental findings included numerous 0.1- to 10-cm-diameter, hepatic cysts lined with hyperplastic biliary epithelium, a unilateral, unipolar, 3-cm-diameter renal tubular adenoma, and approximately 250 active Baylisascaris sp. nematodes in the intestines.

Neurologic manifestations of cerebrovascular atherosclerosis associated with primary hypothyroidism in a dog.

A 6-year-old, obese, spayed female Doberman pinscher dog was presented for clinical examination with a 1-day history of repeated seizures and a long-term history of periodic bouts of ataxia, circling, and head tilt. The seizures were controlled with phenobarbital, but the dog died 2 days after presentation. Necropsy revealed severe, diffuse, follicular atrophy of the thyroid gland (primary hypothyroidism), severe generalized atherosclerosis, severe pseudolaminar cortical necrosis and acute vasculitis in the cerebrum, and congestive heart failure. The neurologic signs were explained by the pseudolaminar necrosis and associated cerebrovascular atherosclerosis. The cerebrocortical necrosis was believed to be caused by tissue hypoxia secondary to progressive vascular occlusion. Cerebrovascular atherosclerosis, secondary to primary hypothyroidism, was considered the most important cause of the hypoxia.

Coronary, aortic and cerebral atherosclerosis in swine of 3 age-groups: implications.

CORONARY, AORTIC AND INTERCRANIAL ATHEROSCLEROSIS HAS BEEN COMPARED IN SWINE MAINTAINED UNDER THE FOLLOWING CONDITIONS: (1) adequate food and housing but animals held in test social situations for 1 year; postmortem examination at ages of 13 to 15 months; (2) food and management designed for high productivity; postmortem examination at ages of 6 to 9 years; (3) an outdoor system of husbandry and a cooked garbage diet; postmortem examination at ages of 8 to 14 years.Extramural coronary, aortic and intracranial atherosclerosis was most advanced in swine that were fed garbage. Cerebral infarction (cerebromalacia) also was most advanced in these swine but developed in swine of the younger groups in which it was associated with atherosclerosis of small intracranial extracerebral arteries rather than with stenosis of the larger intracranial extracerebral arteries as in the oldest swine. The lesions of atherosclerosis in swine of these 3 age-groups form a continuous series and are morphologically identical with corresponding stages of atherosclerosis of man.It is concluded that swine can replace non-human primates as subjects for studies of atherosclerotic vascular disease, and that experimental designs must allow for age and behaviour patterns of the species.