Intracytoplasmic neuronal inclusions in woodchuck brain stem.

Homogenous eosinophilic intracytoplasmic inclusion bodies were found within the large reticular neurons of the brain stems of 57 captive woodchucks (Marmota monax). Light microscopy was consistent with a proteinaceous nature, while electron microscopy suggested a non-viral origin. The woodchucks with inclusions were older than the general population that was studied. It is hypothesized that the neuronal inclusions in the brain stem are indicative of nonspecific ageing changes.

Experimental radiation injury: combined MR imaging and spectroscopy.

A model of radiation injury to the brain was developed in the cat. Definite radiation changes were demonstrated at magnetic resonance (MR) imaging in four of six cats. These changes consisted of high-intensity abnormalities on images obtained with a long repetition time (TR) and a long echo time (TE), which were initially noted 208-285 days after irradiation. These changes were associated with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement on short TR and inversion-recovery (IR) pulse sequences. Gd-DTPA enhancement and the high intensity on the long TR/TE images were identified at the same time and became more prominent throughout the study. Chemical-shift imaging and phosphorus spectroscopy demonstrated no notable changes despite clear-cut MR evidence of abnormalities. Sodium imaging was positive in one case. Correlation of MR and pathologic findings revealed areas of radiation necrosis and wallerian degeneration that corresponded to areas of Gd-DTPA enhancement on short TR and IR images and to areas of high intensity on long TR/TE images. Peripheral to the areas of Gd-DTPA enhancement were nonenhanced zones of high-signal-intensity abnormality on long TR/TE images, which represented regions of demyelination without necrosis. Gd-DTPA-enhanced proton imaging was the most sensitive method for detecting radiation damage in this animal model.

Computed tomography, magnetic resonance imaging, and pathologic observations of the effects of intrathecal metrizamide and iohexol on the canine central nervous system.

A two-group crossover design experiment was used in eight dogs to compare the effects of intrathecally injected (0.25 mL/kg, 180 mg I/mL) metrizamide and iohexol. Additional acute observations were made in four of the dogs following a high dose (0.45 mL/kg of 300 mg I/mL) of each agent. In computed tomographic observations, there was progressive passage of each contrast medium across the interface between the cerebrospinal fluid and the brain, and statistically identical levels of each contrast medium were present in the cerebral gyri. There was a similar passage of contrast medium across the interface between the cerebrospinal fluid and the spinal cord. The rate of passage of each agent into the brain parenchyma suggested their active transport rather than a simple diffusion. In both T2-weighted magnetic resonance imaging and histopathologic studies, there was no evidence of cerebral edema following either high or low doses of each agent. In T1-weighted images made following the intravenous injection of gadolinium-DTPA (0.1 mmol/kg), the blood-brain barrier was intact.

MR of brain radiation injury: experimental studies in cats.

Two of six cats receiving small-field, single-dose, brain irradiation of 35 Gy with 6 MeV photons developed brain abnormalities in the irradiated area on MR images at 6 and 8 months, respectively, after treatment. The lesions were of high intensity on T2-weighted images and did not enhance after IV administration of gadolinium-DTPA. An additional lesion in one of these cats displayed high signal on T2-weighted images and enhanced on T1-weighted images after IV gadolinium-DTPA. Pathologic correlation revealed that the nonenhancing T2-weighted lesions consisted of edema or demyelinated regions without inflammation while the gadolinium-enhanced lesion demonstrated necrosis with inflammatory infiltrate. Focal brain irradiation may produce noninflammatory demyelination and necrosis. These histologic entities may be potentially distinguished on MR with IV gadolinium-DTPA.

Hemorrhage and edema in acute spinal cord compression: demonstration by MR imaging.

Until the development of magnetic resonance (MR) imaging there was no nondestructive technique for monitoring the pathologic response to acute spinal cord trauma. The characteristic findings of hemorrhage, necrosis, and edema have been well described in animal models. We used a 1.4-T, animal imaging system to study acute cord contusions in rats. Contusions were induced by means of extradural aneurysm clip compression, and imaging was performed 3-5 hours after injury with short and long spin-echo (SE) sequences. Animals were killed immediately after imaging, and the gross anatomic and histologic findings were correlated with image appearances. On long SE sequences edema appeared as an area of high signal intensity that extended proximal and distal to the site of contusion. At the contusion site there was focal intraparenchymal hemorrhage which had low signal intensity on T2-weighted images, presumably owing to deoxyhemoglobin. MR imaging can be used to assess pathologic changes resulting from acute cord contusion and to aid in differentiating irreversible damage (hemorrhage) from potentially reversible edema.

Subchronic toxicity studies of N-D-ornithyl amphotericin B methyl ester in dogs and rats.

Two subchronic studies were conducted to assess the potential toxicity of N-D-ornithyl amphotericin B methyl ester (OAME). In both studies the comparative control substance was amphotericin B (AMB). Dogs (5/sex/group) were given OAME (82% pure, based on high-pressure liquid chromatographic (HPLC) analysis) at 0.6, 2.5, and 10 mg/kg or AMB at 0.6 mg/kg intravenously once daily for 3 months. Two dogs per sex per group were retained for a 7-week postdose observation period. Rats (15/sex/group) were given daily doses of OAME at 4, 12, 24, and 36 mg/kg or AMB at 5 and 12 mg/kg intraperitoneally for 3 months. The principal organs of toxicity in both species were the liver, kidneys, and circulating erythrocytes. Hepatic changes in dogs consisted of periportal and centrilobular inflammation in animals of all dosed groups and were equivalent in dogs given 0.6 mg/kg OAME or AMB. In rats, acute hepatic necrosis with periportal, centrilobular, or panlobular distribution in animals of all OAME (except 4 mg/kg) and AMB-dosed groups was observed. These changes were equivalent in the 36-mg/kg OAME- and 12-mg/kg AMB-dosed animals. Renal changes, evidenced by increases in serum urea nitrogen water consumption, urine volume, decreased urine osmolality, and renal tubular changes (ranging from degeneration and regeneration to necrosis), were observed in both species. In dogs, these changes in the OAME-dosed animals were less severe at all doses than those observed in the AMB-dosed dogs. Renal changes in rats, which were mild in comparison to the dogs, were equivalent at doses of 5 and 12 mg/kg AMB and 36 mg/kg OAME. Decreased erythrocyte counts, hematocrit, and hemoglobin values were observed in both species. Unique to the dog study, however, were irreversible behavioral (somnolence, ataxia, tremors, and compulsive searching) and/or morphologic brain changes (gliosis with astrocytic hypertrophy and hyperplasia) at doses of 2.5 and 10 mg/kg OAME. Similar changes were observed in two dogs given 10 mg/kg OAME (100% pure, based on HPLC analysis) in a 6-week pilot study, indicating that the neurological changes were induced by OAME rather than by an impurity. These changes appear related to prolonged exposure to high plasma concentrations of OAME.

Craniopharyngioma in a dog.

Craniopharyngiomas are rare in dogs. A 3 cm suprasellar craniopharyngioma in a 13-month-old male mongrel dog is described. The mass consisted of multiple microcysts and solid areas with mesenchymal proliferation in areas of transition. Tumour cells were arranged in solid sheets or separated into islands by thick bands of collagen. Squamous differentiation of tumour cells with keratin formation and a focus of osseous metaplasia were present. Occasionally, tumour cells were arranged in rosettes. Cysts were lined by a single layer of cuboidal to low columnar epithelium and contained proteinaceous fluid with numerous cholesterol clefts. The diagnosis was based on age of occurrence, location and histological appearance.

A morphologic classification of brain tumors found in several strains of mice.

Brain tumors were found in 42 mice from a total study population of 77,410 mice, which included several strains (BALB/c, C3H, C57BL/6, and hybrids of these strains). The brain tumors were classified on the basis of the new World Health Organization classification of human brain tumors. Tumors originated from neuroepithelial and meningeal tissues, blood vessels, and germ cells. The youngest animal with a tumor was 111 days of age. The tumor incidence was low, being 0.054% of the total study population, with 0.067% in controls and 0.052% in treated mice. Lipomas were the most common type of tumor diagnosed, and they were considered to represent hamartomas rather than true neoplasms. There were 27 brain tumors other than lipomas, the majority (16) of which occurred in BALB/c mice, whereas meningeal tumors (6) were confined to C3H and hybrid strains of mice. The morphologic characteristics of each tumor type are presented.

Canine GM2-gangliosidosis: chemical and enzymatic features.

The chemical and enzymatic features in tissues of GM2-gangliosidosis are characterized by the analysis of glycolipids and FD-MS, and also by enzymatic analysis with DEAE-Sepharose column chromatography. The results suggest that canine GM2-gangliosidosis is equivalent to human juvenile GM2-gangliosidosis.

Meningiomas in young cats with mucopolysaccharidosis I.

Meningiomas are the most common central nervous system tumor of the cat, with an age at diagnosis of greater than nine years in 73% of the affected animals. Four of seven cats with alpha-L-iduronidase deficient mucopolysaccharidosis I had meningiomas at postmortem examination. All four cats were less than three years of age. The relationship between the meningiomas and the metabolic defect of MPS I is not clear.

Mycotic encephalitis in weanling rats.

An outbreak of mycotic encephalitis occurred in rats 15-31 da old. Eight of 170 rats born within a 2-wk period had histologically proven mycotic encephalitis with the characteristics of phycomycosis (mucormycosis). No mycotic lesions were seen in the lungs or organs other than the brain.

Tumours of the nervous system.

Tumours of the nervous system of animals are not as rare as has been commonly believed. In dogs, especially the brachycephalic breeds, these tumours occur as frequently as in man. The tumours are grouped according to tissue of origin as follows: nerve cells, neuroepithelium, glia, peripheral nerves and nerve sheaths, meninges and vessels, the pineal and pituitary glands, and the craniopharyngeal duct. Tumours of the glia are relatively common and are divided into the following types: astrocytoma, oligodendroglioma, glioblastoma, spongioblastoma, medulloblastoma, and unclassified gliomas.