Morphometric analysis of the developing rat brain.

In 2 studies, a method of linear morphometry was applied to regulatory developmental neurotoxicity studies in the rat. The first study involved the development of the brain during postnatal days (PNDs) 7-63, and the second involved the effects of 8 mg/kg i.p. trimethyltin chloride (TMT) to rats at PND 8, with morphometry performed at PNDs 12 and 24. The results of the TMT linear morphometry were compared with those from stereologic counting of neurons in the cerebral cortex, piriform cortex, and hippocampus. Stereology produces more meaningful data than simple linear morphometry for use in the regulatory assessment of the developmental neurotoxicity potential of compounds.

Neuroprotection afforded by MK-801 against L-2-chloropropionic acid-induced cerebellar granule cell necrosis in the rat.

Administration of a single oral dose of 750 mg/kg L-2-chloropropionic acid (L-CPA) to rats produces marked necrosis to the granule cell layer of the cerebellum by 48 h after dosing. Associated with the neuropathology the rats show locomotor impairment and a loss of body weight and a significant increase in cerebellar water and sodium content, indicating an oedematous reaction. Cerebellar aspartate and glutamate concentrations were reduced, while glycine and glutamine concentrations were increased after this treatment. Administration of the N-methyl-D-aspartate (NMDA) receptor channel antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,1 0-imine (MK-801), 30 min prior to L-CPA at a dose of 0.5, 1 or 5 mg/kg i.p. prevented the necrosis to the granule cell layer of the cerebellum and the signs of motor incoordination. Similarly there was no loss in cerebellar aspartate or glutamate concentration or increase in water or sodium content. Prior treatment with MK-801 at 0.1 mg/kg did not afford protection against the neurotoxicity. Post-treatment with 1 mg/kg MK-801 up to 1 h after administering L-CPA afforded complete neuroprotection, however if delayed until 2 or 6 h it gave only partial protection, and after 12 h it gave no protection. Administration of MK-801 alone at 5 mg/kg i.p., did not alter water content, sodium concentration, aspartate or glutamate concentrations in the cerebellum. In conclusion, we have shown that MK-801 given prior to and 1 h after L-CPA can afford complete neuroprotection, suggesting that a sub-population of NMDA receptors located on granule cells in cerebellum play a key role in mediating the selective toxicity of this chemical to the rat cerebellum.

Spastic syndrome in a Holstein bull: a histologic study.

A 4-year-old Canadian holstein bull developed the spastic syndrome, an episodic but progressive disorder causing pelvic limb muscular spasms. A post-mortem study, including morphometry of skeletal muscles and teased peripheral nerve fibers of the pelvic limb, revealed mild type II skeletal muscle fiber atrophy and minimal, focal segmental demyelination with remyelination, and axonal degeneration in peripheral nerves. Such alterations are probably incidental or age-associated. Idiopathic muscular cramps is the most probable explanation of the clinical disease and is consistent with the absence of significant morphologic pathologic lesions.

Experimental microcyst sarcocystis infection in lambs: pathology.

Six 34- to 42-day-old lambs raised in coccidia-free conditions were inoculated with 70,000 sporocysts derived from sheep heart with microscopic sarcocysts. Fever and mild anorexia occurred between 25 and 33 days after inoculation. A transient anaemia was most marked 32 days after inoculation. Lambs were killed and examined 14, 25, 33, 42, 60 and 81 days after inoculation. Gross lesions were absent. First and second generation meronts were present in endothelial cells at 25 and 33 days after inoculation. Meronts were most numerous in kidney glomeruli. Developing sarcocysts were rare at 42 days after inoculation. Sarcocysts with a primary cyst wall 2 to 3 micron thick composed of palisade projections were common at 60 and 81 days after inoculation in striated muscle and brain. Mild to severe striated muscle myositis and non-suppurative encephalitis or encephalomyelitis with glial nodules were observed 25 to 81 days after inoculation. Sarcocyst frequency varied considerably; it was highest in myocardium, M vastus intermedius, M vastus medialis, M extensor carpi radialis and tongue muscle and was lowest in M masseter.

'Kangaroo gait' in ewes: a peripheral neuropathy.

The clinical and pathological features of two lactating ewes with 'kangaroo gait', a locomotory disorder, are described, along with brief details of two further archival cases. Clinical neuropathological signs were consistent with a bilateral radial paresis and pathologically there was a polyneuropathy with preferential severe involvement of radial nerves. Flock incidence of the condition is low and previous experience suggests the clinical disorder is not progressive, recovery occurring at the end of lactation. The cause is unknown.

Neuraxial oedema of Hereford calves with and without hypomyelinogenesis.

The clinical and pathological features of 11 Hereford calves with neuraxial oedema with and without hypomyelinogenesis are described. Calves were affected at birth, recumbent and showed intermittent extensor spasm and hyperaesthesia. Nystagmus was noted in six cases. Pathologically, vacuolation of the central nervous system was seen in all cases. In two calves of horned Hereford stock this was restricted to white matter areas, while in the remaining calves of polled Hereford origin it was distributed in both white and grey matter. Hypomyelinogenesis was also a feature of this latter group of calves.

Skeletal abnormality of sheep: clinical radiological and pathological account of occurrence of dwarf lambs.

Details are given of the clinical, radiological and pathological appearance of dwarf lambs. Twenty-seven of 110 lambs born were affected, occurring as singletons, twins or one of a pair of twins. All affected lambs were dead within a few minutes of birth. They were short and plump with a domed head and shortened nose, short paddle-like limbs, a narrow thorax and swollen abdomen. The defect involved chondrocyte dysplasia, producing defective endochondral ossification and the presence of abnormal cartilage in the respiratory tract. No specific genetic or environmental cause was identified.

Bovine virus diarrhoea-mucosal disease virus-induced fetopathy in cattle: Efficacy of prophylactic maternal pre-exposure.

Maternal immunity was produced in Jersey heifers by exposing them to bovine virus diarrhoea-mucosal disease virus before conception. In the following pregnancy this immunity protected the fetuses from transplacental infection arising from challenge of the dams at 100 days gestation with homologous virus. Unprotected Jersey heifers showed a high incidence of death and fetal intrauterine growth retardation associated with transplacental viral infection. Functional normality of the locomotor system was assessed retrospectively from ciné films of each calf after birth, and scored for each of an overlapping series of clinical signs. The progeny of non-immune dams scored significantly lower than calves from the vaccinated heifers.

Bovine virus diarrhoea-mucosal disease virus: pathogenicity for the fetal calf following maternal infection.

Fifteen pregnant, bovine virus diarrhoea-mucosal disease (BVD-MD) antibody-free Jersey heifers were infected experimentally with a mixture of 10 cytopathic strains of BVD-MD virus isolated from cattle in Britain. Each cow was inoculated intramuscularly on gestation day 100 with a high or a low dose of virus grown in primary calf testis tissue cultures. None of the cows showed clinical signs of illness following exposure, but all had seroconverted within six weeks. Six fetuses, including one set of twins, died in utero following infection. Of these five were aborted between days 136 and 154; the sixth one was mummified and still retained at day 300. The remaining 10 fetuses survived to term, but all showed evidence of intrauterine growth retardation with or without gross malformation and/or dysmyelination of the central nervous system. Three were clinically affected with congenital nervous disease. Of the 10 liveborn fetuses, two had specific serum antibodies to BVD-MD. Non-cytopathic BVD-MD virus was recovered from all of the remaining eight. When non-immune cows become infected with BVD-MD virus in mid gestation: transplacental infection of the fetus will probably result; apart from the risk of fetal death, with or without abortion, there is a high probability of fetal mal-development which may not always be clinically obvious; the immunological competence of the fetus may be impaired; congenital infection is likely in a substantial proportion of liveborn calves. About one in 16 bovine fetuses in British herds are estimated to be at risk from BVD-MD virus infection.