Sclerosis In Animals Research Articles

Documented neurological diseases in camelids

Neurological disease has a wide range of causes in llamas and alpacas, but is most often related to infectious (viral or bacterial), metabolic, toxic and traumatic causes. As a consequence, the neurological manifestation of a systemic illness has to be differentiated from conditions that principally affect the peripheral or central nervous system. Subtle differences in the clinical manifestation and pathophysiology of neurological diseases do exist between camelids and other species. However, diagnostic tools similar to those used in other species are often essential to establish an etiological diagnosis. For example, while spinal radiography may be sufficient to identify traumatic conditions and bony lysis or sclerosis in animals with advanced degenerative vertebral disease, computed tomography or magnetic resonance imaging may be required to better evaluate patients with subtle changes.

Development of Postinfection Epilepsy After Theiler's Virus Infection of C57BL/6 Mice

Viral infection of the central nervous system can lead to long-term neurologic defects, including increased risk for the development of epilepsy. We describe the development of the first mouse model of viral-induced epilepsy after intracerebral infection with Theiler's murine encephalomyelitis virus. Mice were monitored with long-term video-electroencephalogram at multiple time points after infection. Most mice exhibited short-term symptomatic seizures within 3 to 7 days of infection. This was followed by a distinct latent period in which no seizures were observed. Prolonged video-electroencephalogram recordings at 2, 4, and 7 months after the initial infection revealed that a significant proportion of the mice developed profound, spontaneous epileptic seizures. Neuropathologic examination revealed hippocampal sclerosis in animals with epilepsy. Theiler's murine encephalomyelitis virus-infected C57BL/6 mice represent a novel "hit-and-run" model to investigate mechanisms underlying viral-induced short-term symptomatic seizures, epileptogenesis, and epilepsy. Importantly, this model will also be useful to investigate novel therapies for the treatment and prevention of epilepsy.

Apoptosis and necrosis induced in different hippocampal neuron populations by repetitive perforant path stimulation in the rat.

Patients experiencing spontaneous seizures of temporal lobe origin often exhibit a shrunken hippocampus, which results from the loss of dentate granule cells, hilar neurons, and hippocampal pyramidal cells. Although experimental attempts to replicate the human pattern of hippocampal sclerosis in animals indicate that prolonged seizures cause prominent injury to dentate hilar neurons and hippocampal pyramidal cells, dentate granule cells of animals are generally regarded as relatively resistant to seizure-induced injury. By evaluating pathology shortly after hippocampal seizure discharges were induced electrically, we discovered that some granule cells are highly vulnerable to prolonged excitation and that they exhibit acute degenerative features distinct from those of other vulnerable cell populations. Intermittent perforant path stimulation for 24 hours induced acute degeneration of dentate granule cells, dentate hilar neurons, and hippocampal pyramidal cells. However, stimulation for 8 hours, which was insufficient to injure hilar neurons and hippocampal pyramidal cells, was nonetheless sufficient to induce bilateral granule cell degeneration. Degenerating granule cells were consistently more numerous in the infrapyramidal than the suprapyramidal blade, and were consistently more numerous in the rostral than caudal dentate gyrus. Depending on the nature of the insult, acutely degenerating neurons exhibit distinct morphological features that are classifiable as either apoptosis or necrosis, although the degree of possible overlap is unknown. Light and electron microscopic analysis of the acute pathology caused by prolonged afferent stimulation revealed that degenerating hilar neurons and pyramidal cells exhibited the morphological features of necrosis, which is characterized in part by early cytoplasmic vacuolization before nuclear changes occur. However, acutely degenerating granule cells exhibited the clearly distinct morphological features of apoptosis, which include an early coalescence of nuclear chromatin into multiple nuclear bodies, compaction of the cytoplasm, cell shrinkage, and budding-off of 'apoptotic bodies' that are engulfed by glia. Whereas pyramidal cell debris persisted for months, granule cell debris disappeared rapidly. This observation may explain why significant granule cell vulnerability has not been described previously. These data document for the first time that dentate granule cells are among the cell types most vulnerable to seizure-induced injury, and demonstrate that whereas hilar neurons and pyramidal cells undergo a typically necrotic degenerative process, granule cells simultaneously exhibit morphological features that more closely resemble the degenerative process of apoptosis. This finding implies that the type of cell death induced by excessive excitation may be determined postsynaptically by the way in which different target cells 'interpret' an excitatory insult. This experimental model may be useful for identifying the biochemical mechanisms that initiate and mediate neuronal apoptosis and necrosis, and for developing strategies to prevent or induce these presumably distinct forms of neuronal death.