Henryk M. Wiśniewski

Experimental Production of Neurofibrillary DegenerationI. Light Microscopic Observations

1. Intracerebral or intratheeal administration of alum phosphate in rabbits resulted in the development of convulsive seizures, as well as of characteristic neuronal changes throughout the CNS. 2. The neuronal change consisted in a hydropic alteration of the cytoplasm and in a conspicuous neurofibrillary degeneration. 3. Chemical analysis of brain obtained from animals sacrificed during the terminal convulsive state demonstrated significant decreases in brain water and chloride space, and a relatively large increase in the thiocyanate space. 4. The effect of alum phosphate which is described may provide an experimental model for further investigations of the morphological substrate of epileptic neuronal activity, as well as of the pathomechanism of neurofibrillary degeneration.

Ultrastructural studies of the dying-back process 1. Peripheral nerve terminal and axon degeneration in systemic acrylamide intoxication

The spatio-temporal pattern of distal peripheral nerve, sensory and motor nerve terminal, degeneration in experimental acrylamide neuropathy has been examined. Tissue was sampled from limbs of cats throughout various stages of intoxication (e.g. 7–32 days of 10 mg/kg/day and up to 294 days of 3 mg/kg/day of acrylamide) and examined by light and electron microscopy. Nerve terminals of a few Pacinian corpuscles in hindfoot and forefoot toepads displayed the first abnormalities, before the onset of clinical signs; filopod axon processes were lost, axolemmas disappeared and axoplasm was phagocytosed by inner core cells. Degeneration of adjacent primary annulospiral endings of muscle spindles in hindfoot muscle began shortly after the first changes in Pacinian corpuscle axons. Later, juxtaposed secondary muscle spindle endings and motor nerve terminals, supplying nearby extrafusal muscle fibers, began to degenerate. These sensory and motor nerve terminals accumulated neurofilaments, became swollen and disappeared. Contemporaneous with the early degenerative changes in some nerve terminals, seattered preterminal nodes, and their paranodes, displayed focal axonal accumulations of neurofilaments, mitochondria and dense bodies. These organelle conglomerations were associated with focal axonal swelling and paranodal retraction of myelin. This axonal change appeared to spread along internodes and to lead to fiber degeneration with the formation of ovoids which were later replaced by bands of Büngner. Fiber degeneration proceeded proximally as intoxication progressed. Above the proximal limit of fiber breakdown, axons displayed progressively fewer abnormalities in the form of adaxonal Schwann cell ingrowths and swollen paranodal regions. The cardinal conclusions of this study of acrylamide neuropathy are: 1-some distal sensory nerve endings (Pacinian corpuscle and annulospiral terminals) in the hindfeet begin to degenerate before adjacent motor nerve terminals supplying extrafusal muscles, and 2− the distal tips of the largest and longest axons are not most vulnerable, although there is a propensity for long and large axons to die-back first. In view of these observations, the etiology of the dying-back process requires re-examination.

Neuritic (Senile) Plaques and Filamentous Changes in Aged Rhesus Monkeys

Three rhesus monkeys, whose approximate ages were 16 to 18 years old, and one 22 to 23 years old, were studied for age changes in the nervous system. The brains of all four were slightly shrunken and the meninges were fibrotic. The vessels were stiff and fibrosed, but were not atheromatous. The lateral ventricles were mildly dilated. Bodian preparations of the oldest monkey and of one of the 16− to 18-year-old monkeys revealed the presence of neuritic (senile) plaques. Serial one-micron toluidine blue-stained sections showed that some plaques were closely associated with capillaries. Electron microscopic studies revealed that the plaques were identical to those of human Alzheimers disease except that the typical twisted tubules were absent. Outside the plaques there were scattered neurites showing degeneration of the type found in the neuritic plaques. Furthermore, two forms of rare pathological fibrillar material were found in 3 animals. One was made up of pairs of helically wound 100 Å filaments with a twist every 500 Å. The other fibrillar structures were made up of bundles of parallel filamentous elements, each about 130 Å thick, with a distinctly granular structure on longitudinal section. A list of other abnormalities includes vascular amyloidosis, lipofuscin accumulation, dark neurons undergoing phagocytosis, myelin remodeling, aggregates of large electron-dense droplets, enlarged mitochondria and mitochondria with paracrystalline inclusions, corpora amylacea, Rosenthal fibers and two types of virus-like particles.

Morphology of the Aging Brain, Human and Animal

Publisher Summary This chapter reviews the pathological changes found in the brains of old humans and animals and discusses which of them should be considered responsible for the deterioration of function. Biopsy and autopsy material from patients with and without senile dementia and from younger people with the diagnosis of Alzheimers presenile dementia is included. The animal material consisted of five dogs, 15 to 18 years old, and four Rhesus monkeys aged 15 to 24 years. Most of the tissue comprised samples taken from frontal and hippocampal cortex. Even a superficial look at the life span of different animals indicates that there are some general phenomena that set a ceiling on the longevity of each animal species. One might consider that the aged cell is an environment in which certain pathological changes can readily develop. In conclusion, the morphological data indicate that studies of neuronal fibrous protein and synaptic pathology with special emphasis on mitochondria are the most urgent problems facing neuro-gerontologists.

Dynamics of Cold Injury Edema

Cold injury edema may serve as an experimental model for an edematous process in the brain tissue originating from an increased vascular permeability. Undoubtedly, this type of edema is of a paramount clinical importance as a dreaded complication of head injuries, brain tumors, inflammatory processes, etc.

Peripheral nerve ischemia. Part 1. Experimental model.

Abstract Following simultaneous ligation of the abdominal aorta and the femoral artery, extensive lesions were consistently produced in the nerves of the hind limb in the absence of gangrene in the ischemic leg. Total necrosis of all elements of nerve bundles was seen to involve most of the segment of tibial and peroneal nerves between the knee and the ankle. Distal portions of these nerves in the first days after vascular ligation appeared either morphologically normal or showed only minor changes. Later they underwent Wallerian degeneration. The morphologic features and dynamics of changes in the necrotic portion differed from the axonal degeneration seen in the more distal portions of the affected nerves. This model of peripheral nerve ischemia has two advantages in comparison to models used before, namely that: marked changes are produced in every cat, and there is no compression or stretching, or any manipulation of investigated nerves and thus there is no doubt that the changes are related to ischemia.

On the relationship of brain vasculature to production of neurological deficit and morphological changes following acute unilateral common carotid artery ligation in gerbils.

The known susceptibility of the Mongolian gerbil to cerebral infarction following unilateral carotid artery ligation has been attributed in the past to the demonstrated absences of an anastomotic supply between the anterior and posterior cerebral circulations. In a study of 34 adult gerbils exposed to such a procedure, 11, or 33%, developed severe neurological sequelae and succumbed to the procedure in less than 30 hr, whereas 23 animals survived with only minor or transient neurological signs. All animals displayed the expected lack of an anastomosis between the anterior and posterior circulations, but in addition the animals which survived the procedure were found to have a prominent early cross-connection between the anterior cerebral arteries, whereas the animals which succumbed had no such connection. Neuropathological changes in susceptible animals were apparent as early as 3 and one-half hr after ligation and consisted of edema, initially perivascular and then intraneuronal, slowed by acute necrosis. A variety of other vascular anomalies was encountered. We conclude that the peculiar susceptibility of Mongolian gerbils to cerebral infarction following acute unilateral common carotid artery ligation is not related primarily to lack o adequate collaterals between the anterior and the anterior cerebral arteries, but to the degree of adequate adequacy of communication between the anterior cerebral arteries. The critical difference may be more one of degree, i.e. the point at which the medial branches of the anterior cerebral artery fust to become anazygos vessel, rather than an actual difference in the pattern of distribution of the anterior cerebral arteries. The presence of other variation in vascular supply in a relatively small series suggests that results of similar studies of infarction and response to treatment be interpreted with caution.

Study on the propagation of Herpes simplex virus (type 2) into the brain after intraocular injection

Abstract Herpes simplex virus (type 2) was injected into the left eye of 6-week-old New Zealand albino rabbits. At varying time intervals thereafter samples were taken from the optic system for light and electron microscopic examination. Virus particles were found within the perikaryon of retinal ganglion cells and their axons, as well as within glia, 2 days after the inoculation. On the following day infected neurons and glial cells were found also in the contralateral, but not ipsilateral superior colliculus (SC) and lateral geniculate body (LGB). Since the optic nerve fibers are almost completely decussated in the chiasm, the findings is consistent with an intra-axonal spread of the virus in an anterograde direction from the perikarya of the retinal ganglion cells to the SC and LGB. The present experiment indicates also that while long distances within the nervous system are spanned by viruses by means of the axonal transport mechanism, simultaneously cell-to-cell infection takes place as well. Ultrastructurally, virus particles were found in the axons, located within vesicular or cisternal structures, which probably represent agranular endoplasmic reticulum. A possible role of the axonal endoplasmic reticulum for the transport of virus particles is pointed out.

Vesicular Disruption of Myelin in Autoimmune Demyelination

A pattern of autoimmune demyelination in EAE and EAN has been described which was encountered consistently and was sometimes more common than the better known phenomenon of active stripping of myelin by macrophages. This pattern involved the rapid dissolution of myelin into a vesicular network which was later degraded by macrophages. It occurred early in the disease, was not accentuated perivascularly, and was usually associated with the presence of macrophases. The underlying mechanisms are not known but several alternatives have been discussed, viz., activity of locally released antibody, cytotoxic factors, or hydrolytic enzymes.

Reduced number and altered morphology of microglial cells in colony stimulating factor-1-deficient osteopetrotic op/op mice

The numerical density of microglial cells is reduced by 47% in the corpus callosum, by 37% in the parietal cortex and by 34% in the frontal cortex of mice mutant at the op locus which are totally devoid of colony stimulating factor-1 (CSF-1), the major growth factor for macrophages. Moreover, microglia in the frontal cortex of the op/op mice are smaller and have shorter cytoplasmic processes compared to control mice. Study suggests that CSF-1 plays a role in vivo in the formation and maturation of microglia and has little or no effect on perivascular cells.