Biomedical subjects

Y Olsson

Publications and source records attributed to Y Olsson.

At least 145 records · Page 8Linked to original sources

PubMed1985

The temporal evolution of hypoglycemic brain damage. I. Light- and electron-microscopic findings in the rat cerebral cortex.

In the course of a study on the pathogenesis of neuronal necrosis in severe hypoglycemia, the morphological characteristics reflecting reversible and irreversible neuronal lesions were examined as a function of time following normalization of blood glucose. To that end, closely spaced time intervals were studied in the rat cerebral cortex before, during, and up to 1 year after standardized pure hypoglycemic insults of 30 and 60 min of cerebral isoelectricity. Both the superficial and deep layers of the cerebral cortex showed dark and light neurons during and several hours after the insult. By electron microscopy (EM) the dark neurons were characterized by marked condensation of both karyoplasm and cytoplasm, with discernible, tightly packed cytoplasmic organelles. The light neurons displayed clustering of normal organelles around the nucleus with clearing of the peripheral cytoplasm. Some cells, both dark neurons and neurons of normal electron density, contained swollen mitochondria with fractured cristae. Light neurons disappeared from the cerebral cortex by 4 h of recovery. Some dark neurons in the superficial cortex and almost all in the deep cortex evolved through transitional forms into normal neurons by 6 h recovery. Another portion of the dark neurons in the superficial cortex became acidophilic between 4 and 12 h, and by EM they demonstrated karyorrhexis with stippled electron-dense chromatin. The plasma membrane was disrupted, the cytoplasm was composed of amorphous granular debris, and the mitochondria contained flocculent densities. These definitive indices of irreversible neuronal damage were seen as early as 4-8 h recovery. Subsequently, the acidophilic neurons were removed from the tissue, and gliosis ensued. Thus, even markedly hyperchromatic "dark" neurons are compatible with survival of the cell, as are neurons with conspicuous mitochondrial swelling. Definite nerve cell death is verified as the appearance of acidophilic neurons at which stage extensive damage to mitochondria is already seen in the form of flocculent densities, and cell membranes are ruptured. Our previous results have shown that hypoglycemic neocortical damage affects the superficial laminae, chiefly layer 2. The present results demonstrate that, following the primary insult, this damage evolves relatively rapidly within the first 4-12 h. We have obtained no evidence that additional necrotic neurons are recruited after longer recovery periods.

Animals↗

PubMed1985

The temporal evolution of hypoglycemic brain damage. II. Light- and electron-microscopic findings in the hippocampal gyrus and subiculum of the rat.

Part I of this paper has documented the evolution of dark neurons into acidophilic neurons in the superficial laminae as well as the reversion of dark neurons to normal neurons in the deep laminae of the cerebral cortex in hypoglycemic brain damage. The present study describes the temporal evolution of hypoglycemic brain damage in the hippocampus. The evolution of dark neurons to acidophilic neurons was confirmed in this brain region. Four additional problems were addressed: Firstly, delayed neuronal death was looked for, and was found to occur in areas of CA1 undergoing mild damage. However, it was not preceded by a morphological free interval, had ultrastructural characteristics distinct from delayed neuronal death in ischemia, and hence should be considered a distinct phenomenon. Secondly, the gradient in the density of neuronal necrosis in the rat hippocampal pyramidal cell band was exploited to test the hypothesis that a more severe insult causes a more rapid evolution of neuronal changes. This was found to be the case, with a temporal spectrum in the timing of neuronal death: Necrosis occurred already after 2 h medially in the subiculum, and was delayed by up to several weeks laterally in CA1. Thirdly, the almost universal sparing of CA3 pyramidal neurons after 30 min hypoglycemic isoelectricity was exploited to address the question of whether reactive changes, which could with certainty be deemed reversible, occur in CA3. Mitochondrial injury was seen in these cells, and was found to be recoverable. No reactive changes of the type previously described following ischemic insults were observed. Fourthly, the astrocytic and vascular response of the tissue was studied. A sequence of astrocytic changes representing structural and probably metabolic activation of astrocytes was seen, consisting of morphological indices of increased turnover of cellular components. Capillaries demonstrated endothelial pits, vesicles, and prominent microvilli hours to days after recovery. The results demonstrate that, in the hippocampal gyrus as in other brain regions, hypoglycemic brain damage is distinct from ischemic brain damage and likely has a different pathogenesis.

Animals↗

PubMed1985

Neuron-specific enolase as a marker for intestinal neurons. An immunocytochemical study of the human intestinal tract.

Surgical specimens from various parts of the human intestinal tract as well as suction biopsy specimens, including mucosa and submucosa of the rectum, were fixed in formalin and embedded in paraffin by routine procedures. The distribution of immunoreactive areas indicating the presence of neuron-specific enolase (NSE) was then determined by using a sheep anti-human-NSE antiserum prepared in our laboratory. The immunocytochemical method revealed, in distinct contrast to other tissue components, the cell bodies of ganglion cells in the submucosa (Meissner's plexus) and in the muscle layers (Auerbach's plexus). The nerve bundles of the submucosa, of the muscle layers, and of the subserosal connective tissue were also stained, whereas the thin nerve processes of the mucosa were identified only rarely. The smooth muscle cells were stained weakly, but this reaction did not interfere with the identification of the neurons and their processes. Immunocytochemical demonstration of NSE is obviously a valuable additional method for visualization of the intrinsic intestinal innervation. It might well be that this technique will be of advantage in the diagnosis of pathologic processes, such as those occurring in Hirschsprung's disease and allied conditions.

Adolescent↗

PubMed1985

Cytofluorescence localization of ethidium bromide in the nervous system of the mouse. I. Ethidium bromide: its distribution in regions within and without the blood-brain barrier after intravenous injection.

A direct fluorescence-microscopic technique was effected to determine in the central nervous system (CNS) of the mouse the distribution of ethidium bromide after intravenous (i.v.) injection. The compound was visualized in thin cryostat sections of the brain fixed by vascular perfusion through the heart with a 10% buffered formalin solution. Ethidium bromide emitted a bright red fluorescent light in model experiments. The compound could not be detected in the vessel walls or brain parenchyma of the cerebral gray and white matters after i.v. injection indicating the presence of a blood-brain barrier (BBB) phenomenon to this compound. Signs of extravasation of ethidium bromide were present in the choroid plexus, the postremal area, the Gasserian ganglion, and in the circumventricular organs of the brain (neurohypophysis, organum vasculosum lamina terminalis, and median eminence) 3 min after the i.v. injection. Intense fluorescence was present in the nucleus and the cytoplasm of the cells in these areas, located outside of the BBB. Fluorescence had disappeared 24 h after the injection. Unexpectedly, red fluorescent material was seen in the parenchyma of the olfactory lobes of some animals, indicating, possibly, the presence of ethidium bromide. Ethidium bromide is known to suppress RNA, DNA, and protein synthesis in mammalian cells and has been used previously in neuropathology for studies on myelin lesions after injury to oligodendroglial cells. It can now, by a simple fluorescence-microscopic method, be traced directly in fixed tissue. Correlations can therefore be made between localization of the compound and its cytotoxic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1985

Cerebrovascular lesions in stroke-prone spontaneously hypertensive rats.

The cerebrovascular lesions of severe chronic hypertension were studied by light microscopy in perfusion-fixed, subserially sectioned brains from stroke-prone spontaneously hypertensive rats (SHRSP). The leakage and spread of plasma proteins were visualized by immunohistochemical detection of extravasated fibrinogen and by using an exogenous marker (Evans blue injected i.v.) for blood-brain barrier (BBB) dysfunction. In most SHRSP the hypertension did not lead to major BBB lesions in spite of a mean arterial pressure around 200 mm Hg at 6-9 months of age. Multifocal BBB damage occurred in a minor group of SHRSP, particularly within the cortex and the deep gray matter. A close spatial correlation was found between the leakage-spread of plasma constituents and the neuropathologic alterations. Fibrinoid degeneration of penetrating arterioles was found within the leakage sites. The surrounding gray matter showed petechial hemorrhages and abundant proteinaceous exudates rich in antifibrinogen-positive material. The current leakage of Evans blue and wide spread of fibrinoid substances suggested long-lasting damage to the BBB. Most neurons within the edematous gray matter had well preserved nuclei surrounded by a rim of cytoplasm with ill-defined outline as if vacuolation or lysis of the peripheral cytoplasm had occurred. The sponginess of the tissue progressed in severe cases to formation of necrotic cysts. Condensed acidophilic neurons were seen in the border zone between the edematous and more compact gray matter. The appearance and distribution of the gray matter lesions deviated in many respects from those commonly seen in regional ischemic infarcts. The fibrin thrombi found close to the cysts might be regarded as secondary events. The extensive spread of antifibrinogen-positive material within the white matter seemed to originate mainly from the chronic leakage sites in the gray matter. Increased number of large astrocytes were seen within the leakage sites and along the spreading pathways for the edema constituents. The white matter showed a rarefied texture with widely dispersed nerve fiber tracts, volume expansion, and occasional cyst formation. The results indicate a crucial pathophysiologic role for the egress, spread, and accumulation of vasogenic edema in the development of the cerebrovascular lesions in SHRSP.

Animals↗

PubMed1985

Cytofluorescence localization of propidium iodide injected intravenously into the nervous system of the mouse.

Propidium iodide, like its analogue ethidium bromide, is a compound which can be used as a marker of nucleic acids. This substance emits a red fluorescent light after exposure to UV light and has therefore been used previously as a nuclear stain in immunofluorescence studies and in flow cytometry. The present experiments were carried out to find out if propidium iodide could be traced in sections of the nervous system after i.v. injections. Due to the general toxicity of the compound detectable amounts of propidium iodide could not be obtained by a single i.v. injection. However, multiple injections of small amounts (0.1 mg) over a period from 15 min to 8 h (total dose 0.7-1.0 mg) were tolerated without any signs of adverse effects. In such experiments propidium iodide did not extravasate into the cerebral gray or white matter, i.e., areas of the brain located within the blood-brain barrier (BBB). On the other hand, the compound spread into the choroid plexus, the circumventricular organs, the Gasserian ganglion, and sciatic nerve, i.e., regions located outside the BBB. It had a strong tendency to label the nucleus and the perikaryon of the cells in each of these territories. Perifascicular injection of propidium iodide around the sciatic nerve was followed by a marked cellular uptake not only in the epineurium but also in the endoneurium. The shape and position of the labeled nuclei strongly indicated that they were the nuclei of Schwann cells. Previous studies have shown that propidium iodide can be used as a retrograde tracer in neuroanatomic research.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Topographical localization of motor endplates in cryosections of whole human muscles.

The distribution of motor endplates in biceps brachii, tibialis anterior, and sartorius muscles from human adults was studied by staining longitudinal cryosections of whole muscle for cholinesterase. A special freezing technique was used to prevent the muscle from cracking before sectioning on a heavy cryostat microtome. The results from a large number of cryosections from biceps brachii and tibialis anterior muscles were analyzed by a computer and the topographical distributions of endplates in different views of the muscles were reconstructed. In the biceps brachii muscle, the endplates formed a fairly distinct, slightly V-shaped band through the middle of the two heads. In the tibialis anterior muscle, the majority of the endplates were superficially distributed along the whole muscle. In the longitudinal sections from the middle part of the muscle, they gave the pattern of a parabola with its apex at the proximal end of the muscle. In the sartorius muscle, the endplates were scattered throughout the muscle and no endplate band was observed. The findings are in accordance with results obtained 30 years ago in investigations of muscle from small children and stillborn infants.

Adult↗

PubMed1984

Neuromuscular involvement in primary hyperparathyroidism.

Sixteen consecutive patients with primary hyperparathyroidism (HPT) were examined by a combination of electrophysiological, morphological and biochemical measurements. Six patients had, preoperatively, subjective impairment of neuromuscular function. Three of them were improved by the normalization of parathyroid function after surgery. In the other patients, who either had vague symptoms or appeared to be asymptomatic, the operation did not cause subjective changes in their neuromuscular function during a 3-month follow-up period. Altogether seven patients, three of whom had symptoms, had impairment of the neuromuscular transmission as evaluated by the single-fibre EMG technique. The changes were of slight degree and unlikely to be of clinical importance. Two patients had a slightly reduced nerve conduction velocity and in two cases moderate abnormalities were found in muscle biopsy specimens. In conclusion, the muscular weakness reported by HPT patients did not seem to be caused by disturbance of neuromuscular transmission. HPT patients who preoperatively were apparently asymptomatic did not have defects of their neuromuscular transmission that were of clinical significance.

Aged↗

PubMed1984

The distribution of hypoglycemic brain damage.

Rats were exposed to insulin-induced hypoglycemia resulting in periods of cerebral isoelectricity ranging from 10 to 60 min. After recovery with glucose, they were allowed to wake up and survive for 1 week. Control rats were recovered at the stage of EEG slowing. After sub-serial sectioning, the number and distribution of dying neurons was assessed in each brain region. Acid fuchsin was found to stain moribund neurons a brilliant red. Brains from control rats showed no dying neurons. From 10 to 60 min of cerebral isoelectricity, the number of dying neurons per brain correlated positively with the number of minutes of cerebral isoelectricity up to the maximum examined period of 60 min. Neuronal necrosis was found in the major brain regions vulnerable to several different insults. However, within each region the damage was not distributed as observed in ischemia. A superficial to deep gradient in the density of neuronal necrosis was seen in the cerebral cortex. More severe damage revealed a gradient in relation to the subjacent white matter as well. The caudatoputamen was involved more heavily near the white matter, and in more severely affected animals near the angle of the lateral ventricle. The hippocampus showed dense neuronal necrosis at the crest of the dentate gyrus and a gradient of increasing selective neuronal necrosis medially in CA1. The CA3 zone, while relatively resistant, showed neuronal necrosis in relation to the lateral ventricle in animals with hydrocephalus. Sharp demarcations between normal and damaged neuropil were found in the hippocampus. The periventricular amygdaloid nuclei showed damage closest to the lateral ventricles. The cerebellum was affected first near the foramina of Luschka, with damage occurring over the hemispheres in more severely affected animals. Purkinje cells were affected first, but basket cells were damaged as well. Rare necrotic neurons were seen in brain stem nuclei. The spinal cord showed necrosis of neurons in all areas of the gray matter. Infarction was not seen in this study. The possibility is discussed that a neurotoxic substance borne in the tissue fluid and cerebrospinal fluid (CSF) contributes to the pathogenesis of neuronal necrosis in hypoglycemic brain damage.

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PubMed1984

Distribution of exudated FITC-dextrans in experimental vasogenic brain edema produced by a focal cryogenic injury.

Mice were subjected to cortical cryogenic brain injury, and FITC-dextrans (mol. wt. 20,000 or 150,000) were injected intravenously (i.v.). After a survival period of 4 h the distribution of the FITC-dextrans was determined by a histotechnical procedure described recently ( Hultstr öm et al. 1982a ). This technique is based on freeze-drying and vapor fixation to immobilize the tracer and to provide tissue fixation. In and around the cryogenic injury both tracers leaked out of the cortical and the leptomeningeal vessels and spread into the brain parenchyma. They were seen as multiple, closely apposed droplets of fluorescent material best recognized by fluorescence microscopy under high magnification. The tracers were also taken up by neuronal perikarya and in glial cell nuclei of, presumably, astrocytic origin. Our study shows that the FITC-dextran technique can be used for experimental studies on the vasogenic form of brain edema. The patterns formed by the extravasated tracers have qualitative similarities to those produced by other more commonly used tracers, such as fluorochrome-labeled serum proteins and peroxidase.

Animals↗

PubMed1984

Fluorescence-microscopic localization of in vivo injected ethidium bromide in the nervous system of the mouse.

Ethidium bromide is a compound which can suppress DNA, RNA, and protein synthesis in mammalian cells. It is a very useful tool in experimental neuropathology for studies on myelin lesions taking place in the spinal cord after injury to oligodendroglial cells following intracisternal or intraspinal administration. By using a technique described in this short original communication we can now directly trace the distribution of the compound in various cells of the central and the peripheral nervous systems after its administration to a living experimental animal. Therefore, in the future direct correlations can be made between the cellular distribution of the compound and its cytotoxic effects.

Animals↗

PubMed1984

Metabolic, circulatory, and structural alterations in the rat brain induced by sustained pentylenetetrazole seizures.

Previous studies have demonstrated that bicuculline-induced seizures of 1-2 h in duration lead to structural, metabolic, and circulatory alterations in the rat brain. Such alterations were observed even though cerebral oxygenation seemed adequate. In the present study, we explored whether pentylenetetrazole, a convulsant which interferes with gamma-aminobutyric acid inhibition by mechanisms other than that of bicuculline, leads to similar structural alterations and to similar cerebral metabolic and circulatory changes. The drug was given to paralyzed and artificially ventilated rats in a dose of 100 mg/kg i.v., and seizures were allowed to continue for 1-120 min. The onset of seizures was accompanied by a small perturbation of cerebral cortical energy state, but sustained changes were confined to decreases in phosphocreatine, glycogen, and glucose and increases in lactate, pyruvate, and cyclic nucleotides. A sustained increase in free fatty acid concentration was observed, with the largest change occurring in arachidonic acid concentration. In the cerebellum, metabolic perturbation was clearly less pronounced, but cyclic nucleotide concentrations rose substantially. Local cerebral blood flow increased in all but two structures (frontal cortex and caudoputamen), but pronounced interstructural changes occurred. Nerve cell changes and astrocytic swelling were observed in the cerebral cortex. There was marked status spongiosus due to edema, which was mainly astrocytic and most prominent in cortical layer 3 and in parts of hippocampus. Nerve cell changes were of two basic types. The type 1 injured neurons, condensed and triangular in shape, were mainly confined to the edematous areas. Many of them had cytoplasmic vacuoles which on electron microscopy proved to be mainly dilated Golgi cisternae or mitochondria. As compared with bicuculline-induced epilepsy such abnormal mitochondria appeared to be more frequent. The type 2 neurons had slit-formed intracytoplasmic and perinuclear vacuoles resulting from dilatation of the endoplasmic reticulum cisternae and the nuclear envelope. The cerebellum looked normal by light microscopy. We conclude that, in the rat, sustained seizure activity induced by pentylenetetrazole is accompanied by alterations in EEG activity, in cerebral metabolism and circulation, and in cell structure similar to those elicited by bicuculline.

Animals↗

PubMed1984

Vascular permeability in acute triethyltin-induced brain edema studied with FITC-dextrans, sodium fluorescein and horseradish peroxidase as tracers.

In golden hamsters, a study was made on the vascular permeability changes which might take place during the formation of triethyltin (TET)-induced brain edema. For this purpose, the animals received a single intravenous (i.v.) injection of TET sulphate (5-10 mg/kg b.wt) and groups of animals were studied 4 to 24 h thereafter. By the use of a new density gradient technique based on polyvinylcoated silica particles (1), it was shown that white matter edema was present already at 4 h after the TET injection. The edema then progressed during the following 20 h. Electron microscopy revealed that fluid accumulated in myelin vacuoles of the hamsters in the same way as has been described in other animal species. The macromolecular tracer, horseradish peroxidase mol.wt 40,000 injected i.v., did not leak out of the cerebral vessels during the period when edema developed. In order to find out if the formation of edema is associated with a vascular permeability increase to other and smaller markers, we used several fractions of FITC-dextrans varying from mol.wt 3,000 to 70,000 and determined their intracerebral localization with a histotechnical procedure. FITC-dextrans, mol.wt 70,000, did not leak out of the cerebral vessels in any of the TET intoxicated hamsters during the observation period of 24 h. The same was true for most animals given the other dextran fractions. However, FITC-dextrans, mol.wt 3,000-20,000 were present outside the vessels in the edematous optic nerves and corpus callosum in a few TET treated animals taken 16-24 h after the TET injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Hypoglycemic brain injury in the rat. Correlation of density of brain damage with the EEG isoelectric time: a quantitative study.

Thirty-eight male Wistar rats were exposed to insulin-induced hypoglycemia resulting in periods of cerebral isoelectricity ranging from 10 to 60 min. Plasma glucose levels during cerebral isoelectricity ranged from 0.12 mM to 1.36 mM. Control rats were injected with insulin, but hypoglycemia was terminated with glucose at the stage of large delta-wave EEG slowing. After recovery, the rats were allowed to wake up and survive for 1 wk. The number of dying neurons was assessed with acid-fuchsin/cresyl-violet-stained, whole-brain, subserial sections using direct visual counting of acidophilic, cytoclastic neurons. Brains from control rats that were not allowed to become isoelectric showed no dying neurons. Ten minutes of cerebral isoelectricity produced very minimal brain damage. The density of neuronal necrosis was positively related to the number of minutes of cerebral isoelectricity up to the maximum examined period of 60 min, but showed no correlation with the blood sugar levels. The cerebral cortex, hippocampus, caudate nucleus, spinal cord, and, to a lesser extent, cerebellar Purkinje cells were affected. The distribution of neuronal necrosis was not identical with that seen in ischemia, but, rather, suggested a CSF-borne neurotoxin operant in contributing to the pathogenesis of neuronal necrosis in hypoglycemic brain damage. Neuronal death does not occur in hypoglycemia unless the EEG becomes isoelectric, whatever the blood sugar level. Serious brain damage does not occur until electrocerebral silence has been established for at least several minutes. Neuronal death accelerates after 30 min of EEG isoelectricity in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Cytotoxic effects of adriamycin on the central nervous system of the mouse--cytofluorescence and electron-microscopic observations after various modes of administration.

Adriamycin (doxorubicin) is commonly used in the treatment of malignant tumours. Adverse effects on the CNS have not been described so far, but the patients may suffer from a dose-related myocardial toxicity. Lesions have previously been observed in peripheral ganglia of experimental animals. Using a direct fluorescence microscopic method we have investigated the distribution of adriamycin in the CNS of normal mice after various modes of administration. Adriamycin, after intravenous (i.v.) injection, did not pass into the brain generally but entered the choroid plexus and circumventricular organs, namely the median eminence, postremal area, subfornical organ, organum vasculosum of the lamina terminalis, pineal gland, and neurophypophysis. After a single i.v. injection of the drug, the animals showed distinct morphological changes in three regions examined thus far, the neurohypophysis (NH), median eminence (ME), and postremal area (PA). In the NH and ME many degenerated neurosecretory axon terminals were observed. In addition, nuclear and cytoplasmic changes were seen in the pituicytes and glial cells of the ME. The PA showed severe neuronal alterations which included nucleolar segregation, rarefaction of the nuclear chromatin, and cytoplasmic changes. When the blood-brain barrier was circumvented by direct microinjection into the cerebral ventricles, the drug passed into the surrounding brain parenchyma, being detected in the nuclei of both neurons and glia. It can therefore be assumed that, when adriamycin is given to patients with a disturbance of the blood-brain barrier, the drug may spread into the brain in the same way. The blood-brain barrier can also be bypassed by injecting a substance intramuscularly or/and intradermally and letting it pass into the spinal cord or brain-stem by retrograde axonal transport. In model experiments, adriamycin was injected into the tongue and six hours later its fluorescence could be detected in the hypoglossal neurons. Animals allowed to survive for a longer period, showed selective damage to these neurons as evidenced by early nuclear changes followed by alterations in the cytoplasm.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1983

Bicuculline-induced epileptic brain injury. Transient and persistent cell changes in rat cerebral cortex in the early recovery period.

It was earlier shown that bicuculline-induced status epilepticus gives rise to profound acute changes in the rat cerebral cortex, i.e. edema and neuronal alterations. In the present study, we explored to what extent interruption of the seizure activity reverses the changes observed. To that end, status epilepticus of 1 and 2h duration was induced by bicuculline before the seizures were arrested by i.v. injection of diazepam. The brain was then fixed by vascular perfusion either 5 min (1 h of seizures) or 2h (1 and 2h of seizures) of recovery and cerebral cortical tissue was studied by light (LM) and electron microscopy (EM). Already 5 min following the arrest of seizure activity most of the astrocytic edema had disappeared, and the 2h of recovery, following 1 h of status epilepticus, the edema was virtually absent, and only few injured cells were found (only about 1% of the neuronal population). When recovery was instituted after 2 h of status epilepticus, numerous dark, triangular neurons were found. In the last group an adequate blood pressure could not be obtained. Therefore, the cellular alterations observed were probably not the result of the seizure activity per se. After 5 min of recovery, Em studies showed condensed, dark-staining injured neurons, similar to those previously observed in non-recovery animals. However, an increased incidence of swollen mitochondria was observed. After 2 h of recovery a few severely injured neurons remained which showed signs of progressive injury with fragmentation of the cell body.

Animals↗

PubMed1983

Influence of systemic factors on experimental epileptic brain injury. Structural changes accompanying bicuculline-induced seizures in rats following manipulations of tissue oxygenation or alpha-tocopherol levels.

A previous study from the laboratory showed that status epilepticus induced by bicuculline administration to ventilated rats produced astrocytic swelling and nerve cell changes ("type 1 and 2 injury") particularly in layers 3 and 5 of the neocortex (Söderfeldt et al. 1981). The type 1 injured neurons were characterized by condensation of cyto- and karyoplasm and the less common type 2 cells were characterized by swelling of endoplasmic reticulum including the nuclear envelope. In the present study we explored whether changes in cerebral oxygen availability altered the extent or character of the cellular alterations. Animals with 2 h of status epilepticus were made either hyperoxic (administration of 100% O2), hypoxic (arterial pO2 50 mm Hg) or hypotensive (arterial blood pressure of either 70-75 or 50 mm Hg). Furthermore, we explored whether "oxidative" damage occurred by manipulating tissue levels of alpha-tocopherol, a known free radical scavenger. Non-epileptic control animals exposed to comparable degrees of hypoxia or hypotension showed no or minimal structural alterations. In the epileptic animals the results were as follows. Hyperoxia did not change the quality or extent of the structural alterations previously observed in normoxic epileptic animals. Neither administration nor deficiency of vitamin E did modify this pattern of alterations. In hypoxia the extent of cell damage was the same or somewhat larger than in normoxic, epileptic animals. In addition, neurons often showed cytoplasmic microvacuoles due to swelling of mitochondria. The hypoxic animals also showed swelling of astrocytic nuclei with clumped chromatin. Changes similar to those observed in hypoxic animals also appeared in moderate hypotension (mean arterial blood pressure 50 mm Hg), whereas mild hypotension (70-75 mm Hg) did not change the character of the tissue injury from that seen in hyperoxic or normoxic epileptic rats. The present results demonstrate that the neuronal cell damage that can be observed when the brain is fixed by perfusion after status epilepticus of 2 h duration is not exaggerated by hyperoxia or vitamin E deficiency nor is it ameliorated by a moderate restriction in cerebral oxygen supply or by vitamin E administration. If anything, hypoxia (or moderate hypotension) appears to increase the extent of damage and it clearly alters its ultrastructural characteristics. However, although the results fail to support the notion that epileptic cell damage is "oxidative", definite conclusions must await information on the cell damage that remains upon arrest of the epileptic activity.

Animals↗

PubMed1983

Cytofluorescence localization of adriamycin in the nervous system. IV. cellular uptake of the drug in peripheral nerve following various modes of injection to bypass the blood-nerve and the perifascicular barriers.

Adriamycin (Doxorubicin) is a powerful anthracyclic compound, which is widely used in the treatment of malignant diseases. In the rat a single systemic injection of the drug can induce pronounced lesions in peripheral ganglia, whereas in other parts of the peripheral nervous system (PNS) no changes have been reported. Since adriamycin can be directly traced in tissue sections by fluorescence microscopy it is very well suited for experimental studies on the relation between cytotoxic effects and distribution of the drug following various modes of administration. We have previously shown that after an intravenous (i.v.) injection there is an absence of adriamycin-induced nuclear fluorescence in the endoneurium of mouse sciatic nerve (Bigotte et al. 1982 b). This could either be due to barrier effects in endoneurial vessels and the perineurium or to a lacking capacity of the endoneurial cell population to take up and retain adriamycin. In the present study the blood-nerve and the perifascicular diffusion barriers were therefore bypassed by endoneurial microinjections of adriamycin. After this mode of administration, Schwann cells, endoneurial mast cells, endothelial cells, and pericytes became labeled. Experimental damage of these barriers induced by ligation of the nerve also resulted in a diffusion of the drug into the endoneurial area and labeling of the same cells. The absence of nuclear binding in the endoneurium of mouse sciatic nerves after i.v. injection of adriamycin is therefore most probably due to a low or absent passage of the drug from the blood into the endoneurium, i.e., a combined barrier action of endoneurial vessels and the perineurium. Other experiments with epineurial application of the drug showed that thin intramuscular (i.m.) nerve branches differ from the sciatic nerve fascicles in allowing small amounts of adriamycin to enter the endoneurium. The present observations are of interest since it can be assumed that patients receiving adriamycin as a cytostatic drug may suffer nerve lesions whenever defects of nerve barriers are present.

Animals↗