Biomedical subjects

Y Olsson

Publications and source records attributed to Y Olsson.

At least 127 records · Page 7Linked to original sources

PubMed1989

Regional cerebral blood flow and histopathologic changes after middle cerebral artery occlusion in rats.

Changes in regional cerebral blood flow were correlated with the distribution of histopathologic signs of brain injury in 35 rats after middle cerebral artery occlusion. Rats were allowed to survive for periods of up to 4 weeks after the operation, and we focused particular interest on the time course of blood flow changes from the initial ischemic events to the late stage of infarction. Regional blood flow was measured using [14C]iodoantipyrine and a quantitative autoradiographic technique. Blood flow in regions with histologic signs of infarction (i.e., the lateral caudoputamen and adjacent neocortex) was below 0.238 ml/g/min, corresponding to 15% of normal values for those regions. In perifocal regions without infarction such as the medial caudoputamen and globus pallidus, cerebral blood flow was also reduced, but it never declined below 20% of its normal value. The decrease in cerebral blood flow was most marked during the first hours after occlusion. Thereafter, cerebral blood flow values gradually normalized, and at 4 weeks there were no significant differences compared with the contralateral side. The border between cortical regions with hypoperfusion and normal cerebral blood flow was rather sharp in the coronal plane, but in the sagittal plane there was a more gradual transitional region. The region with hypoperfusion, observed in the sagittal plane, was most widespread in the acute stage, and normalization of flow occurred particularly from anterior and posterior cortical regions toward the ischemic focus. The possibility for penumbral conditions in the cortex thus exists, particularly in the anterior and posterior borders of the infarction, and remains for several hours after the initial insult.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

S-100 protein and neuron-specific enolase in CSF after experimental traumatic or focal ischemic brain damage.

Cerebrospinal fluid (CSF) markers of brain damage are potentially capable of providing quantitative information about the extent of certain neurological injury. The presence of such markers in CSF after brain damage is transient and it is essential to understand their kinetics if they are to be used in clinical practice. In the present study, the CSF concentrations of two neurospecific proteins. S-100 protein and neuron-specific enolase (NSE), were determined in rats before and repeatedly after one of two types of experimental brain damage: traumatic cortical injury and focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion. The two types of experimental brain damage resulted in significant differences in the kinetics of S-100 and NSE concentrations in CSF. Cortical contusion was followed by a rapid increase in both S-100 and NSE and a peak occurred in both after about 7 1/2 hours, at which time the values declined toward normal. A second, smaller peak was seen after about 1 1/2 days. The increase and decrease in S-100 and NSE levels in CSF was slower after MCA occlusion; a peak was seen after 2 to 4 days. Furthermore, S-100 was generally higher than NSE after trauma, whereas after MCA occlusion the NSE concentration was slightly higher than the S-100 value. These results support the use of CSF markers for estimation of the extent of brain damage in experimental models and forms a basis for the understanding of their kinetics, which is important for their use in clinical practice.

Animals↗

PubMed1988

A transient hypertensive opening of the blood-brain barrier can lead to brain damage. Extravasation of serum proteins and cellular changes in rats subjected to aortic compression.

A transient increase in blood pressure was induced in 15 male Sprague Dawley rats by clamping the upper abdominal aorta for 8-10 min. Three rats served as controls. The brains were fixed by perfusion 2 h or 7 days later. Evan's blue-albumin (EBA) was used for macroscopic evaluation of the blood-brain barrier (BBB) integrity. Extravasated plasma albumin, fibrinogen and fibronectin were demonstrated by immunohistochemistry on paraffin sections. Glial fibrillary acidic protein (GFAP) was visualized in the same way. Parallel sections were analyzed for possible parenchymal changes associated with the BBB breakdown. Multiple focal areas of BBB opening were seen in the brains of the three rats killed 2 h after the hypertensive episode. The plasma proteins were present in the vascular wall, extracellular space and within certain neurons. Shrunken acid fuchsin positive neurons were seen in some areas of extravasation. After 7 days, in 5 out of 12 rats a few local lesions with EBA leakage and positive immunostaining for plasma proteins were seen. Structurally these lesions were characterized by shrinkage, fuchsinophilia and disintegration of neurons and proliferation of astrocytes. Thus, a transient opening of the BBB by acute hypertension may lead to permanent tissue damage.

Acute Disease↗

PubMed1988

Cyst formation and glial response in the brain lesions of stroke-prone spontaneously hypertensive rats.

The brain lesions in spontaneously hypertensive stroke-prone rats (SHRSP) are characterised by multifocal microvascular damage, breakdown of the blood-brain barrier, massive extravasation of plasma constituents and severe brain oedema, with consequent spongy and cystic tissue destruction in the cerebral cortex and basal ganglia as well as loosening of the white matter. In this paper we analyse in greater detail the pathogenetic mechanisms by which the spongy and cystic lesions are formed and the response of astrocytic cells. For this purpose, tracer (Evans blue)-stained brain lesions were examined in 8-month-old SHRSP immunohistochemically and electron microscopically. Sponginess of the neuropil in small lesions and at the periphery of larger lesions was due to swollen neuronal and astrocytic cell processes, i.e. at this stage the oedema was mainly intracellular. Cystic lesions were formed in the grey matter both by expansion of the extracellular space (ECS) containing protein-rich oedema fluid, and by rupture and subsequent loss of massively swollen cellular elements. In the white matter small slit-formed cysts along the fibre tracts were also formed by the expansion of ECS. In apparently recent lesions astrocytes displayed cyto-plasmic oedema but otherwise were still fairly normal. In more chronic lesions increased numbers of enlarged astrocytes with prominent staining for glial fibrillary acidic protein were present. Their distribution corresponded well to the spread of oedema, i.e. they were prominent around the leaky vessels in the grey matter, in the subpial zone and in the white matter. In the reparative phase the grey matter cysts became lined by astrocytic processes, a new glia limitans. Profuse sheets of glial processes in the neuropil around the cysts reestablished the compactness of the brain parenchyma.

Animals↗

PubMed1988

Observations on exsudation of fibronectin, fibrinogen and albumin in the brain after carotid infusion of hyperosmolar solutions. An immunohistochemical study in the rat indicating longlasting changes in the brain microenvironment and multifocal nerve cell injuries.

An immunohistochemical study was carried out on rat brain to determine if a transient opening of the blood-brain barrier (BBB), leading to extravasation of serum albumin, is also associated with exudation and cellular uptake of fibronectin and fibrinogen. Both of them might exert important biological effects provided that they pass the BBB and come into contact with cells of the brain parenchyma. Hyperosmolar solutions of urea or mannitol were infused in the carotid artery for 30 s to open the BBB and the animals were killed at various time intervals thereafter. Formaldehyde-fixed, paraffin-embedded material was used for immunohistochemical demonstration of extravasated proteins by an avidin-biotin peroxidase technique. Multifocal, often confluent areas of widely different sizes with signs of albumin extravasation were observed both in the grey and the white matter of the cerebral hemispheres exposed to the hyperosmolar solutions. Much less pronounced changes were observed in rats given an intracarotid saline infusion alone. Immunoreactive material indicating extravasation of fibronectin and fibrinogen was present in the infused cerebral hemispheres but albumin immunoreactivity was much more widespread. Reaction product was observed in vascular walls, presumably in extracellular spaces and in nerve cells. Immunoreactivity in the perikaryon of neurons formed different patterns in various cells. A granular type most probably represents accumulation of the proteins in lysosomal organelles after pinocytotic uptake into the neuron. The second so-called diffuse variety is presumably the result of a severe nerve cell injury with an uncontrolled leakage of proteins into the cytoplasm. Our results indicate that vascular walls, extracellular spaces, glial cells and neurons will be exposed to extravasated fibronectin and fibrinogen as well as to albumin and that antigenic sites in such compounds remain for a long period after the BBB opening. In addition, there are indications that carotid infusions of hyperosmolar solutions may cause nerve cell injuries in regions with BBB opening. These findings have obvious clinical and experimental significance.

Animals↗

PubMed1988

Nerve cell injury in the brain of stroke-prone spontaneously hypertensive rats.

The brain lesions in stroke-prone spontaneously hypertensive rats (SHRSP) are characterized by multifocal microvascular and spongy-cystic parenchymal alterations particularly in the gray matter. An essential feature of the lesions is the presence of edema with massive extravasation of plasma constituents as evidenced by specific gravity measurements, Evans blue technique and immunohistochemistry. The nerve cell injury occurring in the brain lesions in SHRSP is further characterized by light and electron microscopy in the present study. Two types of neuronal changes were seen within the blood-brain barrier (BBB) leakage sites. A small number of neurons with dark condensed nucleus and cytoplasm were found most often at the periphery of recent lesions. The majority of injured neurons were pale and showed intracellular edema confined to the dendrites and perikarya sparing axons and synapses. Their nuclei were well preserved with finely dispersed chromatin. The swollen and watery cell processes of neurons and astrocytes gave a spongy appearance to the neuropil. The intracellular edema seemed to result in cytolysis. The results suggest that primary anoxia-ischemia is not the major pathogenetic mechanism behind the nerve cell injury in severely hypertensive SHRSP, rather it is the massive BBB leakage and consequent brain edema that causes cytolytic destruction of neurons. Secondary focal ischemia as a consequence of occlusion in microvessels may, however, contribute to the nerve cell destruction.

Animals↗

PubMed1988

Structural changes in the rat brain after carotid infusions of hyperosmolar solutions. An electron microscopic study.

Infusion of hypertonic solutions into the carotid artery is one method by which the blood-brain barrier (BBB) can be opened transiently in experimental animals. This technique has also been tried in clinical situations in which an enhanced uptake of intravenously injected chemotherapeutic drugs into the brain is desired. We have previously found that infusion of hypertonic mannitol or urea into the carotid artery of the rat, leading to a BBB opening, is associated with light microscopic signs of cellular damage in the brain parenchyma. An electron microscopic study has now been made to obtain more detailed information about the events taking place in the rat brain 1 to 72 h after an intracarotid infusion of hyperosmolar solution of mannitol. Toluidine blue-stained semithin epon sections were also available for high-resolution light microscopy of brain samples from urea-infused animals. Intravenously injected Evan's blue dye was used to confirm that BBB opening had occurred as a consequence of the carotid infusions. The infused hemispheres had numerous structural changes. The dominating light microscopic alteration was the presence of multifocal lesions in the gray or the white matter with closely packed microvacuoles causing status spongiosus. Ultrastructurally the microvacuoles corresponded to very pronounced watery swelling of astrocytic processes and to a minor degree to expansion of dendrites and axons. There was also a light or moderate perivascular astrocytic swelling. In the "spongy" lesions as well as occasionally in non-vacuolated parts of the cerebral cortex, there were collapsed electron-dense neurons with pronounced mitochondrial alterations such as severe swelling associated with rupture of christae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Cerebral microangiopathy in stroke-prone spontaneously hypertensive rats. An immunohistochemical and ultrastructural study.

The morphology of cerebral microvessels was studied immunohistochemically and ultrastructurally in 6- to 9-month-old normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP) with a systolic blood pressure of 138 +/- 15 mm Hg, 189 +/- 9 mm Hg, and 258 +/- 30 mm Hg respectively. Regions with major opening of the blood-brain barrier (BBB) were revealed by an i.v. injection of Evans Blue. Multifocal BBB opening with massive leakage of plasma constituents rich in fibrinogen-fibrin-related antigen occurred in SHRSP with a blood pressure above 210-220 mm Hg. BBB-leakage sites were found in the cerebral cortex and the basal ganglia, most frequently in the arterial border zones. The perivascular tissue spaces were dilated within the BBB-leakage sites, in particular around arterioles. Damaged endothelial and smooth muscle cells were replaced by fibrin-like material, multiple layers of basement membranes and bundles of collagen fibrils surrounded by proliferated fibroblasts. The degenerative-infiltrative-proliferative disease process transformed short segments of single arterioles into severely thickened, tortuous and stenotic vessels. Fibrinoid degeneration, formation of microaneurysms and fibrin-rich vascular occlusions were observed. In contrast, only minor or no vascular alterations were seen in regions with preserved BBB in SHRSP and SHR. A severely increased intraluminal pressure load appears to be of major pathogenetic importance for breakdown of the BBB and initiation of the vascular disease process in SHRSP. However, since only short segments of a limited number of widely separated vessels are severely affected, and the number of affected vessels increase towards arterial end and border zones, additional predisposing and aggravating factors may play significant roles in the development of fibrinoid vascular lesions in arterial hypertension.

Animals↗

PubMed1988

Pathogenesis of substantia nigra lesions following hyperglycemic ischemia: changes in energy metabolites, cerebral blood flow, and morphology of pars reticulata in a rat model of ischemia.

A spectacular spongiotic lesion, symmetrical in distribution and restricted to the pars reticulata of the substantia nigra (SNPR) has recently been described in hyperglycemic rats surviving 1-18 h after a brief period of transient ischemia. The purpose of this study was to clarify the pathogenesis of the lesion. In order to study whether the lesion was due to changes occurring during ischemia, local cerebral blood flow (l-CBF) and energy metabolites were measured in the substantia nigra (SN) and in other brain areas. Furthermore, brains were examined by light and electron microscopy immediately after ischemia and in the early recirculation period. Autoradiographic CBF measurements showed ischemia flow levels in the SN of 30-40% of control, similar in normo- and hyperglycemic rats. Thus, although ischemic, this structure had a considerable amount of residual flow. There was also a corresponding partial preservation of the adenylate energy charge. However, lactate levels were high, and in hyperglycemic subjects they rose to values previously described during status epilepticus (about 25 mumol/g). In hyperglycemic animals, neuronal alterations were consistently present in SNPR by the end of the 10-min period of ischemia. They included clumping of nuclear chromatin and subplasmalemmal clearing of the perikaryon. Some mitochondrial swelling was present in neuronal perikarya and in dendrites. The normal alignment of microtubules in the dendrites was disturbed, but there was no or only slight swelling of the dendrites. Aggregation of synaptic vesicles was a conspicuous finding in axonal terminals, which were also slightly swollen. Otherwise, the axons appeared largely spared. Microvessels looked quite intact. Similar cellular changes were observed in the early recovery period. Dendrites, however, started to swell, and their expansion finally caused the spongiotic appearance of the pars reticulata. The appearance of the dendritic lesions is strongly suggestive of transmitter-mediated ("excitotoxic") damage. However, it seems likely that the marked acidosis is injurious as well. We tentatively conclude that both mechanisms interact to give the final lesion. The results, and those previously obtained in epileptic seizures, suggest that mitochondria of SN neurons and neuronal processes are particularly prone to damage.

Animals↗

PubMed1988

Adrenaline-induced hypertension: morphological consequences of the blood-brain barrier disturbance.

Acute hypertension may transiently open the blood-brain barrier (BBB). To determine whether such temporary exposure of the brain parenchyma to plasma constituents may lead to permanent morphological alterations, acute hypertension was induced by i.v. adrenaline in conscious rates given Evan's blue and horseradish peroxidase as tracers. The brain were perfused in situ 24 h later: 17 of 21 brains showed multifocal sites of extravasation of the tracers and of endogenous plasma albumin, fibrinogen and fibronectin identified by immunohistochemistry. The proteins spread locally in the parenchyma and were taken up by neurons. Within the leaking sites in the cortex, hippocampus, thalamus and basal ganglia some shrunken and grossly distorted acidophilic neurons were present. Focal areas of sponginess were observed in the subpial and subependymal zones. Thus, a transient opening of the BBB may lead to neuronal damage.

Animals↗

PubMed1988

Neuron-specific enolase is a marker of cerebral ischemia and infarct size in rat cerebrospinal fluid.

Neuron-specific enolase concentrations were measured in samples of rat cerebrospinal fluid obtained repeatedly before and after occlusion of the middle cerebral artery. A method for reliable, repeated sampling of cisternal cerebrospinal fluid was developed for this purpose. Occlusion of the middle cerebral artery induced cerebral infarcts of slightly variable size with good correlation to raised neuron-specific enolase concentrations. Sham operation caused only superficial cortical damage at the site of surgery and was followed by an early, slight, and transient increase in neuron-specific enolase concentration. With our technique, the development of cerebral infarcts can be studied in individual rats under experimentally controlled conditions over an extended period of time. Analysis of neuron-specific enolase can be used in trials of drugs for mitigating the effect of ischemia. Information concerning the release of neuron-specific enolase from ischemic cerebral tissue to the cerebrospinal fluid is important because neuron-specific enolase in the cerebrospinal fluid can be determined in patients suffering from cerebrovascular insult.

Animals↗

PubMed1987

Substantia nigra damage induced by ischemia in hyperglycemic rats. A light and electron microscopic study.

Preischemic hyperglycemia induced by feeding or glucose infusion worsens the brain damage and the clinical outcome following ischemia of a given duration and density, and characteristically causes postischemic seizure activity. Light microscopy has previously showed that, in the rat, transient hyperglycemia ischemia induced by bilateral carotid occlusion in combination with arterial hypotension causes a uni- or bilateral lesion in the pars reticulata of the substantia nigra. Since this region has a central role in preventing seizure discharges the present study was carried out to determine the ultrastructural characteristics of this lesion. In rats with 10 min of transient hyperglycemic ischemia followed by recirculation for 1 to 18 h, the pars reticulata of the substantia nigra showed signs of status spongiosus, as well as extensive nerve cell alterations. These changes were observed after all recovery periods studied. The spongiotic appearance was mainly caused by swelling of dendrites and, to a lesser degree, by astrocytic swelling. The dendrites were expanded at all recovery times but the severity increased during the later periods of recirculation. These swollen dendrites contained severely expanded mitochondrias and endoplasmic reticulum. The cytoskeletal elements showed disordered lining of microtubules. Two major types of nerve cell alterations were present: a "pale" and a "dark" variety. The pale type was the most frequent cell alteration. It occurred in all experimental groups and at all time points. Redistribution of the nuclear chromatin and of cytoplasmic organelles as well as swelling of the same type as in the dendrites were the essential changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Degeneration of trigeminal ganglion neurons caused by retrograde axonal transport of doxorubicin.

Selective nerve cell degeneration was induced in the trigeminal ganglion of the mouse by injecting doxorubicin (Adriamycin) around intact sensory nerve terminals of the head. The drug apparently reached the neurons by retrograde axonal transport after its uptake in nerve branches. A direct fluorescence microscopic method revealed that the compound accumulated in the neurons. Electronmicroscopy showed degeneration of these cells, beginning in the nucleolus and the nucleus. Doxorubicin injected around sensory nerve terminals appears to be a useful compound for selective destruction of mouse sensory neurons. Retrograde axonal transport of neurotoxic compounds is probably an important pathogenetic mechanism in certain forms of intoxication which give rise to lesions in the nervous system.

Animals↗

PubMed1986

Intravenous injection of horseradish peroxidase in the rat stimulates corticosterone and adrenocorticotropic hormone release.

Wistar rats were given intravenous (i.v.) horseradish peroxidase (HRP) in saline in doses commonly used to study vascular permeability and the blood-brain barrier. Samples of blood were taken from conscious animals via indwelling catheters at intervals up to 6 h after the HRP injection. Plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone were determined and compared with levels in control rats injected with saline alone. Rats injected with saline only presented levels of hormones within the low limits of normal indicating an insignificant influence of stress induced by the experimental procedure. Within 30 min of the i.v. HRP injection, the plasma concentrations of both ACTH and corticosterone increased to very high levels and remained so throughout the period of observation, namely 6 h. The time course of the changes in the concentrations was the same for the two hormones and the actual numerical values were related to the dose of HRP injected. The i.v. injection of HRP in Wistar rats, therefore, induces a marked release of stress hormones which by themselves have profound physiological effects. This phenomenon must be taken into account, in studies on normal vascular permeability using HRP as a tracer and also in similar experiments exploring various pathological conditions of the blood-brain barrier.

Adrenal Cortex↗

PubMed1986

Early axonal lesion and preserved microvasculature in epilepsy-induced hypermetabolic necrosis of the substantia nigra.

The time course of structural change in epilepsy-induced necrosis of the substantia nigra was studied by light and electron microscopy, and was correlated with previous metabolic studies. By light microscopy, tinctorial pallor appeared early, followed by pan-necrosis and macrophage infiltration. Mild lesions showed neuropil vacuolation but sparing of neurons, rather than a selective neuronal vulnerability. Electron microscopy of the evolving necrosis revealed an orderly sequence of structural damage involving first axons, then dendrites, neurons, and glia. No necrotic endothelial cells could be found, even in areas of apparent pan-necrosis by light microscopy. Pericytes near the vascular lumen were spared, whereas those in outer locations were necrotic. Edema, measured densitometrically, was absent. Previous metabolic studies of this lesion have demonstrated a pronounced focal lactic acidosis due to anaerobic hypermetabolism. Although the lesions resemble infarcts, hypermia rather than ischemia has been shown to accompany their development. Structural preservation of endothelial cells and inner pericytes likely stems from proximity to the moving blood stream, away from the site of lactic acid production in the neuropil. The findings indicate that the perfusion of necrotic tissue occurs via a persisting, intact microcirculation. The relative neuronal sparing and the early axonal rather than dendritic lesion show a clear distinction from excitotoxic pathology.

Animals↗

PubMed1986

Evaluation of the toxicity of subarachnoid clonidine, guanfacine, and a substance P-antagonist on rat spinal cord and nerve roots: light and electron microscopic observations after chronic intrathecal administration.

Clonidine has been reported to produce analgesia in man after epidural and intrathecal administration. In the present investigation the alpha 2-adrenoceptor agonists clonidine and guanfacine were tested to evaluate their potential spinal neurotoxic effects. Rats were injected daily for 14 consecutive days via catheters implanted in the intrathecal space. Clonidine was administered at a dose of 1.63 micrograms or 16.3 micrograms, and guanfacine at 16.3 or 75 micrograms. After perfusion with a buffered 3% glutaraldehyde solution, the spinal cords and nerve roots were taken for neuropathological analysis using light and electron microscopy. Compared to animals injected with 0.9% saline, clonidine and guanfacine gave rise to no detectable neurotoxic changes in the doses employed. An additional group of rats had intrathecal injections of a substance P-antagonist (D-Arg1, D-Trp7,9, Leu11)-substance P (spantide) with known neurotoxic effect as a test of the histotechnical methods used. Degenerative lesions, with a preference for the ventral horns, were consistently present in the grey matter of the cord in these animals. We conclude that the absence of detectable changes in rats given clonidine and guanfacine is probably a real expression of the low degree of toxicity for these compounds on rat spinal cord and nerve roots and not an artifact of the sensitivity of the histotechniques applied. The doses of clonidine administered were considerably greater than those reported to produce clinical greater than those reported to produce clinical analgesia.

Adrenergic alpha-Agonists↗

PubMed1986

The spread of brain oedema in hypertensive brain injury.

Severe hypertension in humans may lead to fibrinoid necroses of cerebral blood vessels with small hemorrhages and cystic necroses. Similar lesions have also been reported in the experimental model of stroke-prone spontaneously hypertensive rats (SHRSP). We examined the genesis and spreading pattern of the brain oedema in SHRSP. The extravasation of plasma proteins was visualized with the Evans-Blue or the immunoperoxidase method. Most commonly the leakage occurred in the grey matter of the cerebral cortex or basal ganglia. The spreading pattern followed that of vasogenic brain oedema with a local spread in the grey matter and an extensive one in the white matter. In addition, we detected a novel pathway upwards along the perivascular spaces of the penetrating vessels as well as laterally in the subpial zone. This route is likely to serve also as a drainage channel for the oedema into the cerebrospinal fluid in the subarachnoidal space. Transfer of the extravasated proteins from the white matter to the ventricles was also observed, confirming that this previously described pathway for the resolution of oedema fluid exists in the SHRSP model of vasogenic brain oedema.

Animals↗

PubMed1985

The dentate gyrus in hypoglycemia: pathology implicating excitotoxin-mediated neuronal necrosis.

A detailed light- and electron-microscopic study of the damage to the rat dentate gyrus in hypoglycemia was undertaken, in view of the previously advanced hypothesis that hypoglycemic nerve cell injury is mediated by a released neurotoxin. The distribution of neuronal necrosis showed a relationship to the subarachnoid cisterns. Electron microscopy of the dentate granule cells and their apical dendrites revealed dendrosomal, axon-sparing neuronal pathology. Dentate granule cells were affected first in the dendrites in the outer layer of the stratum moleculare, sparing axons of passage and terminal boutons. Subsequently, the neuronal perikarya were affected, and Wallerian degeneration of axons followed. Cell membrane abnormalities preceded the appearance of mitochondrial flocculent densities and degradation of the cytoskeleton, and are suggested to be early lethal changes. The observed early dendrotoxic changes, and the dendrosomal, axon-sparing nature of the lesion implicate an excitotoxin-mediated neuronal necrosis in hypoglycemia.

Animals↗