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H Kalimo

Publications and source records attributed to H Kalimo.

At least 181 records · Page 10Linked to original sources
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

Brain lactic acidosis and ischemic cell damage: quantitative ultrastructural changes in capillaries of rat cerebral cortex.

Excessive tissue lactic acidosis has earlier been shown to aggravate structural damage of both neurons and glial cells in the rat cerebral cortex. To study the reactions of cortical capillaries, light- and electronmicroscopic morphometry was used. Rats were subjected to severe incomplete ischemia (cerebral blood flow below 5% of normal) for 30 min by clamping their carotid arteries and by lowering the blood pressure. Lactate production during ischemia was modified by preischemic administration of either saline (low lactic acidosis group) or glucose (high lactic acidosis group). In the animals with low lactic acidosis, only minimal vascular changes were seen after both 5 min and 90 min recirculation. In the high lactic acidosis group, the endothelial cells were swollen after 5 min of recirculation, and the changes grew markedly worse during 90 min of recirculation. Nuclear chromatin coarsened and mitochondria swelled up. Morphometry showed that the lumen narrowed as a result of endothelial swelling. In spite of variable degree of perivascular astrocytic edema, the outer capillary diameter was little changed in the experimental groups. It seems likely that endothelial swelling hampers postischemic circulation in incomplete ischemia accompanied by high lactic acidosis.

Acidosis↗
PubMed1983

Cholinesterase activities in the somatic nervous system of rabbits with experimental allergic neuritis.

The allergic inflammatory disorders of the nervous tissue are associated with a complex series of cellular and humoral immune activities and they usually result at least in demyelination, but according to morphologic evidence also in secondary neuronal changes. Using the colorimetric method of Ellman et al. (G. L. Ellman, K. D. Courtney, V. Anders, and R. M. Featherstone, 1961, Biochem. Pharmacol. 7:88-95) the activities of enzymes splitting acetylthiocholine iodide (AThCh) were determined from various parts of the somatic nervous system of rabbits with experimental allergic neuritis (EAN), a primary demyelinating disease of the peripheral nerves. It was found that the total activity of AThCh-splitting enzymes was decreased already in an early phase of the disease in the dorsal root ganglia (DRG). In a well developed phase of the disease the activity of acetylcholinesterase (AChE) seemed to be decreased by 33% in the ventral roots and by a lesser amount in the DRG and the most proximal part of the sciatic nerves. The mechanism of the recorded changes may be related either to specific or to nonspecific immune events or to both. Proteolytic activity released by macrophages in the target tissue may, by inactivating the hydrolytic activity of AChE, at least partly explain these findings. Because the activity of AChE in the structures studied derives from a neuronal origin, our results provide biochemical evidence for the involvement of neurons in the sensory ganglia and of axolemma in the ventral roots in EAN.

Acetylthiocholine↗
PubMed1982

Involvement of autonomic nervous system in experimental allergic neuritis. A light- and electron-microscopic study.

The affection of the sympathetic and parasympathetic structures of the peripheral nervous system in rabbits with experimental allergic neuritis (EAN) was demonstrated light- and electron-microscopically. The general characteristics of the microscopic findings were qualitatively similar to those previously established in the somatic nervous system, but they were less extensive. The neuronal perikarya and the axons in the autonomic nervous system (ANS) were mostly normal. Occasionally, cytoplasmic vacuoles in a few nodose ganglion neurons and some degenerating axons were seen. Other than myelin derived antigens could be operating in whole-nerve induced EAN, since inflammatory cells also infiltrated target tissue areas devoid of myelinated nerve fibers. The presence of numerous plasma cells in the target tissue suggests that local antibody formation may contribute to the destructive process. Our results establish that the ANS is frequently affected in EAN, especially in the more severe forms. Thus EAN was proved to be also in this respect a useful model for the human disease Guillain-Barré syndrome, which likewise is often complicated by autonomic dysfunctions.

Animals↗
PubMed1981

The role of lactic acidosis in the ischemic nerve cell injury.

Severe incomplete cerebral ischemia of 30 min duration with CBF below 5% of normal was induced in rats by clamping both carotids and lowering BP. One group of rats were fasting (f-rats), while the other was infused with glucose before induction of the ischemia (g-rats). In f-rats the lactate accumulating in the cerebral cortex was about 15 mumol . g-1, whereas in g-rats it rose to about 35 mumol . g-1. In f-rats considerable recovery of the energy state and electrical activity occurred during recirculation, whereas in g-rats the energy failure persisted with no electrical activity reappearing. In f-rats the structural alterations were of minor severity, but in g-rats extensive progressive tissue damage was seen. The data indicate that the degree of tissue lactic acidosis has pronounced effects on the development of irreversible ischemic nerve cells injury.

Animals↗
PubMed1981

Pathogenesis of brain lesions caused by experimental epilepsy. Light- and electron-microscopic changes in the rat cerebral cortex following bicuculline-induced status epilepticus.

Status epilepticus was induced in rats by the GABA receptor blocking agent, bicuculline, during artificial ventilation and with closely monitored physiologic parameters. After 1 or 2 h of status epilepticus the brains were fixed by perfusion with glutaraldehyde and processed for light and electron microscopy. In the cerebral cortex two different types of changes were present, i.e., nerve cell injuries and status spongiosus. Type 1 injured neurons, mainly in the areas of most marked sponginess (layer 3), displayed progressive condensation of both karyo-and cytoplasm. In the most advanced stages the nucleus could no longer be distinguished from the cytoplasm in the light microscope, and vacuoles of apparent Golgi cisterna origin appeared in the darkly stained cytoplasm. This type of injured neurons comprised 41 and 56% of the cortical neurons after 1 or 2 h of status epilepticus, respectively. Seven to 9% of the neurons showed another type of injury (type 2). They were mainly located in the deeper cortical layers, and showed slit-formed cytoplasmic vacuoles chiefly due to swelling of the endoplasmic reticulum including the nuclear envelope. Marked sponginess of the cortex developed principally in layer 3 and it spread into deeper layers with longer duration of status epilepticus, but the outermost layers retained a compact structure. As judged by electron microscopy, the sponginess resulted mainly from swelling of astrocytes and their processes causing both perivascular and perineuronal vacuolation. The structural changes observed are considered to be caused by astrocytic and to a lesser extent intraneuronal edema related to the seizure activity. Although the exact pathogenetic mechanisms are not known, our findings indicate that hypoxia-ischemia is not a major determinant of the tissue damage observed.

Animals↗