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J Krieglstein

Publications and source records attributed to J Krieglstein.

At least 109 records · Page 6Linked to original sources
PubMed1992

Calbindin-D28K and ischemic damage of pyramidal cells in rat hippocampus.

An antibody against rat calbindin-D28K, a calcium-binding protein present at high concentration in certain neurons of the central and peripheral nervous systems, was used to determine the progression of the pathological events in the rat hippocampus following experimental cerebral ischemia. Calbindin-D28K immunoreactivity is present in dentate granule cells and in the CA1-CA2 pyramidal cells. CA1 subfield contains a higher proportion of calbindin-D28K-positive pyramidal cells than does the CA2 subfield and CA1 cells are more immunoreactive than the CA2 cells. The pyramidal cells of the CA1 and CA2 subfields are vulnerable to ischemia. The cells in the CA1 became necrotic within 3-4 days after ischemia while those of the CA2 became necrotic within 2 days. There was a concomitant decrease in calbindin-D28K immunoreactivity in the whole hippocampal regio superior after ischemia which peaked 3 days postischemia. The difference in CA2 and CA1 vulnerability seemed to be inversely correlated with the calbindin-D28K contents of the CA2 and CA1 pyramidal cells. The decrease in the calbindin-D28K contents of these neurons was accompanied by cell damage. We therefore suggest that calbindin-D28K is an important factor for the survival of pyramidal cells in the hippocampal formation after ischemia.

Animals↗
PubMed1992

Thyroxine attenuates hippocampal neuronal damage caused by ischemia in the rat.

We investigated the effect of thyroxine against neuronal damage caused by ischemia in the rat. Neuronal damage was evaluated in the hippocampal CA1 subfield 7 days after a 10 min forebrain ischemia. Thyroxine was administered to animals divided in three groups: 15 min prior to ischemia (group 1), immediately after ischemia (group 2), and both before and after ischemia (group 3). The treatment of rats with a single dose of thyroxine given pre- or postischemia failed to prevent the loss of CA1 pyramidal cells. In contrast, repetitive administration of thyroxine before and after ischemia reduced the damage of the CA1 pyramidal cells. The mechanisms possibly underlying this neuroprotective effect are discussed.

Animals↗
PubMed1992

Effects of stimulation of putative dopamine autoreceptors on electroencephalographic power spectrum in comparison with effects produced by blockade of postsynaptic dopamine receptors in rats.

Alterations in cortical EEG activity in male rats produced by putative agonists at dopamine (DA) autoreceptors and by antagonists at postsynaptic DA receptors were compared in order to study, whether an impairment in dopaminergic neurotransmission via two different mechanisms might result in similar or different effects. Simultaneously to the EEG recordings, gross behaviour was observed. Putative agonists at DA autoreceptors (apomorphine 0.05 mg/kg, quinpirole 0.05 mg/kg, or talipexole 0.02 mg/kg s.c.) produced increases in the power in all of the frequency bands, except beta-2, with the most pronounced increase in the delta band. These EEG alterations were accompanied by hypokinesia, ptosis and yawning. In contrast, antagonists at DA receptors (haloperidol 0.1 mg/kg i.p., D2 blocker) or SCH 23390 (0.2 mg/kg i.p., D1 blocker) led to little increases in the delta band, but more pronounced increases in the alpha-2 band. Behavioural signs were hypokinesia, but little ptosis and yawning. The combination of both blockers produced, in addition, strong increases in the delta band and behavioural signs of ptosis and yawning. These results suggest that activation of putative dopamine autoreceptors produces EEG patterns and behavioural patterns different from those produced by blockade of either D1 or D2 postsynaptic dopamine receptors. In contrast, the effects following a stimulation of putative DA autoreceptors, which are expected to decrease the release of the agonist and its action at postsynaptic D1 and D2 receptors, were very similar to those found after a combined blockade of both types of postsynaptic dopamine receptors.

Animals↗
PubMed1992

Prevention of ischemia-induced cerebral hypothermia by controlling the environmental temperature.

Regulation of brain temperature during and after cerebral ischemia plays an important role in the evolution of neuronal damage. Therefore, it is essential to maintain brain temperature at 37 degrees C during and after the ischemic insult. To get information about brain temperature during the experimental procedure, researchers in previous works have made various attempts to correlate between brain and body temperature during and after ischemia. In the present study, brain temperature was measured when ischemia was performed either at 30 degrees C or at 20 degrees C environmental temperature. For this purpose a stainless-steel guide of a temperature probe was introduced through the bregma and implanted between both hemispheres of the rat. Rats were then subjected to a 10-min period of forebrain ischemia. Cerebral temperature was measured during ischemia and up to 90 min; in some experiments up to 4 hr after ischemia. In another group of experiments, ischemia was performed also at either 30 degrees C or 20 degrees C environmental temperature, and histological assessment of the rat hippocampus was carried out. In addition, the influence of chlorpromazine as a hypothermic agent on the cerebral temperature and the neuronal loss was also tested at both of the experimental conditions. Recording the brain temperature at both of the selected environmental temperatures suggests that it is possible to preserve cerebral normothermia during and after ischemia by working at 30 degrees C environmental temperature. On the other hand, brain temperature dropped sharply immediately after ischemia when working under 20 degrees C environmental temperature, and brain tissue was thereby protected against ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A mouse model of focal cerebral ischemia for screening neuroprotective drug effects.

The aim of the present study was to investigate if the infarct area on the brain surface after middle cerebral artery (MCA) occlusion in the mouse is representative for the infarct volume and if this determination of brain injury can be used for screening neuroprotective drug effects. Cerebral infarction was induced by coagulating electrically the stem of the left MCA. After 48 hr, the brains were perfused with carbon black and the unstained infarct area was determined by means of an image analyzing system. The infarct volume was determined by calculating the infarct area on coronal slices and the distance between succeeding slices. The correlation between the area and the volume of infarction was significant (r = 0.81; p less than 0.001). N-methyl-D-aspartate (NMDA) antagonists, calcium antagonists, 5-hydroxytryptamine-1A (5-HT-1A) agonists, radical scavengers, and various drugs were investigated in the mouse model of MCA occlusion. Drugs were usually applicated before ischemia. The drugs that were found to be neuroprotective in the mouse model revealed similar effects in rat models of focal or global cerebral ischemia. These findings show that the presented mouse model with its simple technique of measuring the infarct size is suitable for screening purposes.

Animals↗
PubMed1992

Dihydrolipoate reduces neuronal injury after cerebral ischemia.

It has been shown in vitro that dihydrolipoate (DL-6,8-dithioloctanoic acid) has antioxidant activity against microsomal lipid peroxidation. We tested dihydrolipoate for its neuroprotective activity using models of hypoxic and excitotoxic neuronal damage in vitro and rodent models of cerebral ischemia in vivo. In vitro, neuronal damage was induced in primary neuronal cultures derived form 7-day-old chick embryo telencephalon by adding either 1 mM cyanide or 1 mM glutamate to the cultures. Cyanide-exposed and dihydrolipoate-treated (10(-9)-10(-7) M) cultures showed an increased protein and ATP content compared with controls. The glutamate-exposed cultures treated with dihydrolipoate (10(-7)-10(-5) M) showed a decreased number of damaged neurons. In vivo, dihydrolipoate treatment (50 and 100 mg/kg) reduced brain infarction after permanent middle cerebral artery occlusion in mice and rats. Dihydrolipoate treatment (50 and 100 mg/kg) could not ameliorate neuronal damage in the rat hippocampus or cortex caused by 10 min of forebrain ischemia. A comparable neuroprotection was obtained by using dimethylthiourea, both in vitro (10(-7) and 10(-6) M) and at a dose of 750 mg/kg in the focal ischemia models. Lipoate, the oxidized form of dihydrolipoate, failed to reduce neuronal injury in any model tested. We conclude that dihydrolipoate, similarly to dimethylthiourea, is able to protect neurons against ischemic damage by diminishing the accumulation of reactive oxygen species within the cerebral tissue.

Animals↗
PubMed1992

Activated astrocytes, but not pyramidal cells, increase glucose utilization in rat hippocampal CA1 subfield after ischemia.

The local cerebral glucose utilization (CMRglc) in the damaged rat hippocampal CA1 subfield increases 7 days after 10 min of cerebral ischemia. We have used the N-methyl-D-aspartate antagonist (NMDA antagonist) ketamine in rats 7 days after sham operation or cerebral ischemia to determine whether the elevated postischemic CMRglc of the CA1 subfield is due to long-lasting hyperexcitation of surviving or injured neurons, or, alternatively, to the metabolism of other cell types. The autoradiographic data were interpreted with the aid of histochemical analysis of the postischemic hippocampal cell changes. Anesthetic doses of ketamine significantly reduced the CMRglc in the CA1 strata oriens, pyramidale and radiatum of sham-operated rats, while the postischemic increases in CMRglc in these hippocampal CA1 strata were not affected by ketamine. In addition, there were ketamine-induced increases in the CMRglc of the CA1 stratum lacunosum moleculare of both sham-operated and postischemic rats. The immunoreactivity of the microtubule-associated protein 2 (MAP2), a postsynaptic protein marker, was decreased markedly in the CA1 subfield in postischemic rats, while the presynaptic protein marker, synaptophysin, remained the same in sham-operated and postischemic rats. The glial fibrillary acidic protein (GFAP) immunoreactivity of astrocytes raised markedly in the ischemically damaged CA1 subfield. Although it could be demonstrated that presynaptic terminals remain intact in the postischemic damaged CA1 subfield, the lacking ketamine effect on CA1 pyramidal neurons indicated that the increase in CMRglc in this brain area is not due to postsynaptic neural hyperexcitation, but probably has to be attributed to astrocytes activated by neuronal damage.

Animals↗
PubMed1992

Cerebral energy metabolism in immature and mature guinea pig fetuses during acute asphyxia.

In immature fetuses circulatory centralization caused by acute asphyxia is less effective than that in mature fetuses (Jensen & Berger, 1991). This suggests that cerebral oxygenation may be poor in immature fetuses during asphyxia. On the other hand cerebral oxygen consumption is lower in immature than that in mature fetuses. To determine, whether or not there is an imbalance between oxygen supply and demand in one or the other group, we compared the time course of the changes of cerebral concentrations of both high-energy phosphates and glycolytic intermediates between immature and mature guinea pig fetuses during acute asphyxia caused by arrest of uterine blood flow. The fall in the cerebral concentrations of adenosine triphosphate and glucose, and the rise in those of adenosine monophosphate and lactate were slower in immature than in mature fetuses. There were no differences between the levels of cerebral adenosine diphosphate and creatine phosphate of the two groups. From these results we conclude that during acute asphyxia the imbalance between cerebral oxygen supply and demand is less marked in immature than in mature fetuses.

Acute Disease↗
PubMed1991

Vinpocetine increases the neuroprotective effect of adenosine in vitro.

Cultured neurons from chick embryo cerebral hemispheres were used to study the neuroprotective activity of vinpocetine and adenosine against hypoxic damage. Cytotoxic hypoxia was induced by adding 1 mM sodium cyanide to the nutrient medium for 30 min. The drugs were present in the nutrient medium 30 min before, and up to 1 day after hypoxia. To characterize the neuroprotective drug effects, the protein content per culture flask and the neuronal viability were determined 3 days after this hypoxic period. Adenosine, but not vinpocetine, was able to protect neurons against hypoxic damage, when added as single drug to the cultures. However, vinpocetine significantly enhanced the neuroprotective effect of adenosine. The results suggest that the neuroprotective effect of vinpocetine is mediated by adenosine.

Adenosine↗
PubMed1991

Neuroprotective properties of 5-HT1A receptor agonists in rodent models of focal and global cerebral ischemia.

5-Hydroxytryptamine1A (5-HT1A) receptor agonists have been shown to inhibit the activity of hippocampal, cortical, and dorsal raphé neurons. We tested urapidil and a new 5-HT1A agonist, CM 57493 [4-(3-trifluoromethylphenyl)-1-(2-cyanoethyl)-1,2,3,6-tetrahydropyridine ], for their neuroprotective activity in models of focal and global cerebral ischemia in rodents. After middle cerebral artery-occlusion (MCA-0) in mice, the infarct size was reduced dose dependently by both urapidil and CM 57493. In MCA-occluded rats, CM 57493 (1 and 5 mg/kg) reduced the cortical infarct volume by 30% and application of 10 mg/kg CM 57493 led to a 40% reduction in the cortical infarct volume. The striatal damage could not be influenced by CM 57493 treatment. Furthermore, 1 and 5 mg/kg CM 57493 significantly reduced the neuronal damage within the CA1 sector of the rat hippocampus after 10 min of forebrain ischemia followed by 7 days of recovery. Measurement of cerebral and rectal temperature revealed that the neuroprotective effect of CM 57493 was not caused by a hypothermic effect. We assume that the neuroprotective activity of 5-HT1A agonists is mediated by an inhibitory action on neurons.

Animals↗
PubMed1991

Conditioning of apomorphine effects: simultaneous analysis of the alterations in cortical electroencephalogram and behaviour.

The possible conditioning of pharmacological effects of apomorphine on the electroencephalogram was studied using telemetric recordings in rats. Previous studies have shown that apomorphine-induced stereotyped behaviour can be conditioned: after repeated pairings of defined stimuli with the drug effect, the presentation of the external stimuli alone elicited stereotype sniffing, licking, and gnawing. Since apomorphine, an agonist at dopamine receptors, also produces a characteristic EEG pattern with an increase of power in the alpha-1 band, the possibility that this effect could also be conditioned was studied. In fact, conditioning with a dose of 0.5 mg/kg apomorphine (s.c.) led to a significant increase in the number of short-lasting episodes with enhancement of the power in the alpha-1 range in the presence of the conditioned stimuli, according to a comparison of the results obtained in the conditioned group and those of the controls ("pseudoconditioned"). Moreover, behavioural studies were performed simultaneously in order to find possible correlations between conditioned effects on EEG and conditioned alterations in behaviour. In general, a fair correlation between the increase of power in the alpha-1 band and stereotyped behaviour was found. This was also the case during extinction, when the conditioned stimuli were repeatedly uncoupled from apomorphine administration: both behavioural parameters and EEG alterations showed similar time-courses and had almost disappeared during the fourth extinction session.

Animals↗
PubMed1991

Neuroblastoma cells for testing neuroprotective drug effects.

An attempt was made to use neuroblastoma cells for testing neuroprotective drug effects. To achieve cellular damage, cytotoxic hypoxia was induced in neuroblastoma cells after 10 days in culture by addition of sodium cyanide (1 mmol/L) to the culture medium and was terminated after 6 hr by replacing the cyanide-containing fresh nutrient medium. During this hypoxic period cells were additionally deprived of glucose. They were allowed to recover for another 7 days. Drugs were available to the cells from 30 min prior to hypoxia until 24 hr after hypoxia. Cell concentration of high-energy phosphates and culture protein content were determined as representatives for the posthypoxic development of cell damage, cell activity and viability. While barbiturates and phenytoin revealed neurotoxic effects when applied in doses higher than 300 mumol/L, chlorpromazine, dizocilpine, ketamine, ketazocine, naftidrofuryl, and flunarizine protected neuroblastoma cells against hypoxic damage. These results were comparable to those obtained from primary cultures of neurons under similar experimental conditions. In addition, they were in keeping with neuroprotective drug effects obtained from in vivo experiments. It is suggested that neuroblastoma cells are suitable for testing neuroprotective drug effects.

Cell Hypoxia↗
PubMed1991

Postischemic neuronal damage causes astroglial activation and increase in local cerebral glucose utilization of rat hippocampus.

The purpose of the present study was to determine the consequences of postischemic neuronal damage on CMRglc. Forebrain ischemia of 10 min duration was induced in male Wistar rats. The extent of neuronal damage and the numbers of immunocytochemically detected astrocytes in the hippocampal CA1 subfield as well as CMRglc were determined 2, 5, 7, and 14 days after ischemia. CBF was additionally measured 7 days postischemia. CMRglc was decreased in cortical and thalamic structures up to 5 days postischemia, and was normalized again on day 7 after ischemia. In the hippocampal areas, CMRglc was decreased only on day 2 after ischemia, was normalized after 5 days, and increased in the stratum oriens and pyramidale of the CA1 subfield from postischemic day 7 onward. Neuronal damage was clearly demonstrable 5 days after ischemia and further increased up to day 7. The number of GFAP-reactive astrocytes increased markedly at day 7 postischemia. It is assumed that the activation of astrocytes is induced by neuronal damage, and that the astroglial metabolism is responsible for the increase in CMRglc of the CA1 subfield 7 days after ischemia. The decrease in CBF of the CA1 subfield 7 days after ischemia could be caused by a reduced density of perfused capillaries.

Animals↗
PubMed1991

Preischemic administration of flunarizine or phencyclidine reduces local cerebral glucose utilization in rat hippocampus seven days after ischemia.

The purpose of the present study was to investigate the influence of ischemia on postischemic metabolic activity of the brain. Furthermore, the effect of preischemic application of neuroprotective agents such as flunarizine or phencyclidine on postischemic local cerebral glucose utilization (LCGU) was examined. Forebrain ischemia in the rat was performed for 10 min with bilateral carotid clamping, administration of trimethaphan and blood withdrawal to obtain a mean arterial blood pressure of 40 mm Hg. LCGU was determined 7 days after ischemia by injecting 14C-deoxy-D-glucose in saline solution. A significant increase in LCGU in the CA1 subfield of the hippocampus was found 7 days after ischemia, whereas preischemic administration of flunarizine or phencyclidine inhibited this increase. Alterations in LCGU of other brain regions were insignificant.

Animals↗
PubMed1991

Protective effect of vinpocetine against brain damage caused by ischemia.

The effects of vinpocetine against hippocampal neuronal damage and on local cerebral blood flow (LCBF) were examined in a rat model of forebrain ischemia (10-min occlusion of the carotid arteries and hypotension). Histological evaluation of neuronal loss in the hippocampus was performed 7 days after ischemia. LCBF was measured before ischemia as well as after 2 min and 1 hr of recirculation. Vinpocetine (10 mg/kg) administered pre- or post-ischemically reduced the hippocampal neuronal necrosis, while pre-ischemic administration of 2 or 20 mg/kg vinpocetine was ineffective. Since vinpocetine increased the LCBF after 1 hr of recirculation, it cannot be excluded that blood flow improvements contribute to its neuroprotective activity. On the other hand, there is no clear evidence that an elevation of post-ischemic hypoperfusion could protect neurons against ischemic damage. It is, therefore, suggested that vinpocetine acts directly on brain cells.

Animals↗
PubMed1991

Effects of acute asphyxia on brain energy metabolism in fetal guinea pigs near term.

In a previous study we suggested that--unlike other forms of asphyxia--acute asphyxia caused by arrest of uterine blood flow is accompanied by a fall in oxygen delivery to the fetal brain (Jensen et al., 1987). This may change cerebral energy metabolism by causing an increase in the glycolytic rate. To test this hypothesis we studied the time course of the changes in the levels of high-energy phosphates and glycolytic intermediates in the cerebral cortex of unanaesthetized fetal guinea pigs near term before and after 2 and 4 min of acute asphyxia. During asphyxia there was a progressive fall of adenosine triphosphate, creatine-phosphate, glucose and fructose-1,6-diphosphate concentrations, whereas adenosine diphosphate, adenosine monophosphate and lactate concentrations increased. Pyruvate concentrations did not change. We conclude that fetal cerebral energy metabolism becomes increasingly anaerobic during acute asphyxia caused by arrest of uterine blood flow, because oxygen delivery to the fetal brain falls.

Animals↗
PubMed1991

Cerebral energy metabolism in guinea pig fetuses during development.

During development fetal arterial oxygen tension falls, whereas cerebral oxygen consumption rises due to an increase in cerebral metabolism. To compensate for this increase in oxygen consumption, blood flow and therefore oxygen delivery to the cerebrum rises. To determine whether during development oxygen delivery to the cerebrum meets cerebral oxygen consumption, we measured the concentrations of high-energy phosphates and glycolytic intermediates in the cerebral cortex of fetal guinea pigs at different gestational ages. During development there was no change in the concentrations of adenosine triphosphate, creatine phosphate, adenosine monophosphate, and lactate. However, cerebral concentrations of adenosine diphosphate increased and those of glucose decreased. Our results suggest that the increase in fetal cerebral oxygen delivery during development meets cerebral oxygen consumption with increasing gestational age. We speculate that the measured rise in the concentrations of adenosine diphosphate may accelerate glycolysis during development and therefore may cause a rise in both cerebral blood flow to maintain oxygen delivery.

Adenosine Diphosphate↗