Torsten Olsson

IGF-I has a direct proliferative effect in adult hippocampal progenitor cells

The aim of the present study was to investigate the potential direct effects of insulin-like growth factor-I (IGF-I) on adult rat hippocampal stem/progenitor cells (AHPs). IGF-I-treated cultures showed a dose-dependent increase in thymidine incorporation, total number of cells, and number of cells entering the mitosis phase. Pretreatment with fibroblast growth factor-2 (FGF-2) increased the IGF-I receptor (IGF-IR) expression, and both FGF-2 and IGF-I were required for maximal proliferation. Time-lapse recordings showed that IGF-I at 100 ng/ml decreased differentiation and increased proliferation of single AHPs. Specific inhibition of mitogen-activated protein kinase kinase (MAPKK), phosphatidylinositol 3-kinase (PI3-K), or the downstream effector of the PI3-K pathway, serine/threonine p70 S6 kinase (p70(S6K)), showed that both the MAPK and the PI3-K pathways participate in IGF-I-induced proliferation but that the MAPK activation is obligatory. These results were confirmed with dominant-negative constructs for these pathways. Stimulation of differentiation was found at a low dose (1 ng/ml) of IGF-I, clonal analysis indicating an instructive component of IGF-I signaling.

Development of visual and somatosensory evoked responses in pre-term newborn infants

Abstract In 48 newborns born at 24–42 weeks gestational age computer-averaged visual (VERs) and somatosensory (SERs) evoked responses were studied. The following results were obtained: 1. 1. In pre-term newborn infants below 30 weeks gestation the main or only component was a very slow negative wave, most distinct in the corresponding projection area. In the two modalities studied the response patterns were similar but not identical. 2. 2. During further development the slow negative wave gradually decreased and faster components appeared. VER and SER became more and more dissimilar. 3. 3. Constant primary components appeared after 29 weeks gestation in SER and between 32 and 35 weeks in VER. 4. 4. Non-specific SERs at the vertex and in ipsilateral leads increased during development. 5. 5. The latencies of both responses decreased. age was linear after 30 weeks gestation. age was linear after 30 weeks gestation. 6. 6. The amplitude generally decreased during development. Evoked responses are a suitable tool for developmental studies in man because of the close dependence of their variables on cerebral maturation.

Clinical application of evoked electroencephalographic responses in newborn infants. I: Perinatal asphyxia.

Evoked electroencephalographic responses are useful for the study of cerebral maturation in full‐term and pre‐term newborn infants. In an attempt to achieve wider clinical application, 57 newborn infants with differing degrees of perinatal asphyxia were examined. Altogether 154 examinations were performed. In all of them photostimulation was used, and in 72 investigations somatosensory evoked responses were also recorded. The following results were obtained:

The Physiologic Effects of Surfactant Treatment on Gas Exchange in Newborn Premature Infants with Hyaline Membrane Disease

ABSTRACT: To describe the physiologic effects of surfactant treatment on gas exchange in human premature infants with hyaline membrane disease, functional residual capacity (FRC), tidal volume (VT), the alveolar portion of tidal volume (VA), alveolar ventilation (VA), nitrogen clearance index, effective breath fraction calculated as VA/VT, compliance of the respiratory system, and arterial oxygen and carbon dioxide tensions were measured in 17 patients before and 0.5, 2, and 6 h after the administration of a single dose of either a synthetic surfactant (SS), Exosurf (n = 10), or a bovine surfactant (BS), Survanta (n = 7). By 2 h, treatment with either BS or SS was followed by an increase in the arterial/alveolar ratio of Po2 (a/A) and in FRC (p < 0.01 for both a/A and FRC). The a/A and FRC improved sooner (p < 0.001) and to a greater extent (p < 0.01) after BS than after SS. Compliance of the respiratory system and VT were decreased after either BS or SS at 0.5 h (p < 0.01) and remained decreased after SS at 2 h (p < 0.01). There was no significant change in VA or VA after either BS or SS. Because FRC and a/A increased without an accompanying increase in VA, VA, or compliance of the respiratory system, we believe that the immediate increase in FRC in this study was caused by stabilization of gas exchange units already being ventilated in addition to recruitment of new units. Nitrogen clearance index decreased and effective breath fraction increased after treatment, indicating an improved efficiency in gas mixing also thought to result from stabilization and maintenance of patency of distal airways by surfactant.

Acute ethanol exposure induces [Ca2+]i transients, cell swelling and transformation of actin cytoskeleton in astroglial primary cultures.

Acute exposure to 100 mm isotonic ethanol (EtOH) increased intracellular Ca2+ concentration ([Ca2+]i), induced cell swelling, and transformed actin cytoskeleton in astroglial primary cultures from rat cerebral cortex. Fluorometric recordings of fluo‐3AM‐ or fura‐2AM‐incubated astroglial cells revealed that EtOH induced [Ca2+]i transients in a small population of the cells. Cell swelling was estimated using a new method based on three‐dimensional fluorescence imaging in conjunction with image analysis and graphic visualization techniques. The method provides detailed results concerning the reformation of structural shape and specific volume alterations, as well as total proportions between the different states. Astroglial cell swelling was registered and quantified in 7 of 39 cells chosen from 12 different coverslips. EtOH also induced reversible conformational changes in filamentous actin, appearing as increases in ring formations and a more dispersed appearance of the filaments. Filamentous actin was stained with Alexa phalloidin after incubation with EtOH for varied periods. The results presented here suggest that EtOH affects astrocytes in a way that could be of physiological relevance.

5-Hydroxytryptamine and glutamate modulate velocity and extent of intercellular calcium signalling in hippocampal astroglial cells in primary cultures

The effects of 5-hydroxytryptamine or glutamate treatment on mechanically induced intercellular calcium waves were studied in gap junction-coupled astroglial cells using rat astroglial-neuronal primary cultures from hippocampus. Imaging software was developed to study amplitude, velocity and extent of wave propagation. Velocity software was designed to find the cell contours automatically and to calculate travelled distance and time-delay of the calcium wave as it propagates from the stimulated cell to all other cells. Propagation analyses were performed to calculate the area of wave propagation. Mechanical stimulation of a single astroglial cell induced an intercellular calcium wave spreading from cell to cell in the astroglial syncytium. When registering the appearances of calcium signals in individual cells along the wave path upon re-stimulation of the same cell, 44.7% of the cells responded with similar calcium signal appearances the second time as the first time. A second wave from the opposite direction resulted in similar calcium signal appearances in 27.3% of the studied cells. Both amplitude and velocity of the calcium signal decreased most prominently in the first part and showed a later flattening out. Treatment with 5-hydroxytryptamine or glutamate for 20-30 s before mechanical stimulation increased the velocity of the calcium waves. 5-Hydroxytryptamine treatment for varying times decreased the propagation area of the calcium waves. In contrast, glutamate treatment increased the propagation area.

Cerebral Reactions during Intrauterine Asphyxia in the Sheep. I. Circulation and Oxygen Consumption in the Fetal Brain

Extract: Cerebral blood flow (CBF) with the 133Xe clearance technique and cerebral oxygen consumption were measured in the fetal lamb using chioralose-anesthetized ewes and acutely exteriorized fetuses with intact umbilical circulation. To induce fetal hypoxia at different pH levels, three different procedures were used: (1) the ewe was ventilated with a hypoxic gas mixture, containing 8–15% O2 in N2; (2) 5–10% CO2 was added to the hypoxia gas mixture; (3) during hypoxia a continuous rapid infusion of NaHCO3 solution was given intravenously to the fetus. Blood gas tensions, pH, and oxygen saturation were measured repeatedly.Multiple regression analysis was carried out on the data with the variables SaO2, PaO, PaO2, and pH considered as independent variables and flow as the dependent variable. All complete sets of observations were used amounting to 74 observations in 11 animals. No significant correlation was found between CBF and pH. SaO2 showed the highest correlation to CBF. No further improvement of this correlation was obtained when PaCO2 was added as independent variable. PaO2 and PaCO2 described jointly the variations of CBF as well as SaO2 alone.The oxygen consumption of the brain decreased during hypoxia when SaO2 was reduced below 40%. The decrease of the metabolic rate for oxygen was a function both of the degree of hypoxia and of pH. When an acidosis was added to the hypoxia a significant reduction of the oxygen consumption of the brain resulted compared with the same degree of hypoxia at normal or only moderately reduced pH levels.Speculation: The cerebral blood flow of the fetal lamb is regulated mainly via the amount of oxygen available to the brain, and changes of CO2 tension affect CBF via a displacement of the hemoglobin dissociation curve.Cerebral oxygen consumption is reduced to dangerously low levels when a severe acidosis is combined with hypoxia because of a failure to extract the oxygen available in the arterial blood.

Implications for glycine receptors and astrocytes in ethanol-induced elevation of dopamine levels in the nucleus accumbens

Elevated dopamine levels are believed to contribute to the rewarding sensation of ethanol (EtOH), and previous research has shown that strychnine‐sensitive glycine receptors in the nucleus accumbens (nAc) are involved in regulating dopamine release and in mediating the reinforcing effects of EtOH. Furthermore, the osmoregulator taurine, which is released from astrocytes treated with EtOH, can act as an endogenous ligand for the glycine receptor, and increase extracellular dopamine levels. The aim of this study was to address if EtOH‐induced swelling of astrocytes could contribute to elevated dopamine levels by increasing the extracellular concentration of taurine. Cell swelling was estimated by optical sectioning of fluorescently labeled astrocytes in primary cultures from rat, and showed that EtOH (25–150 mM) increased astrocyte cell volumes in a concentration‐ and ion‐dependent manner. The EtOH‐induced cell swelling was inhibited in cultures treated with the Na+/K+/2Cl‐ cotransporter blocker furosemide (1 mM), Na+/K+‐ATPase inhibitor ouabain (0.1 mM), potassium channel inhibitor BaCl2 (50 µM) and in cultures containing low extracellular sodium concentration (3 mM). In vivo microdialysis performed in the nAc of awake and freely moving rats showed that local treatment with EtOH enhanced the concentrations of dopamine and taurine in the microdialysate, while glycine and β‐alanine levels were not significantly modulated. EtOH‐induced dopamine release was antagonized by local treatment with the glycine receptor antagonist strychnine (20 µM) or furosemide (100 µM or 1 mM). Furosemide also prevented EtOH‐induced taurine release in the nAc. In conclusion, our data suggest that extracellular concentrations of dopamine and taurine are interconnected and that swelling of astrocytes contributes to the acute rewarding sensation of EtOH.

A scoring system for antenatal identification of fetal growth retardation

Summary. A scoring system for selection of pregnancies at risk of intrauterine growth retardation (IUGR) is presented. It is based on eight weighted items which include information from previous pregnancies and from the current one including the increment of fundal height and of maternal weight. With a risk population of 7% all IUGR infants were included. The IUGR infants constituted 34% of the risk group.

Cell swelling, seizures and spreading depression: An impedance study

The cellular processes that take place during the transition from pre-seizure state to seizure remain to be defined. In this study in awake, paralyzed rats, we used an electrical impedance measure of changes in extra-cellular intracranial volume to estimate changes in cell size in acute models of epilepsy. Animals were prepared with extradural electroencephalographic (EEG)/impedance electrodes and a venous catheter. On a subsequent day, animals were paralyzed, ventilated and treated with picrotoxin, kainic acid or fluorocitrate in doses that usually induce epileptiform discharges. We now report that increases in baseline impedance were induced by kainic acid and smaller increases by picrotoxin. We also demonstrated that epileptiform discharges were preceded by small, accelerated increases in impedance. Increases in baseline impedance were highly correlated with increases in power of non-ictal high frequency EEG activity. Seizures were accompanied by increases in impedance and all treatments induced transient, relatively large, increases in impedance often associated with unilateral reductions in low frequency EEG, likely periods of spreading depression. We conclude: cerebral cells swell in convulsant models of epilepsy, that there are pre-ictal accelerations in cell swelling, and that spreading depression-like events are frequently associated with seizures.