Plastic Change along the Intact Crossed Pathway in Acute Phase of Cerebral Ischemia Revealed by Optical Intrinsic Signal Imaging

The intact crossed pathway via which the contralesional hemisphere responds to the ipsilesional somatosensory input has shown to be affected by unilateral stroke. The aim of this study was to investigate the plasticity of the intact crossed pathway in response to different intensities of stimulation in a rodent photothrombotic stroke model. Using optical intrinsic signal imaging, an overall increase of the contralesional cortical response was observed in the acute phase (≤48 hours) after stroke. In particular, the contralesional hyperactivation is more prominent under weak stimulations, while a strong stimulation would even elicit a depressed response. The results suggest a distinct stimulation-response pattern along the intact crossed pathway after stroke. We speculate that the contralesional hyperactivation under weak stimulations was due to the reorganization for compensatory response to the weak ipsilateral somatosensory input.

Chronic ventricular myocyte-specific overexpression of angiotensin II type 2 receptor results in intrinsic myocyte contractile dysfunction

ANG II type 2 receptor (AT2) is upregulated in failing hearts, but its effect on myocyte contractile function is not known. We measured fractional cell shortening and intracellular Ca2+ concentration transients in left ventricular myocytes derived from transgenic mice in which ventricle-specific expression of AT2 was driven by the myosin light chain 2v promoter. Confocal microscopy studies confirmed upregulation of AT2 in the ventricular myocytes and partial colocalization of AT2 with AT1. Three components of contractile performance were studied. First, baseline measurements (0.5 Hz, 1.5 mmol/l extracellular Ca2+ concentration, 25°C) and study of contractile reserve at faster pacing rates (1–5 Hz) revealed Ca2+-dependent contractile dysfunction in myocytes from AT2 transgenic mice. Comparison of two transgenic lines suggested a dose-dependent relationship between magnitude of contractile dysfunction and level of AT2 expression. Second, activity of the Na+/H+ exchanger, a dominant transporter that regulates beat-to-beat intracellular pH, was impaired in the transgenic myocytes. Third, the inotropic response to β-adrenergic versus ANG II stimulation differed. Both lines showed impaired contractile response to β-adrenergic stimulation. ANG II elicited an increase in contractility and intracellular Ca2+ in wild-type myocytes but caused a negative inotropic effect in myocytes from AT2 transgenic mice. In contrast with β-adrenergic response, the depressed response to ANG II was related to level of AT2 overexpression. The depressed response to ANG II was also present in myocytes from young transgenic mice before development of heart failure. Thus chronic overexpression of AT2 has the potential to cause Ca2+- and pH-dependent contractile dysfunction in ventricular myocytes, as well as loss of the inotropic response to ANG II.

Adult carotid chemoafferent responses to hypoxia after 1, 2, and 4 wk of postnatal hyperoxia

Exposing newborn rats to postnatal hyperoxia (60% O2) for 1-4 wk attenuates the ventilatory and phrenic nerve responses to acute hypoxia in adult rats. The goal of this research was to increase our understanding of the carotid chemoreceptor afferent neural input in this depressed response with different durations of postnatal hyperoxic exposure. Rats were exposed from a few days before birth to 1, 2, or 4 wk of 60% O2 and studied after 3-5 mo in normoxia. The rats were anesthetized with urethane. Whole carotid sinus nerve (CSN) responses to NaCN (40 μg/kg iv), 10 s of asphyxia and acute isocapnic hypoxia (arterial Po2 45 Torr) were determined. Mean CSN responses to stimuli after postnatal hyperoxia were reduced compared with controls. Responses in rats exposed to 1 wk of postnatal hyperoxia were less affected than those exposed to 2 and 4 wk of hyperoxia, which were equivalent to each other. These studies illustrate the importance of normoxia during the first 2 wk of life in development of carotid chemoreceptor afferent function.

Specific immunosuppression byTrichinella: fine specificity and effect on lymphocyte functionin vivo

Muscle-phaseTrichinellalarvae depress the immune response of mice to the phosphorylcholine (PC)-bearingTrichinellaantigen FCp without affecting responses to other PC-bearing or non-PC antigens. The depressive activity is independent of antigen dose andTrichinellaspecies and, in adoptive cell transfer experiments with lethally irradiated recipient mice, depended on the state of the recipient (infected recipients had a depressed response even a month after their encysted larvae had been killed and regardless of whether the donor had been exposed to FCp) but not on the state of the transferred cells. We conclude that lymphocytes are not permanently altered by the depressive action, that the agent responsible persists in the host at least a month after the death of the encystedTrichinellalarvae, and that the alteration does not eliminate lymphocyte immunological memory.

REFRACTORINESS OF THE PITUITARY GLAND AFTER CONTINUOUS EXPOSURE TO LUTEINIZING HORMONE RELEASING HORMONE

The refractoriness of LH release by pituitary glands from intact female rats was studied during stimulation by luteinizing hormone releasing hormone (LH-RH), monobutyryl cyclic AMP+theophylline or potassium in vitro. Various concentrations of LH-RH (0·1, 0·3 and 10 ng/ml) all caused refractoriness within 24 h. Subsequent exposure to a supramaximally active concentration of LH-RH for 6 h also resulted in a depressed response; the degree of inhibition depended on the concentration of LH-RH to which the glands had been exposed previously. Glands made refractory to LH-RH also showed a depressed response to monobutyryl cyclic AMP+theophylline, although these agents by themselves were unable to induce refractoriness. Incubation in medium containing a high concentration of potassium also resulted in the release of LH, which in all respects was similar to that caused by LH-RH. Glands made refractory to LH-RH showed a decreased response to potassium and, conversely, the release of LH in response to LH-RH was reduced after exposure of glands to potassium. It is concluded that the LH releasing activity of LH-RH, which is mimicked by potassium, deteriorates during continuous exposure to the secretagogue.