Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption

Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor.     

Conus medullaris injury following both tetracaine and lidocaine spinal anesthesia

Multiple reports of cauda equina syndrome and transient radicular nerve root irritation have suggested that lidocaine spinal anesthesia may be responsible. In this case report, a patient with a preexisting diabetic neuropathy received a partial block following a tetracaine spinal, which was followed by a lidocaine spinal. Following block resolution, a new conus medullaris syndrome was diagnosed. Because of the close proximity of the cauda equina and the conus medullaris, differentiation between these syndromes can be difficult. The preexisting diabetic neuropathy may have predisposed this patient to neurologic injury. The choice of a different local anesthetic drug with less neurotoxic potential such as bupivacaine may have prevented this injury.     

Fine mapping of the spatial relationship between acute ischemia and dendritic structure indicates selective vulnerability of layer V neuron dendritic tufts within single neurons in vivo.

We have evaluated the spatial relationship between clotted vasculature and the structural integrity of layer V cortical neurons in YFP (yellow fluorescent protein)-H transgenic mice 2 to 10 h after photothrombotic stroke. Fortuitously, ischemic zones could be finely mapped about dysmorphic YFP labeled axons and dendrites using histology since Texas-red dextran used to assess blood flow in vivo was trapped within fixed clotted vessels. Ischemic damage to layer V neurons located at the border of ischemia was contained within apical tuft spiny dendritic structures and did not propagate to spines on the more proximal region of the apical dendrite. The lateral spread of dendritic damage decayed sharply with distance from the edge of ischemia (50% reduction in beaded dendrites within approximately 100 microm) and increased with time up to 6 h after stroke but not thereafter. Axonal damage also increased with time but extended further laterally than dendritic damage, up to 500 microm from the stroke core. Apoptotic and necrotic cell death cascades were activated 6 h after stroke; however, only within 300 microm of the ischemic core. These data suggest that the axonal and dendritic circuitry of neurons located 300 microm outside of an ischemic zone can be relatively free of damage or commitment to cell death suggesting that they may be in an ideal position to contribute to functional recovery. Given that ischemic damage may have a larger effect on circuitry involving superficial dendrites and projecting axons, it is conceivable that surviving peri-infarct neurons may have unique structural and functional properties.     

Molecular cytogenetic characterization of Thinopyrum and wheat--Thinopyrum translocated chromosomes in a wheat--Thinopyrum amphiploid

The wheat--Thinopyrum amphiploid 'Agrotriticum # 3425' (AT 3425), which is highly resistant to Cephalosporium stripe, was identified to carry seven pairs of Thinopyrum chromosomes, three pairs of wheat--Thinopyrum translocated chromosomes and 18 pairs of wheat chromosomes. Fluorescence genomic in situ hybridization (FGISH), C-banding, sequential C-banding and FGISH, and denaturing polyacrylamide gel electrophoresis (SDS-PAGE) were used to characterize and identify the chromosomes. The Thinopyrum chromosomes in AT 3425 were designated as T1 through T7 based on their C-banding patterns. The FGISH and C-banding patterns of mitotic chromosomes in AT 3425 and meiotic chromosomes in the hybrid between AT 3425 and wheat cultivar 'Chinese Spring' (CS) revealed that wheat chromosomes 1D, 2B and 3D were involved in the three wheat-Thinopyrum chromosome translocations designated as (W-T)1, (W-T)2, and (W-T)3 respectively. The analysis of high-molecular-weight glutenin subunits in single seeds of AT 3425 confirmed the involvement of wheat chromosome 1D in the translocation (W-T)1. The designations 1DSuu.1DL-1TL, 2BSuu.2BL-2TL and 3DSuu.3DL-3TL were suggested for the wheat--Thinopyrum translocated chromosomes (W-T)1, (W-T)2 and (W-T)3 in AT 3425 respectively.     

Transnasal jet ventilation is a useful adjunct to teach fibreoptic intubation: a preliminary report

PURPOSE: Fibreoptic intubation (FOI) has become an essential technique in the anesthetic management of patients with difficult airways. Unfortunately, residents may graduate from anesthesiology training programs with insufficient skills in FOI. To enhance resident proficiency at FOI without compromising patient comfort or safety, the technique of transnasal jet ventilation-assisted FOI was developed. This report describes our initial experience with this technique. METHODS: Sixty-four patients scheduled for oromaxillofacial surgery under nasal endotracheal anesthesia were recruited. Twenty-eight residents at all levels of training performed FOI through the patient's right nostril after the induction of general anesthesia and neuromuscular blockade. Oxygenation and ventilation were maintained by a faculty anesthesiologist using a Sanders device to deliver a jet of oxygen through a nasal trumpet placed in the patient's left nostril. The time from induction until completion of the FOI was recorded. Residents were subsequently queried about the educational benefit of the technique using a standardized questionnaire. RESULTS: All residents were able to successfully intubate all patients in this study. Thirteen residents successfully performed intubations on three or more occasions with 70% performing the technique faster on the third trial than on the first. No evidence of hypoxemia, gastric distension, pneumothorax, hemodynamic instability or recall was observed. All respondents to the questionnaire reported that the technique was useful as an educational tool and recommended its use with other residents. CONCLUSION: Transnasal jet ventilation-assisted FOI is a useful method to train residents in FOI while maximizing patient comfort and safety.     

Respiratory airway changes in response to suggestion in normal individuals

Thirty normal individuals were told they were inhaling a substance that would either cause breathing difficulty (N = 15) or not affect breathing (N = 15). Total respiratory resistance was measured prior to and during inhalation. In reality, the subjects inhaled no substance; inhalation consisted of breathing normally into a respiratory resistance recorder. Individuals who received the former suggestion exhibited increased total respiratory resistance during inhalation, whereas individuals who received the latter suggestion did not. These observations demonstrated that the ability of suggestion to affect the respiratory airway is not limited to asthmatic individuals.     

The intravascular contribution to fmri signal change: monte carlo modeling and diffusion-weighted studies in vivo

Understanding the relationship between fMRI signal changes and activated cortex is paramount to successful mapping of neuronal activity. To this end, the relative extravascular and intravascular contribution to fMRI signal change from capillaries (localized), venules (less localized) and macrovessels (remote, draining veins) must be determined. In this work, the authors assessed both the extravascular and intravascular contribution to blood oxygenation level-dependent gradient echo signal change at 1.5 T by using a Monte Carlo model for susceptibility-based contrast in conjunction with a physiological model for neuronal activation-induced changes in oxygenation and vascular volume fraction. The authors compared our Model results with experimental fMRI signal changes with and without velocity sensitization via bipolar gradients to null the intravascular signal. The model and experimental results are in agreement and suggest that the intravascular spins account for the majority of fMRI signal change on T₂^*-weighted images at 1.5 T.     

Chronic brief restraint decreases in vivo binding of benzodiazepine receptor ligand to mouse brain

This study examines the effects of chronic brief restraint on in vivo benzodiazepine (BZD) receptor binding in mouse brain. Three groups of mice were used. Mice in group 1 were neither restrained nor injected (ACUTE control). Mice in group 2 were restrained for 5–6 s by grabbing the back skin and holding the subject upside-down at a 45° angle as if to be injected (CHRONIC SHAM control) for 7 d. Mice in group 3 (CHRONIC SALINE) received daily single intraperitoneal (ip) injections of saline (5 mL/kg) for 7 d. On d 8 BZD receptors were labeled in vivo by administration of 3 μCi [³H]flumazenil (ip). The levels of ligand bound in vivo to cerebral cortex (CX), cerebellum (CB), brain stem (BS), striatum (ST), hippocampus (HP), and hypothalamus (HY) were determined. Results indicated that the level of binding was significantly (p<0.01) lower by 30–50% (depending on the brain region) in saline-injected or sham control groups compared to acute control animals. Furthermore, the values for sham control were similar to the saline-treated group. Our data suggest that exposure to chronic mild restraint produces a decrease in in vivo binding of [³H]flumazenil in mouse brain and supports the hypothesis that chronic mild stress produces a decrease in BZD receptor binding sites.