ABSTRACT
Cardiopulmonary exercise testing (CPET) is used as a risk stratification tool for patients undergoing major surgery. In this study, we investigated the role of CPET in predicting day five cardiopulmonary morbidity in patients undergoing head and neck surgery. This observational cohort study included 230 adults. We recorded preoperative CPET variables and day five postoperative cardiopulmonary morbidity. Full data from 187 patients were analysed; 43 patients either had incomplete data sets or declined surgery/CPET. One hundred and nineteen patients (63.6%) developed cardiopulmonary morbidity at day five. Increased preoperative heart rate and duration of surgery were independently associated with day five cardiopulmonary morbidity. Those with such morbidity also had lower peak VÌO2 11.4 (IQR 8.4-18.0) vs 16.0 (IQR 14.0-19.7) ml.kg-1.min-1, P<0.0001 and VÌO2 at AT 10.6 (IQR 9.1-13.1) vs 11.5 (IQR 10.5-13.0) ml.kg-1.min-1, p=0.03. Logistic regression model containing peak VÌO2 and duration of surgery demonstrated that increased peak VÌO2 was associated with a reduction in the likelihood of cardiopulmonary complications OR 0.92 (95%CI 0.87 to 0.96), p=0.001. The area under the receiver operating characteristic curve for this model was 0.75(95%CI 0.68 to 0.82), p<0.0001, 64% sensitivity, 81% specificity. CPET can help to predict day five cardiopulmonary morbidity in the patients undergoing head and neck surgery. A model containing peak VÌO2 allowed identification of those with such complications.
Subject(s)
Exercise Test , Postoperative Complications , Adult , Humans , Logistic Models , Morbidity , Oxygen Consumption , Postoperative Complications/epidemiology , ROC CurveABSTRACT
Cancer in the transplanted kidney is rare, and its clinical and surgical management can be controversial. We report 3 cases of cancer in renal transplantation (1 case of renal cell carcinoma and 2 cases of transitional cell carcinoma) and their treatment. Our data and those reported in the literature suggest that these cancers can be treated like a neoplasm in the general population. However, a higher number of cases and longer follow-up periods are necessary to confirm our findings.
Subject(s)
Carcinoma, Renal Cell , Carcinoma, Transitional Cell , Kidney Transplantation , Postoperative Complications , Adult , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/surgery , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/surgery , Humans , Male , Middle Aged , Postoperative Complications/diagnosis , Postoperative Complications/surgerySubject(s)
Neoplasms/blood , Prothrombin Time/instrumentation , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle AgedABSTRACT
Resazurin is a dye, which becomes fluorescent when reduced by oxidoreductases within viable cells. Measurement of resazurin fluorescence is therefore an indicator of the cell's energy metabolism. Resazurin was used here to detect metabolic changes in PC12 cells following serum starvation. Serum withdrawal is a cytotoxic environmental change resulting in cell death in cultured cell lines as well as in primary cells of various tissue origins, including nerve cells. In particular, PC12 cells have been widely employed as a neuronal cell model and a large number of studies generated. Many molecular and morphological changes occur in PC12 cells after serum withdrawal, and apoptotic cell death is the final consequence. We show that resazurin can detect the metabolic impairment in serum-deprived PC12 cells and can measure the neuroprotective properties of PACAP 1-38, as early as day 1 after serum withdrawal. Resazurin constitutes an advantageous tool to discriminate between healthy and metabolically impaired cells, since fluorescence produced by the reduced dye can be measured in living cells without a lysis step. The experiment is fast, inexpensive, uses a small amount of cells and can easily be automated.
Subject(s)
Culture Media, Serum-Free/pharmacology , Energy Metabolism/drug effects , Indicators and Reagents , Neurons/metabolism , Neuropeptides/pharmacology , Neuroprotective Agents/pharmacology , Oxazines , Peptide Fragments/pharmacology , Xanthenes , Animals , Cell Survival/drug effects , Microscopy, Fluorescence/methods , Microscopy, Phase-Contrast/methods , Neurons/drug effects , PC12 Cells , Pituitary Adenylate Cyclase-Activating Polypeptide , RatsABSTRACT
The aim of this study was to investigate the extracellular matrix gene expression in the hypertrophied left ventricular tissue of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, at early and mature ages. Interestingly, with age, a marked increase (+85% and +187% at 25 and 30 weeks of age, respectively, p < 0.01, vs 5 weeks) in matrix metalloproteinase-1 (MMP-1) mRNA levels in SHR and a progressive decrease (-50%, -70%, -78%, -70% at 10, 15, 25 and 30 weeks, respectively, p < 0.01, vs 5 weeks) in WKY were seen. Moreover, mRNA levels were significantly lower in SHR at 5 weeks. The analysis of mRNA expression for the tissue inhibitor of metalloproteinase-1 (TIMP-1) showed a significant increase in WKY (+44% and +44%, vs 15 and 25 weeks, respectively, p < 0.05), whereas there were no significant changes in SHR with development. At 30 weeks TIMP-1 mRNA levels were significantly reduced in SHR. Temporal trends of procollagen alpha1(I) and procollagen alpha1(III) mRNA levels were similar in both strains, but lower levels for procollagen alpha1(III) were found in SHR at 5 and 30 weeks. Although no significant differences were measured between the strains, mRNA levels for fibronectin were found decreased in WKY and increased in SHR with age. The results of the present study suggest an altered balance between collagen deposition and collagen degradation with development in this model of left ventricular hypertrophy and hypertension.
Subject(s)
Extracellular Matrix/genetics , Hypertension/metabolism , Aging/physiology , Animals , Collagenases/analysis , Collagenases/genetics , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Gene Expression , Hypertension/genetics , Hypertrophy, Left Ventricular/metabolism , Male , Matrix Metalloproteinase 1 , Procollagen/analysis , Procollagen/genetics , RNA, Messenger/analysis , Rats , Rats, Inbred SHR , Rats, Inbred WKYABSTRACT
Stress-activated protein kinase/extracellular signal-regulated protein kinase-1/c-Jun NH2-terminal kinase kinase is a dual-specificity kinase which phosphorylates and activates stress-activated protein kinase/c-Jun NH2-terminal kinase, a recently discovered mitogen-activated protein kinase that is stimulated by stressful stimuli and that regulates cellular transcriptional activity. The distribution of the messenger RNA encoding for stress-activated protein kinase/extracellular signal-regulated protein kinase-1 was evaluated in the adult and developing rat central nervous system. In situ hybridization with a 35S-labelled 45mer oligodeoxynucleotide probe was used to map the distribution of the stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA in postnatal day 1, 3, 6, 9, 12, 15, 18, 21 and adult rat brains. Specific labelling was generally associated with neuronal profiles. In the adult central nervous system, high hybridization signals were observed in the hippocampus, the granular layer of the cerebellum, the medial habenula, the anterodorsal thalamic nucleus, the red nucleus, the pontine nuclei, the facial nucleus, the motor and mesencephalic nuclei of the trigeminal nerve, the hypoglossal nucleus, the vestibular nucleus and the nucleus ambiguus. Intermediate levels were present in diencephalic and mesencephalic regions and in the neocortex, while basal ganglia displayed a low hybridization signal. In the developing brain, the heterogeneous distribution of the hybridization signal observed in the adult brain was already present, but in the hippocampus and basal ganglia the stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA levels were significantly higher at postnatal day 3 and during the second postnatal week than in the adult. The results show that stress-activated protein kinase/extracellular signal-regulated protein kinase-1 is widely expressed in the rat central nervous system and co-localizes with its substrate stress-activated protein kinase. The observed changes in stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA levels during postnatal development suggest a role for this protein in the maturation of brain circuits.
Subject(s)
Brain/growth & development , Brain/metabolism , Phosphotransferases/metabolism , Proto-Oncogene Proteins c-jun/metabolism , Animals , Base Sequence , Female , In Situ Hybridization , Male , Molecular Sequence Data , Pregnancy , RNA, Messenger/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
Calcium is essential for a variety of functions in animals, including signal transduction, transmission of nerve impulses, and bone and scale growth. In freshwater adapted teleosts, blood calcium levels are maintained constant (2-4 mM) even at low external calcium concentration (< 0.01 mM). Epithelial cells in skin and gill have been implicated in calcium homeostasis. We have cloned a cDNA from Ictalurus punctatus, the channel catfish, that codes for ictacalcin, a novel member of the S100 family of calcium-binding protein. In-situ hybridization demonstrates ictacalcin mRNA is abundant in epithelial cells of olfactory rosette, barbel, skin and gill but not brain or muscle. The presence of ictacalcin protein in these tissues was confirmed by immuno-blot analysis. Tissue extracts and recombinant ictacalcin bind calcium with attendant changes in electrophoretic mobility indicative of changes in protein conformation. The calcium-binding activity and abundant localization of ictacalcin in epithelial cells of several tissues indicates that this protein plays an important role in catfish calcium homeostasis.
Subject(s)
Calcium-Binding Proteins/genetics , Ictaluridae/genetics , Transcription Factors/genetics , Amino Acid Sequence , Animals , Base Sequence , Calcium/metabolism , Calcium-Binding Proteins/chemistry , Calcium-Binding Proteins/isolation & purification , Chemoreceptor Cells/metabolism , Cloning, Molecular , DNA, Complementary/genetics , Epidermis/metabolism , Gills/metabolism , Ictaluridae/metabolism , In Situ Hybridization , Molecular Sequence Data , Multigene Family , Nerve Tissue Proteins/metabolism , Olfactory Pathways/metabolism , Organ Specificity , Protein Conformation , RNA, Messenger/analysis , Receptors, Cell Surface , Recombinant Fusion Proteins/metabolism , Transcription Factors/chemistry , Transcription Factors/isolation & purificationABSTRACT
Mitogen-activated protein kinases are important mediators of signal transduction from the cell surface to the nucleus and their activation has been implicated in a wide array of physiological processes. The extracellular-signal-regulated kinases are the archetypal and best studied members of the mitogen activated protein kinases. Recently, additional subgroups of mitogen activated protein kinases have been identified which exhibit distinct regulatory elements, substrate specificity and respond to diverse extracellular stimuli. Among these newly identified protein kinases are the rat stress-activated protein kinases. Despite a rapidly expanding literature on the biochemical properties of stress-activated protein kinases no anatomical data are yet available. In the present study, we have investigated the regional distribution of messenger RNA transcripts for stress-activated protein kinases in the adult rat central nervous system and compared this distribution to that observed for extracellular-signal-regulated kinases. Intense labelling for stress-activated protein kinases could be detected in discrete brain areas with high levels in hippocampus, neocortex and some nuclei of the brain stem. The apparent hybridization signal appeared to be selectively neuronal. Stress-activated protein kinases and extracellular-signal-regulated kinases hybridization patterns appeared generally dissimilar although a certain degree of co-expression in some brain areas, such as the hippocampal formation, could be observed. These results reveal an extreme complexity in the mitogen-activated protein kinase signalling pathway and suggest the existence of parallel mitogen-activated protein kinase cascades that can be activated independently or in some cases simultaneously, by extracellular stimuli.
Subject(s)
Brain/metabolism , Mitogens/pharmacology , Protein Kinases/metabolism , RNA, Messenger/metabolism , Animals , Autoradiography , Histocytochemistry , In Situ Hybridization , Rats , Rats, Sprague-Dawley , Signal TransductionABSTRACT
Expressed sequence tags (ESTs) for the catfish (Ictalurus punctatus) were identified and characterized by shotgun sequencing coupled to Northern analysis. We have identified and characterized a number of cDNA clones from a catfish olfactory mucosal library that show differential tissue expression including several that are enriched in chemosensory tissue. Among the novel cDNA clones studied were an olfactory specific beta-tubulin and a novel member of the S-100 family of calcium-binding proteins that is highly expressed in barbel, olfactory mucosa and gill, but not in brain. Several clones of low abundance mRNAs were also identified, including one manifesting a basic-helix-loop-helix (b-HLH) motif that is typical of many transcription factors. Additional cDNA clones whose mRNAs are differentially expressed, but are of unknown function, were also obtained. These results demonstrate the case with which novel gene products enriched in chemosensory tissues can be identified.
Subject(s)
Cell Cycle Proteins , DNA, Complementary/analysis , Ictaluridae/genetics , Nerve Tissue Proteins/genetics , Olfactory Mucosa/metabolism , S100 Proteins , Amino Acid Sequence , Animals , Base Sequence , Blotting, Northern , Brain/metabolism , Calcium-Binding Proteins/biosynthesis , Calcium-Binding Proteins/genetics , Cloning, Molecular , Creatine Kinase/genetics , Enhancer Elements, Genetic , Gene Expression , Gene Library , Gills/metabolism , Helix-Loop-Helix Motifs , Mice , Molecular Sequence Data , Nerve Tissue Proteins/biosynthesis , Olfactory Receptor Neurons/metabolism , Oligodeoxyribonucleotides , Plasmids , RNA, Messenger/biosynthesis , RNA, Messenger/metabolism , S100 Calcium Binding Protein A6 , Sequence Homology, Amino Acid , Transcription Factors/biosynthesis , Transcription Factors/genetics , Tubulin/biosynthesis , Tubulin/geneticsABSTRACT
The necessary theoretical considerations for the development of a correct quantitative analysis of a low abundance messenger RNA (mRNA), estrogen receptor mRNA, by competitive polymerase chain reaction (PCR) are presented together with a series of experimental data. When compared to other methodologies currently utilized for RNA quantitation, this PCR application proved to be a very reliable, rapid and sensitive method. Furthermore, the PCR-based quantitative method described is of particular interest since it does not require the use of radiolabeled compounds.
Subject(s)
Polymerase Chain Reaction/methods , RNA, Messenger/analysis , Receptors, Estrogen/genetics , Animals , Base Sequence , Brain/metabolism , DNA, Complementary/biosynthesis , Female , Models, Theoretical , Molecular Sequence Data , Rats , Uterus/metabolismABSTRACT
The cDNA of the Sprague-Dawley rat estrogen receptor was sequenced. With respect to the published Wistar rat estrogen receptor sequence, a single amino acid difference (tryptophan instead of asparagine) was found in the hormone binding site. Since tryptophan was found at the same position in chicken, human and mouse estrogen receptors, it is proposed that the Wistar rat could represent an interesting natural mutant for estrogen receptor studies.
Subject(s)
Receptors, Estrogen/genetics , Amino Acid Sequence , Animals , Base Sequence , DNA/analysis , Estradiol/pharmacology , Female , Molecular Sequence Data , Polymerase Chain Reaction , Rats , Rats, Sprague-Dawley , Rats, Wistar , TritiumABSTRACT
A series of studies was done in order to fully characterize the estrogen receptor (ER) expressed in the hippocampus of adult female rat. The structural identity among the ER mRNAs expressed in the hippocampus, hypothalamus and uterus was established by polymerase chain reaction amplification of the ER cDNA. Subsequently, the ER of the hippocampus was proved to bind DNA and beta-estradiol with the same affinity as the hypothalamic receptor. Finally, it was demonstrated that systemic administration of beta-estradiol determines the nuclear increase of ER levels with a time course which appears to be almost superimposable in the hippocampus and hypothalamus. On the basis of the above-mentioned evidence, it is concluded that the ER expressed in the hippocampus is structurally and functionally indistinguishable from the receptor expressed in the other hormone target tissues.
Subject(s)
Cell Nucleus/drug effects , DNA-Binding Proteins/metabolism , Hippocampus/chemistry , Nerve Tissue Proteins/analysis , Receptors, Estrogen/analysis , Transcription, Genetic/genetics , Animals , Base Sequence , Cell Nucleus/metabolism , DNA/chemical synthesis , Estradiol/metabolism , Estradiol/pharmacology , Female , Immunoenzyme Techniques , Molecular Sequence Data , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Polymerase Chain Reaction , Rats , Rats, Sprague-Dawley , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Sensitivity and SpecificityABSTRACT
Differential screening of a cDNA library prepared from mRNA of the hippocampus of estrogen-stimulated ovariectomized female rats led to the identification of a single estrogen-induced clone. Analysis of the sequence identified this cDNA as the gene coding for subunit III of the enzyme cytochrome c oxidase. Cytochrome c oxidase subunit III mRNA levels significantly increased as early as 3 h following the administration of a single dose of hormone. This effect was visible in the hippocampus and in the hypothalamus, but not in the other brain areas examined. Because subunit III of the cytochrome c oxidase is of mitochondrial origin, the mechanism involved in the estrogenic effect is still unknown. The observation that the activity of cytochrome c oxidase can also be induced by estrogens in the hippocampus indicates that this induction may be secondary to the increased expression of the other subunits of cytochrome c oxidase or to the general increase of neuronal activity.
Subject(s)
Electron Transport Complex IV/metabolism , Estradiol/pharmacology , Amino Acid Sequence , Animals , Autoradiography , Base Sequence , Electron Transport Complex IV/chemistry , Electron Transport Complex IV/genetics , Enzyme Induction , Female , Hippocampus/enzymology , Molecular Sequence Data , RNA/metabolism , Rats , Rats, Inbred StrainsABSTRACT
A rapid and highly reproducible protocol which permits the detection of quantities of estrogen receptor as low as 5 fmol/mg protein is described. The separation of free and receptor-bound hormone is achieved by specific immunoprecipitation of the hormone-receptor complex. This procedure can be performed without perturbing the equilibrium of the binding reaction.
Subject(s)
Receptors, Estrogen/analysis , Animals , Cytosol/chemistry , Female , Mice , Rats , Rats, Inbred Strains , Receptors, Estrogen/immunology , Reproducibility of ResultsABSTRACT
The identification of estrogen-inducible genes in specific regions of the central nervous system (CNS) will give information about the mechanisms by which this steroid modulates nervous activity. Two-dimensional gel analysis of the proteins synthesized in vitro from mRNA isolated from control or estrogen-treated rats indicated that the levels of mRNA were increased in the estrogen-treated animals. The levels of mRNA were elevated only in those brain regions that express estrogen receptors.
Subject(s)
Estrogens/pharmacology , Hypothalamus/metabolism , Nerve Tissue Proteins/biosynthesis , Animals , Autoradiography , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Densitometry , Female , Hypothalamus/drug effects , Isoelectric Focusing , Molecular Weight , Protein Biosynthesis , RNA, Messenger/isolation & purification , Rats , Rats, Inbred StrainsABSTRACT
Quantitative autoradiographic analysis revealed changes in [3H]flunitrazepam (a benzodiazepine agonist) binding in the anterior hypothalamus nucleus, the medial preoptic area and the cortico-medial amygdala nucleus following in vivo estradiol. The administration of 4 mg of progesterone, but not 1 mg, increased the binding of [3H]flunitrazepam in the basolateral amygdaloid nucleus and in the oriens-pyramidalis CA1 layer of the hippocampus. Exposure of brain sections in vitro to the potent, naturally occurring progesterone metabolite, 3 alpha-hydroxy-5 alpha-dihydroprogesterone, induced GABA-dependent changes in flunitrazepam binding, similar to the changes induced by progesterone, thus suggesting that different steroid mechanisms are implicated in the control of flunitrazepam binding.
Subject(s)
Brain/metabolism , Flunitrazepam/metabolism , Gonadal Steroid Hormones/pharmacology , Animals , Autoradiography , Brain/drug effects , Estradiol/pharmacology , Female , Ovariectomy , Progesterone/pharmacology , Rats , Rats, Inbred StrainsABSTRACT
An analysis of the distribution of estrogen receptor (ER) via immunoenzymatic assay in the brain of ovariectomized rats reveals the presence of large amounts of ER-like immunoreactive material in the cytosol of the hippocampus: a brain area described to contain little estrogen-binding activity. The protein detected in the hippocampus by the specific antibody is indistinguishable from the rat ER in its response to hormonal treatments and in its electrophoretic mobility. The presence of elevated amounts of ER in such an important part of the limbic system creates new possibilities for interpreting the role played by this sex hormone in the central nervous system of rat.
Subject(s)
Hippocampus/analysis , Receptors, Estrogen/analysis , Animals , Blotting, Northern , Blotting, Western , Brain Chemistry , Female , Immunoenzyme Techniques , Poly A/analysis , RNA/analysis , RNA, Messenger , Rats , Uterus/analysisABSTRACT
l-Fenfluramine (l-F) was studied for its ability to release dopamine (DA) and its metabolites in freely moving rats through the trans-striatal dialysis technique. l-F's effect on striatal DA release was also studied in animals made tolerant to the effect of haloperidol by chronic treatment (1 mg/kg i.p. twice daily for 11 days and 48 hr wash-out) with the neuroleptic or pretreated with 300 mg/kg i.p. gamma-butyrolactone (GBL). Five and 10 mg/kg l-F dose-dependently increased the release of DA and its metabolites with a pattern of effects similar to that observed with neuroleptic drugs. The dose of 20 mg/kg l-F had the same effect as 10 mg/kg. Repeated haloperidol treatment reduced the basal release of DA and its metabolites and a much smaller amount of DA and metabolites was released by l-F (10 mg/kg i.p.) and haloperidol (0.1 mg/kg i.p.) in animals treated with haloperidol than in controls. GBL 300 mg/kg i.p. reduced basal DA release by about 50%. When 10 mg/kg l-F, 0.1 mg/kg haloperidol and 0.25 mg/kg d-amphetamine were injected i.p. 40 min after GBL, l-F and haloperidol did not significantly raise DA release in GBL-treated rats whereas a significant effect was observed at various times after d-amphetamine. The data show that l-F resembles haloperidol in its ability to release DA and its metabolites from the corpus striatum of freely moving rats. The cross-tolerance between haloperidol and l-F for their effect on DA release suggests that a common site is involved in the mechanism of these drugs.
Subject(s)
Corpus Striatum/drug effects , Dopamine/metabolism , Fenfluramine/pharmacology , 3,4-Dihydroxyphenylacetic Acid/metabolism , 4-Butyrolactone/pharmacology , Animals , Antipsychotic Agents/pharmacology , Corpus Striatum/metabolism , Drug Tolerance , Fenfluramine/administration & dosage , Haloperidol/pharmacology , Homovanillic Acid/metabolism , Male , Rats , Receptors, Dopamine/drug effects , Secretory Rate/drug effectsABSTRACT
The main aim of the present study was to find out whether the dynamic characteristics of responses of limb extensor muscles to labyrinth stimulation were modified by the proprioceptive input elicited by appropriate displacements of the corresponding limb extremity. In cats decerebrated at precollicular or intercollicular level, the multiunit EMG activity of the medial head of the triceps brachii was recorded during roll tilt of the animal at the frequency of 0.15 Hz, +/- 10 degrees leading to selective stimulation of labyrinth receptors. This stimulation was then tested several times at regular intervals of 2 to 6 min for several hours while maintaining the ipsilateral forelimb in the horizontal extended position, i.e. with the plantar surface of the foot lying on the tilting table, or during passive flexion of the forepaw in plantar or dorsal direction. In all the experiments in which the forelimb was in the control position, the multiunit EMG responses of the triceps brachii were characterized by an increased activity during side-down tilt of the animal and a decreased activity during side up tilt. These responses were related to animal position and not to the velocity of animal displacement, thus being attributed to stimulation of macular, utricular receptors. Static displacement of limb extremities following plantar flexion of the forepaw greatly decreased the amplitude of the EMG modulation and thus the gain of the first harmonic component of the multiunit EMG responses of the ipsilateral triceps brachii to animal tilt. This reduced gain was due not only to a reduced number of motor units recruited during labyrinth stimulation, but also to a reduced modulation of firing rate of the active motor units, as shown by recording the activity of individual motor units. On the other hand, displacement of the same extremity in the opposite direction, i.e. following dorsiflexion of the forepaw, enhanced the amplitude of the EMG modulation and thus the gain of the multiunit EMG responses of the ipsilateral triceps brachii to animal tilt. This finding was mainly due to an increased recruitment of motor units during side-down tilt, although an increased modulation of the firing rate of individual motor units could not be excluded. In both instances, no changes in the phase angle to the responses were observed. The changes in response gain described above depended on the amount of passive displacement of the forepaw and persisted unmodified throughout the new maintained position.(ABSTRACT TRUNCATED AT 400 WORDS)
Subject(s)
Ear, Inner/physiology , Muscles/physiology , Reflex/physiology , Spinal Cord/physiology , Vestibular Nuclei/physiology , Animals , Cats , Decerebrate State/physiopathology , Efferent Pathways/physiology , Electromyography , Forelimb , Posture , Sensory Receptor Cells/physiologyABSTRACT
Previous experiments had shown that in decerebrate cats activation of limb extensor motoneurons during side-down roll tilt of the animal or side-up neck rotation depends on both an increased discharge of excitatory vestibulospinal (VS) neurons and a reduced discharge of inhibitory reticulospinal (RS) neurons of the medulla, thus leading to disinhibition of limb extensor motoneurons. The present experiments were performed to find out whether the locus coeruleus (LC) complex keeps under its tonic inhibitory control the medullary inhibitory RS neurons and, if so, whether this structure intervenes in the gain regulation of the vestibular and neck reflexes acting on the limb extensor musculature. In precollicular decerebrate cats with good postural rigidity of the four limbs, the amplitude of modulation and thus the response gain of the first harmonic component of multiunit EMG responses of limb extensors to sinusoidal stimulation of labyrinth and neck receptors (at 0.15 Hz, +/- 10 degrees) were quite small in forelimb muscles (triceps brachii) and almost negligible or absent in hindlimb muscles (triceps surae). Electrolytic lesion limited to the LC complex decreased the tonic contraction of limb extensors, but greatly increased in the forelimbs (and brought to the light in the hindlimbs) the response modulation of extensor muscles to the same parameters of labyrinth or neck stimulation. Correspondingly, the response gain increased, but no change in the phase angle of the responses was observed. Both changes in posture, as well as in response gain of the limb extensors to labyrinth and neck stimulation, fully developed some time after the LC lesion. This increase in response gain of the vestibular and neck reflexes acting on the limb extensor muscles did not depend on the decrease in postural activity following the LC lesion, since it was still obtained when an increased static stretch of the extensor muscle following passive flexion of the limb compensated for the reduced EMG activity. Moreover, the slope of the regression line relating the gain of the multiunit EMG response of the triceps brachii to animal tilt with the base frequency greatly increased following lesioning of the LC, thus indicating that for the same background discharge of the muscle the amplitude of modulation, and thus the response gain, increased significantly. The effects described above involved mainly, but not exclusively, the limbs ipsilateral to the side of the lesion.(ABSTRACT TRUNCATED AT 400 WORDS)