Carla E. Cogo

Postural control after a strenuous treadmill exercise

The effect of a strenuous treadmill exercise on body stability and the mechanisms associated with it have been studied with two different experimental protocols. The former investigation was based on stabilometric and metabolic measurements performed in basal condition and after a strenuous treadmill exercise whilst the latter dealt with the study of the early postural response to a 3s-bilateral soleus muscle vibration after the strenuous exercise. Our exercise protocol was able to induce an important generalized metabolic fatigue, as assessed by the obtained peak values in the measured metabolic parameters, and resulting in a short-lasting body destabilization. A linear relationship between sway path and oxygen uptake was found. Thus, the short duration of body instability could be likely due to the quite rapid recovery of oxygen uptake. Further, the fatigue-induced body instability did not associate with changes in the early postural response to soleus muscle vibration. The present study cannot rule out the possibility that further central and/or peripheral mechanisms, influencing the postural control, may play a role in the fatigue-induced changes in body sway.

Effect of microelectrophoretically applied corticosterone on raphe neurones in the rat.

The effect of microelectrophoretic application of corticosterone (CS) on single neurones of raphe nuclei (RN) were investigated in rats under urethane anaesthesia. Ejecting currents generally ranged from 5 to 40 nA. CS produced an excitatory effect in 61% and no effect in 39% of the neurones. None of the 54 neurones studied was inhibited by CS. These quite homogeneous data support the hypothesis that RN are involved in the regulation of most of the nervous functions in which glucocorticoid hormones have been implicated.

Insulin Sensitivity and Glucose Effectiveness Estimated by the Minimal Model Technique in Spontaneously Hypertensive and Normal Rats

This study was performed to compare glucose metabolism in anaesthetised spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) in an attempt to clarify whether this animal model of hypertension approximates the insulin‐resistant state seen in human hypertension. With this aim the minimal model of glucose kinetics was applied to glucose and insulin data derived from a 12‐sample, 120 min intravenous glucose tolerance test (IVGTT) performed in ten SHR and nine WKY rats under pentobarbital anaesthesia. This method provided two metabolic indices: the glucose effectiveness, SG, which quantifies the ability of glucose per se to enhance its rate of disappearance and to inhibit hepatic glucose production, and the insulin sensitivity, SI, which measures the ability of insulin to enhance plasma glucose disappearance and to inhibit hepatic glucose production. Systolic and diastolic arterial pressures in the SHR group were significantly higher (P < 0.0005) than in the WKY group. Mean SG and SI estimates from the SHR group (SG = 16.2 (± 2.0) × 10‐2 dl min‐1 kg‐1 and SI = 12.5 (± 1.9) × 10‐4 dl min‐1 kg‐1 (μU ml‐1)‐1) were not significantly different (P > 0.05) from mean estimates that characterised the WKY group (SG = 13.1 (± 1.5) × 10‐2 dl min‐1 kg‐1 and SI = 15.8 (± 4.3) × 10‐4 dl min‐1 kg‐1 (μU ml‐1)‐1). This result is in contrast with reported findings from humans in which insulin sensitivity is significantly reduced in the presence of hypertension.

Age‐related analysis of insulin resistance, body weight and arterial pressure in the Zucker fatty rat

The evolution with ageing of insulin resistance, body weight (BW) and mean arterial pressure (MAP) was studied in a group of Zucker fatty rats (ZFRs, n= 22), between 7 and 16 weeks of age, compared with an age‐matched control group of Zucker lean rats (ZLRs, n= 22). The minimal model of glucose kinetics was applied to estimate glucose effectiveness, SG, and insulin sensitivity, SI, from insulinaemia and glycaemia measured during a 70 min intravenous glucose tolerance test. No correlation was found between SG and age in both ZFR and ZLR groups. No significant changes in mean SG between the two groups indicated no alteration of glucose‐mediated glucose disposal. Estimates of SI from individual ZFRs were independent of age and, on average, showed 83% reduction (P < 0.001) compared with the ZLR group. Despite the lack of alteration of SI with age, the ZFR group showed an age‐related increase of MAP, which correlated with increasing BW (r = 0.71 and P < 0.001). These results support the hypothesis that in our ZFRs, as a suitable genetic model of obesity and hypertension, insulin resistance is fully established at the age of 7 weeks and remains practically unaltered until at least the sixteenth week. An age‐related increase in arterial pressure, observed in this strain, relates more properly to increasing BW, rather than insulin resistance. Development of hypertension with increasing age and BW may result from an enhanced insulin‐mediated activity of the sympathetic nervous system, as observed in our previously reported study.

Systemic Administration of Mesenchymal Stem Cells Increases Neuron Survival after Global Cerebral Ischemia In Vivo (2VO)

Although many studies have shown that administration of stem cells after focal cerebral ischemia improves brain damage, very little data are available concerning the damage induced by global cerebral ischemia. The latter causes neuronal death in selectively vulnerable areas, including the hippocampal CA1 region. We tested the hypothesis that intravenous infusion of bone marrowderived stromal cells (mesenchimal stem cells, MSC) reduce brain damage after transient global ischemia. In adult male Sprague-Dawley rats transient global ischemia was induced using bilateral common carotid artery occlusion for 20 min in addition to controlled hypotension. Five days after, the animals were anaesthetized with urethane and the brain was fixed, sectioned and stained with hematoxylin-eosin to investigate histological damage. MSC did not fully protect against ischemic damage, as the number of viable neurons in this group was lower than in normal (sham-operated) rats. However, in MSC-treated rats the number of viable CA1 pyramidal neurons was significally higher than in rats that had been subjected to ischemia but not treated with MSC. We conclude that intravenous administration of MSC after transient global ischemia reduces hippocampal damage.

Age-related analysis of glucose metabolism in spontaneously hypertensive and normotensive rats

This study was designed to investigate the effect of both hypertension and ageing on the efficiency of glucose metabolism. A 12‐sample, 120 min intravenous glucose tolerance test (IVGTT) was applied to 36 rats: two groups of nine young (12 weeks) spontaneously hypertensive and Wistar Kyoto rats (Y‐SHR and Y‐WKY group, respectively) and two groups of nine old (40 weeks) SHR and WKY rats (O‐SHR and O‐WKY group, respectively). Insulinaemia and glycaemia data were interpreted in terms of estimates of glucose effectiveness, SG, and insulin sensitivity, SI, provided by the minimal model of glucose kinetics. The possible link between insulin resistance and hypertension was investigated by comparing Y‐SHR vs. Y‐WKY and O‐SHR vs. O‐WKY groups. Comparison of O‐SHR vs. Y‐SHR and O‐WKY vs. Y‐WKY groups enabled us to investigate the role of age in the development of abnormalities in glucose metabolism. No significant differences (P > 0.05) were observed in the mean SG and SI estimates between SHR and age‐matched WKY groups. This finding indicates that exposure of SHR to high blood pressure levels does not necessarily lead to the development of insulin resistance and impaired glucose effectiveness. Similarly, no significant differences (P > 0.05) were observed in SG and SI estimates between old and young SHR and WKY groups. This finding indicates that, in this animal model of hypertension, insulin sensitivity and glucose effectiveness do not even deteriorate with ageing.

Actions of microelectrophoretically applied glucocorticoid hormones on reticular formation neurones in the rat

The effects of microelectrophoretic application of hydrocortisone (HC) and corticosterone (CS) on single neurones of the brainstem reticular formation (RF) were investigated in rats under urethane anaesthesia. Ejecting currents generally ranged from 5 to 20nA. HC and CS behaved similarly in that they produced an excitatory effect in 26% and 24% of the neurones, respectively, an inhibition in 15% and 17% and no effect in 59% of neurones. The excitatory effects predominated in the caudal portion of the FR and the inhibitory effects in the rostral RF. The different distribution of the effects may be related to functional differences between the two RF areas.

The direct effect of insulin on barosensitive neurones in the nucleus tractus solitarii of rats.

The present investigation was designed to determine the direct effect of insulin on the spontaneous discharge of barosensitive neurones in the nucleus tractus solitarii (NTS) of rats anaesthetized with urethane. Microinjection of 20 nl insulin (10 IU/ml) into NTS decreased the spontaneous discharge of 38 of the 52 units studied (73.1%), and this decrease was augmented by increasing the concentration to 40 IU/ml. Microinjections of insulin vehicle, glucose, hydralazine or phenylephr- ine did not elicit significant changes in the spontaneous discharge of NTS barosensitive neurones. These results demonstrate that insulin inhibits the spontaneous discharge of barosensitive NTS neurones. They suggest that insulin increases sympathetic nervous activity via a central neural mechanism and may play a role in the modulation of cardiovascular information within the NTS.

C-Peptide-based assessment of insulin secretion in the Zucker Fatty rat: a modelistic study.

A C-peptide-based assessment of β-cell function was performed here in the Zucker fatty rat, a suitable animal model of human metabolic syndrome. To this aim, a 90-min intravenous glucose tolerance test (IVGTT) was performed in seven Zucker fatty rats (ZFR), 7-to-9week-old, and seven age-matched Zucker lean rats (ZLR). The minimal model of C-peptide (CPMM), originally introduced for humans, was adapted to Zucker rats and then applied to interpret IVGTT data. For a comprehensive evaluation of glucose tolerance in ZFR, CPMM was applied in combination with the minimal model of glucose kinetics (GKMM). Our results showed that the present CPMM-based interpretation of data is able to: 1) provide a suitable fit of C-Peptide data; 2) achieve a satisfactory estimation of parameters of interest 3) quantify both insulin secretion by estimating the time course of pre-hepatic secretion rate, SR(t), and total insulin secretion, TIS, and pancreatic sensitivity by means of three specific indexes of β-cell responsiveness to glucose stimulus (first-phase, Ф1, second-phase, Ф2, and steady-state, Фss, never assessed in Zucker rats before; 4) detect the significant enhancement of insulin secretion in the ZFR, in face of a severe insulin-resistant state, previously observed only using a purely experimental approach. Thus, the methodology presented here represents a reliable tool to assess β-cell function in the Zucker rat, and opens new possibilities for the quantification of further processes involved in glucose homeostasis such as the hepatic insulin degradation.

Actions of 3α,5α-tetrahydrodeoxycorticosterone on single neurones of the mesencephalic reticular formation in the rat

Abstract The effects of microinjections of 3α,5α-tetrahydrodeoxycorticosterone (3α-THDOC) on single neurones of the mesencephalic reticular formation (MRF) were investigated in rats anaesthetized with urethan. Microinjections of approximately 100 nl of 0.5–2 μM 3α-THDOC inhibited firing of 105 of 112 neurones (94%). Microinjections of approximately 100 nl of 100–250 nM of 3α-THDOC did not alter neuronal activity, but in 52 of 68 cases (76%) it potentiated the inhibitory action of microiontophoretically applied γ-aminobutyric acid (GABA). The 3β-isomer of tetrahydrodeoxycorticosterone did not elicit any changes in neuronal firing. The effects of 3α-THDOC were reversibly antagonized by microiontophoretically applied bicuculline. This ‘in vivo’ study supports the hypothesis that 3α-THDOC may function as endogenous modulator of GABA A -mediated inhibition in various physiopathological conditions.