Remodeling of the number and structure of dendritic spines in the medial amygdala: From prepubertal sexual dimorphism to puberty and effect of sexual experience in male rats.

The posterodorsal medial amygdala (MePD) is a sexually dimorphic area and plays a central role in the social behavior network of rats. Dendritic spines modulate synaptic processing and plasticity. Here, we compared the number and structure of dendritic spines in the MePD of prepubertal males and females and postpubertal males with and without sexual experience. Spines were classified and measured after three-dimensional image reconstruction using DiI fluorescent labeling and confocal microscopy. Significantly differences are as follows: (a) Prepubertal males have more proximal spines, stubby/wide spines with long length and large head diameter and thin and mushroom spines with wide neck and head diameters than prepubertal females, whereas (b) prepubertal females have more mushroom spines with long neck length than age-matched males. (c) In males, the number of thin spines reduces after puberty and, compared to sexually experienced counterparts, (d) naive males have short stubby/wide spines as well as mushroom spines with reduced neck diameter. In addition, (e) sexually experienced males have an increase in the number of mushroom spines, the length of stubby/wide spines, the head diameter of thin and stubby/wide spines and the neck diameter of thin and mushroom spines. These data indicate that a sexual dimorphism in the MePD dendritic spines is evident before adulthood and a spine-specific remodeling of number and shape can be brought about by both puberty and sexual experience. These fine-tuned ontogenetic, hormonally and experience-dependent changes in the MePD are relevant for plastic synaptic processing and the reproductive behavior of adult rats.

Low-level laser therapy improves the inflammatory profile of rats with heart failure.

Following heart failure (HF), immune activation leads to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Low-level laser therapy (LLLT) has been used as an anti-inflammatory treatment in several disease conditions. However, the effect of LLLT on the skeletal muscle of rats with HF remains unclear. The present report aimed to evaluate the influence of LLLT on the inflammatory profile of rats with HF. The left coronary artery was ligated to induce HF and a sham operation was performed in the control groups. Male Wistar rats (n=49) were assigned to one of six groups: placebo sham rats (P-Sham; n=8), LLLT at a dose of 3 J/cm(2) sham rats (3 J/cm(2)-Sham; n=8), LLLT at a dose of 21 J/cm(2) sham rats (21 J/cm(2)-Sham; n=8), placebo HF rats (P-HF; n=9), LLLT at a dose of 3 J/cm(2) HF rats (3 J/cm(2)-HF; n=8), and LLLT at a dose of 21 J/cm(2) HF rats (21 J/cm(2)-HF; n=8). Four weeks after myocardial infarction or sham surgery, rats were subjected to LLLT (InGaAlP 660 nm, spot size 0.035 cm(2), output power 20 mW, power density 0.571 W/cm(2), energy density 3 or 21 J/cm(2), exposure time 5.25 s and 36.75 s) on the right gastrocnemius for 10 consecutive days. LLLT reduced plasma IL-6 levels (61.3 %; P<0.01), TNF-α/IL-10 (61.0 %; P<0.01) and IL-6/IL-10 ratios (77.3 %; P<0.001) and increased IL-10 levels (103 %; P<0.05) in the 21 J/cm(2)-HF group. Moreover, LLLT reduced the TNF-α (20.1 % and 21.3 %; both P<0.05) and IL-6 levels (54.3 % and 37.8 %; P<0.01 and P<0.05, respectively) and the IL-6/IL-10 ratio (59.7 % and 42.2 %; P<0.001 and P<0.05, respectively) and increased IL-10 levels (81.0 % and 85.1 %; both P<0.05) and the IL-10/TNF-α ratio (171.5 % and 119.8 %; P<0.001 and P<0.05, respectively) in the gastrocnemius in the 3 J/cm(2)-HF and 21 J/cm(2)-HF groups. LLLT showed systemic and skeletal muscle anti-inflammatory effects in rats with HF.

Selective brain neuronal and glial losses without changes in GFAP immunoreactivity: Young versus mature adult Wistar rats.

Normal ageing results in brain selective neuronal and glial losses. In the present study we analyze neuronal and glial changes in Wistar rats at two different ages, 45 days (young) and 420 days (mature adult), using Nissl staining and glial fibrillary acidic protein (GFAP) immunohistochemistry associated to the Sholl analysis. Comparing mature adults with young rats we noted the former present a decrease in neuronal density in the cerebral cortex, corpus callosum, pyriform cortex, L.D.D.M., L.D.V.L., central medial thalamic nucleus and zona incerta. A decrease in glial density was found in the dorsomedial and ventromedial hypothalamic nuclei. Additionally, the neuron/glia ratio was reduced in the central medial thalamic nucleus and increased in the habenula. No changes were found in the neuronal and glial densities or neuron/glia ratio in the other studied regions. The number of astrocytic primary processes and the number of intersections counted in the Sholl analysis presented no significant difference in any of the studied regions. Overall, neither GFAP positive astrocytic density nor GFAP immunoreactivity showed alteration.

Involvement of the Cholinergic Parameters and Glial Cells in Learning Delay Induced by Glutaric Acid: Protection by N-Acetylcysteine.

Dysfunction of basal ganglia neurons is a characteristic of glutaric acidemia type I (GA-I), an autosomal recessive inherited neurometabolic disease characterized by deficiency of glutaryl-CoA dehydrogenase (GCDH) and accumulation of glutaric acid (GA). The affected patients present clinical manifestations such as motor dysfunction and memory impairment followed by extensive striatal neurodegeneration. Knowing that there is relevant striatal dysfunction in GA-I, the purpose of the present study was to verify the performance of young rats chronically injected with GA in working and procedural memory test, and whether N-acetylcysteine (NAC) would protect against impairment induced by GA. Rat pups were injected with GA (5 µmol g body weight-1, subcutaneously; twice per day; from the 5th to the 28th day of life) and were supplemented with NAC (150 mg/kg/day; intragastric gavage; for the same period). We found that GA injection caused delay procedural learning; increase of cytokine concentration, oxidative markers, and caspase levels; decrease of antioxidant defenses; and alteration of acetylcholinesterase (AChE) activity. Interestingly, we found an increase in glial cell immunoreactivity and decrease in the immunoreactivity of nuclear factor-erythroid 2-related factor 2 (Nrf2), nicotinic acetylcholine receptor subunit alpha 7 (α7nAChR), and neuronal nuclei (NeuN) in the striatum. Indeed, NAC administration improved the cognitive performance, ROS production, neuroinflammation, and caspase activation induced by GA. NAC did not prevent neuronal death, however protected against alterations induced by GA on Iba-1 and GFAP immunoreactivities and AChE activity. Then, this study suggests possible therapeutic strategies that could help in GA-I treatment and the importance of the striatum in the learning tasks.

Endurance and resistance exercise training programs elicit specific effects on sciatic nerve regeneration after experimental traumatic lesion in rats.

OBJECTIVE: To evaluate the effects of endurance, resistance, and a combination of both types of exercise training on hindlimb motor function recovery and nerve regeneration after experimental sciatic nerve lesion in rats. METHODS: Sciatic nerve crush was performed on adult male rats, and after 2 weeks of the nerve lesion, the animals were submitted to endurance, resistance, and a combination of endurance-resistance training programs for 5 weeks. Over the training period, functional recovery was monitored weekly using the Sciatic Functional Index (SFI) and histological and morphometric nerve analyses were used to assess the nerve regeneration at the end of the trainings. RESULTS: The SFI values of the endurance-trained group reached the control values from the first posttraining week and were significantly better than both the resistance-trained group at the first, second, and third posttraining weeks and the concurrent training group at the first posttraining week. At the distal portion of the regenerating sciatic nerve, the endurance-trained group showed a greater degree of the myelinated fiber maturation than the sedentary, resistance-trained, and concurrent training groups. Furthermore, the endurance-trained group showed a smaller percentage area of endoneurial connective tissue and a greater percentage area of myelinated fibers than the sedentary group. CONCLUSION: These data provide evidence that endurance training improves sciatic nerve regeneration after an experimental traumatic injury and that resistance training or the combination of 2 strategies may delay functional recovery and do not alter sciatic nerve fiber regeneration.

Neuronal somatic volume of posteroventral medial amygdala cells from males and across the estrous cycle of female rats.

The posteroventral medial amygdala (MePV) is a brain area where gonadal hormones have neurotrophic effects in rats. The aim of the present study was to estimate the MePV neuronal somatic volume from males and diestrus, proestrus and estrus female Wistar rats (n=5 in each group) in an attempt to identify a possible sexual dimorphism in this parameter. The effect of laterality was also evaluated. The brains of adult animals were sectioned (1 microm), stained with 1% toluidine blue and serial-section reconstructions of each neuronal cell body were obtained. Images from both left and right MePV were studied and the somatic volume was estimated using the Cavalieri method in combination with the point counting technique. Results were compared according to sex and phase of the estrous cycle using a two-way ANOVA for repeated measures followed by the least significance difference test. Mean neuronal somatic volume showed a statistical difference among groups and the post hoc comparisons revealed that males present higher values than females in proestrus and estrus (p<0.05). On the other hand, neither a laterality effect (p=0.6) nor an interaction between groups and laterality (p=0.4) were found. Our results indicate that cell body volume in the MePV is distinct when comparing males to females in the different phases of the estrous cycle. Through dynamic changes modulated by sex steroids, it is likely that this morphological plasticity within the MePV may be affecting the functioning of local neurons and their integrated roles in neural circuits relevant for neuroendocrine control and reproductive behaviors.

Early handling, but not maternal separation, decreases emotional responses in two paradigms of fear without changes in mesolimbic dopamine.

This study aimed at identifying the effects of neonatal handling (H) and maternal separation (MS) on two paradigms of fear, learned and innate, and on the tyrosine hydroxylase (TH) immunoreactive cells in adult life. Wistar rats were daily handled with a brief maternal separation, maternal separated for 3 h or left undisturbed during the first 10 days of life. Behavioural responses in the open-field (innate fear) and conditioned fear (learned fear) were evaluated. Moreover, a semi-quantitative analysis of TH immunoreactivity in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNpc) was performed using optical densitometry and confirmed by planar measurements of neuronal density. Early handling decreased behaviour responses of innate and learned fear in adult life, while maternal separation had no significant long-lasting effect on these responses compared to the non-handled group. The behavioural effects of early handling could not be explained by changes in the density of midbrain dopaminergic cells, which were not affected by handling or maternal separation.

Gonadal hormone regulation of glial fibrillary acidic protein immunoreactivity in the medial amygdala subnuclei across the estrous cycle and in castrated and treated female rats.

The medial amygdala (MeA) is a sexually dimorphic area that modulates neuroendocrine and behavioral activities and where gonadal hormones play an important role in neuron-glial and synaptic plasticity. Immunohistochemistry was used to identify the astrocytic marker glial fibrillary acidic protein (GFAP) in the different MeA subnuclei--anterodorsal (MeAD), posterodorsal (MePD) and posteroventral (MePV)--of intact female rats in the different phases of the estrous cycle and in ovariectomized females treated with hormonal substitutive therapy. Data semi-quantified by optical densitometry showed that, in the proestrus phase, the GFAP immunoreactivity (GFAP-ir) was higher when compared to the other phases of the estrous cycle (P < 0.02). GFAP-ir was also higher in the MePD than in the MeAD or in the MePV (P < 0. 02). In ovariectomized females, injections of estradiol alone or estradiol plus progesterone increased GFAP-ir in the MePD and in the MePV (P < 0.001), but not in the MeAD (P > 0.3), when compared to control data. These findings suggest that astrocytic GFAP in the MeA subnuclei can be affected either by physiological levels or by hormonal manipulation of the ovarian steroids, which may contribute to the plasticity of local and integrated functional activities of these brain areas in female rats.

Influence of sex and estrous cycle, but not laterality, on the neuronal somatic volume of the posterodorsal medial amygdala of rats.

The aim of the present study was to measure the cell body volume of neurons from the posterodorsal subnucleus of the medial amygdala (MePD) of adult male (n=5) and diestrus, proestrus and estrus female (n=4-5 in each group) rats to reveal a possible sexual dimorphism, estrous cycle variations and laterality in this morphological parameter. The brains of adult Wistar rats were sectioned (1 microm), stained with 1% toluidine blue and the stereological estimation of neuronal soma volume of both sides of MePD was realized using the Cavalieri method and the technique of point counting. Data were compared by a two-way ANOVA for repeated measures and the least significance difference post hoc test. In the MePD, mean neuronal somatic volume showed a statistical difference among groups (p=0.005), but neither an effect of laterality (p=0.33) nor interactions between groups and laterality (p=0.78) were found. Post hoc test showed that males (mean+/-S.E.M., 2075.67+/-135.79 microm(3)) have larger mean neuronal somatic volume compared to females in proestrus (1503.30+/-44.46 microm(3)) and in estrus (1616.69+/-71.49 microm(3), p<0.05 in both cases), but not in diestrus (1940.78+/-129.68 microm(3), p>0.05). Moreover, diestrus females displayed larger mean neuronal somatic volume than proestrus female rats (p<0.05). It is suggested that neuronal somatic volume is another sexually dimorphic finding in the MePD, for which it is relevant to set apart the different phases of the estrous cycle to reveal the presence of gonadal hormones effects in the rat MePD neurons.

Glial fibrillary acidic protein immunodetection and immunoreactivity in the anterior and posterior medial amygdala of male and female rats.

The medial amygdala (MeA) has receptors for gonadal hormones and modulates reproductive behaviors in rats. Adult male and female rats were used for the immunodetection, a less accurate technique, and the immunohistochemistry for the astrocytic marker glial fibrillary acidic protein (GFAP) in the anterior and posterior MeA. Both procedures were done using polyclonal anti-GFAP and were quantified by densitometry. The first technique provided no evidence for a difference between sexes in the immunocontent of GFAP in any region of the MeA (p > 0.1). Nevertheless, the measure of the intensity of GFAP immunoreactivity (GFAP-IR) showed that females had a higher GFAP-IR in the posterodorsal (p < 0.01) and in the posteroventral subregions of the MeA (p < 0.01) than males. No sex difference was found in its anterodorsal part (p > 0.1). The present results point out the differences between these two above-mentioned techniques but add a new finding to the previously described sexual dimorphism in the MeA, i.e., the GFAP-IR. Data also suggest that probably astrocytes can be affected by sex steroids in this brain area. It is likely that this regionally specific difference in the GFAP-IR may contribute to the distinct functional roles that the MeA subregions have in male and female rats.

Sciatic nerve transection decrease substance P immunoreactivity in the lumbosacral spinal cord of the frog (Rana catesbeiana).

Using immunohistochemistry and optical densitometry, substance P (SP) was investigated in the lumbar spinal cord of the frog Rana catesbeiana after sciatic nerve transection. In control animals, there was a high density of SP fibers in the Lissauer's tract and in the mediolateral band of the dorsal gray matter. Other SP immunoreactive fibers were observed in the dorsal part of the lateral funiculus and in the ventral horn. No SP label was found in any cell bodies. After axotomy, SP immunoreactive fibers decreased in the Lissauer's tract on the same side of the lesion. The other regions remained labeled. The changes were observed at 3 days following axonal injury and persisted at 5, 8 and 15 days. At 20 days, there was no significant difference between the axotomized side and the control one, thus indicating a recovery of the SP expression. These results indicate that the frog may be used as a model to study the effects of peripheral axotomy, contributing to elucidate the SP actions in the pain neuropath.

Somatostatin-, calcitonin gene-related peptide, and gamma-aminobutyric acid-like immunoreactivitity in the frog lumbosacral spinal cord: distribution and effects of sciatic nerve transection.

Using immunohistochemistry and optical densitometry, somatostatin (SOM), calcitonin gene-related peptide (CGRP), and gamma-aminobutyric acid (GABA) were investigated in the lumbosacral spinal cord of the frog Rana catesbeiana after sciatic nerve transection. In control animals, the densest network of the SOM-, CGRP- and GABA-like immunoreactive fibers was located in the dorsal part of the lateral funiculus. SOM and GABA-like fibers were found in the dorsal terminal field and in the mediolateral band. The latter region showed CGRP and SOM-like immunoreactive cell bodies. SOM- and GABA-like immunoreactive neurons also occurred around the cavity of the central canal, and other GABA-like fibers were found in the ventral terminal field. While the ventral horn showed scarce somatostatin-like fibers, the putative motoneurons were immunoreactive for the two peptides investigated and GABA, but only a few SOM- and GABA-like fibers occurred in the ventral funiculus. After axotomy, GABA-like immunoreactivity decreased in the dorsal part of the lateral funiculus on the same side of the lesion. The other regions remained labeled. These changes were observed at 3 days following axonal injury and persisted at 5, 8 and 15 days. There was no significant difference in the pattern of CGRP- and SOM- immunoreactivity between the axotomized and the control sides. These results are discussed in relation to the effects of the peripheral axotomy on GABA, SOM, and CGRP expression in vertebrates, emphasizing the use of frogs as a model to study the effects of peripheral nerve injury.

Effect of prior exercise training and myocardial infarction-induced heart failure on the neuronal and glial densities and the GFAP-immunoreactivity in the posterodorsal medial amygdala of rats.

Exercise training has neuroprotective effects whereas myocardial infarction (MI) and heart failure (HF) can cause neuronal death and reactive gliosis in the whole amygdala. The posterodorsal medial amygdala (MePD) is involved with cardiovascular reflexes and the central control of sympathetic/parasympathetic responses. Our aim was to study the effects of prior exercise training and of MI-induced HF on the neuronal and glial densities and the glial fibrillary acidic protein-immunoreactivity (GFAP-ir) in the MePD of adult male rats. Animals (n= 5/group) were: control, sedentary submitted to a sham MI (Sed Sham), sedentary submitted to MI/HF (Sed HF), trained on a treadmill and submitted to a sham MI (T Sham) or trained on a treadmill and submitted to MI/HF (T HF). The number of neurons and glial cells in the MePD was estimated using the optical fractionator and the GFAP-ir was quantified by optical densitometry. In the respective groups, treadmill training improved physical performance and MI damaged near 40% of the left ventricle. There was a hemispheric lateralization effect on the density of neurons (higher in the right MePD), but no significant difference in either the neuronal or the glial densities due to experimental condition. Regional GFAP-ir results revealed that the Sed HF group had a higher expression in the left MePD compared to the control and the Sed Sham rats (p⟨0.01). The present data did not evidence the effects of training or MI/HF in the MePD cellular density, but indicate a possible local restructuring of astrocytic cytoskeleton after MI/HF in rats.

Cellular components of the human medial amygdaloid nucleus.

The medial nucleus (Me) is a superficial component of the amygdaloid complex. Here we assessed the density and morphology of the neurons and glial cells, the glial fibrillary acidic protein (GFAP) immunoreactivity, and the ultrastructure of the synaptic sites in the human Me. The optical fractionator method was applied. The Me presented an estimated mean neuronal density of 1.53 × 105 neurons/mm³ (greater in the left hemisphere), more glia (72% of all cells) than neurons, and a nonneuronal:neuronal ratio of 2.7. Golgi-impregnated neurons had round or ovoid, fusiform, angular, and polygonal cell bodies (10-30 µm in diameter). The length of the dendrites varied, and pleomorphic spines were found in sparsely spiny or densely spiny cells (1.5-5.2 spines/dendritic µm). The axons in the Me neuropil were fine or coarsely beaded, and fibers showed simple or notably complex collateral terminations. The protoplasmic astrocytes were either isolated or formed small clusters and showed GFAP-immunoreactive cell bodies and multiple branches. Furthermore, we identified both asymmetrical (with various small, clear, round, electron-lucent vesicles and, occasionally, large, dense-core vesicles) and symmetrical (with small, flattened vesicles) axodendritic contacts, also including multisynaptic spines. The astrocytes surround and may compose tripartite or tetrapartite synapses, the latter including the extracellular matrix between the pre- and the postsynaptic elements. Interestingly, the terminal axons exhibited a glomerular-like structure with various asymmetrical contacts. These new morphological data on the cellular population and synaptic complexity of the human Me can contribute to our knowledge of its role in health and pathological conditions.

N-acetylcysteine prevents spatial memory impairment induced by chronic early postnatal glutaric acid and lipopolysaccharide in rat pups.

BACKGROUND AND AIMS: Glutaric aciduria type I (GA-I) is characterized by accumulation of glutaric acid (GA) and neurological symptoms, such as cognitive impairment. Although this disease is related to oxidative stress and inflammation, it is not known whether these processes facilitate the memory impairment. Our objective was to investigate the performance of rat pups chronically injected with GA and lipopolysaccharide (LPS) in spatial memory test, antioxidant defenses, cytokines levels, Na+, K+-ATPase activity, and hippocampal volume. We also evaluated the effect of N-acetylcysteine (NAC) on theses markers. METHODS: Rat pups were injected with GA (5 umol g of body weight-1, subcutaneously; twice per day; from 5th to 28th day of life), and were supplemented with NAC (150 mg/kg/day; intragastric gavage; for the same period). LPS (2 mg/kg; E.coli 055 B5) or vehicle (saline 0.9%) was injected intraperitoneally, once per day, from 25th to 28th day of life. Oxidative stress and inflammatory biomarkers as well as hippocampal volume were assessed. RESULTS: GA caused spatial learning deficit in the Barnes maze and LPS potentiated this effect. GA and LPS increased TNF-α and IL-1ß levels. The co-administration of these compounds potentiated the increase of IL-1ß levels but not TNF-α levels in the hippocampus. GA and LPS increased TBARS (thiobarbituric acid-reactive substance) content, reduced antioxidant defenses and inhibited Na+, K+-ATPase activity. GA and LPS co-administration did not have additive effect on oxidative stress markers and Na+, K+ pump. The hippocampal volume did not change after GA or LPS administration. NAC protected against impairment of spatial learning and increase of cytokines levels. NAC Also protected against inhibition of Na+,K+-ATPase activity and oxidative markers. CONCLUSIONS: These results suggest that inflammatory and oxidative markers may underlie at least in part of the neuropathology of GA-I in this model. Thus, NAC could represent a possible adjuvant therapy in treatment of children with GA-I.

Morphofunctional analysis of sciatic nerve and motor performance of rats after cryotherapy with liquid nitrogen.

OBJECTIVE: This work evaluated sciatic nerve regeneration after cryotherapy. STUDY DESIGN: Rats underwent surgical access of the sciatic nerve and subsequent cryotherapy, crush lesion, or no manipulation. Walking-track, electroneuromyographic, and histomorphometric analyses were performed at 15, 30, and 70 postoperative days. RESULTS: At 15 days, the crush and cryotherapy groups showed significant morphofunctional impairment. At 30 days, functional loss was significant in the walking-track, but at 70 days, there were no significant differences between the groups. Amplitude was near zero for the crush group at 15 and 30 days and zero for the cryotherapy group. Measurement of latency was not possible in the latter group. Crush and cryotherapy groups showed greater amounts of myelinated fibers (by 30 days), with axonal diameter and width of the myelin sheath being less than in control group. CONCLUSIONS: Sciatic nerve lesion by application of liquid nitrogen is classified as axonotmesis, which is reversible.

Exercise alleviates hypoalgesia and increases the level of calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats.

OBJECTIVE: The aim of this study was to evaluate the effects of treadmill training on nociceptive sensitivity and immunoreactivity to calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats. METHODS: Male Wistar rats were divided into three groups: control, diabetic and trained diabetic. Treadmill training was performed for 8 weeks. The blood glucose concentrations and body weight were evaluated 48 h after diabetes induction and every 30 days thereafter. The nociceptive sensitivity was evaluated using the tail-flick apparatus. The animals were then transcardially perfused, and the spinal cords were post-fixed, cryoprotected and sectioned in a cryostat. Immunohistochemistry for calcitonin gene-related peptide analysis was performed on the dorsal horn of the spinal cord. RESULTS: The nociceptive sensitivity analysis revealed that, compared with the control and trained diabetic animals, the latency to tail deflection on the apparatus was longer for the diabetic animals. Optical densitometry demonstrated decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord in diabetic animals, which was reversed by treadmill training. CONCLUSION: We concluded that treadmill training can alleviate nociceptive hypoalgesia and reverse decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord of diabetic animals without pharmacological treatment.

Respiratory muscle training improves hemodynamics, autonomic function, baroreceptor sensitivity, and respiratory mechanics in rats with heart failure.

Respiratory muscle training (RMT) improves functional capacity in chronic heart-failure (HF) patients, but the basis for this improvement remains unclear. We evaluate the effects of RMT on the hemodynamic and autonomic function, arterial baroreflex sensitivity (BRS), and respiratory mechanics in rats with HF. Rats were assigned to one of four groups: sedentary sham (n = 8), trained sham (n = 8), sedentary HF (n = 8), or trained HF (n = 8). Trained animals underwent a RMT protocol (30 min/day, 5 day/wk, 6 wk of breathing through a resistor), whereas sedentary animals did not. In HF rats, RMT had significant effects on several parameters. It reduced left ventricular (LV) end-diastolic pressure (P < 0.01), increased LV systolic pressure (P < 0.01), and reduced right ventricular hypertrophy (P < 0.01) and pulmonary (P < 0.001) and hepatic (P < 0.001) congestion. It also decreased resting heart rate (HR; P < 0.05), indicating a decrease in the sympathetic and an increase in the vagal modulation of HR. There was also an increase in baroreflex gain (P < 0.05). The respiratory system resistance was reduced (P < 0.001), which was associated with the reduction in tissue resistance after RMT (P < 0.01). The respiratory system and tissue elastance (Est) were also reduced by RMT (P < 0.01 and P < 0.05, respectively). Additionally, the quasistatic Est was reduced after RMT (P < 0.01). These findings show that a 6-wk RMT protocol in HF rats promotes an improvement in hemodynamic function, sympathetic and vagal heart modulation, arterial BRS, and respiratory mechanics, all of which are benefits associated with improvements in cardiopulmonary interaction.

Treadmill training improves motor skills and increases tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta in diabetic rats.

The aim of this study was to evaluate the effects of treadmill training on motor skills and immunoreactivity to tyrosine hydroxylase in the substantia nigra pars compacta and ventral tegmental area from diabetic rats induced by streptozotocin. Male Wistar rats were divided into three groups: control, diabetic and trained diabetic. Treadmill training was performed for 8weeks. Blood glucose concentrations and body weight were evaluated 48h after diabetes induction and every 30days thereafter. Motor skills were evaluated on the rotarod and open field tests. Then, animals were transcardially perfused and the brains were post-fixed, cryoprotected and sectioned in a cryostat. Immunohistochemistry for tyrosine hydroxylase analyses was done in the ventral tegmental area and in the substantia nigra. Motor skills showed that diabetic animals had a decrease in the latency to fall and enhanced number of falls in the rotarod test compared to control and trained diabetic animals. In the open field, diabetic animals had a decrease in the number of crossed squares, rearings and spent a less time moving compared to control and trained diabetic animals. In diabetic animals, optical densitometry of immunohistochemistry showed that tyrosine hydroxylase reaction decreased in the ventral tegmental area and in the neurons and process in the substantia nigra. In the later region, that decrease was reversed by treadmill training. In conclusion, we demonstrated that treadmill training can reverse the loss of the motor skills, which was correlated to tyrosine hydroxylase immunoreactivity in the substantia nigra of diabetic animals without pharmacological treatment.

Thermographic evaluation of hind paw skin temperature and functional recovery of locomotion after sciatic nerve crush in rats.

INTRODUCTION: Peripheral nerves are often damaged by direct mechanical injury, diseases, and tumors. The peripheral nerve injuries that result from these conditions can lead to a partial or complete loss of motor, sensory, and autonomic functions, which in turn are related to changes in skin temperature, in the involved segments of the body. The aim of this study was to evaluate the changes in hind paw skin temperature after sciatic nerve crush in rats in an attempt to determine whether changes in skin temperature correlate with the functional recovery of locomotion. METHODS: Wistar rats were divided into three groups: control (n = 7), sham (n = 25), and crush (n = 25). All groups were subjected to thermographic, functional, and histological assessments. RESULTS: ΔT in the crush group was different from the control and sham groups at the 1st, 3rd and 7rd postoperative days (p<0.05). The functional recovery from the crush group returned to normal values between the 3rd and 4th week post-injury, and morphological analysis of the nerve revealed incomplete regeneration at the 4th week after injury. DISCUSSION: This study is the first demonstration that sciatic nerve crush in rats induces an increase in hind paw skin temperature and that skin temperature changes do not correlate closely with functional recovery.