Carla Christina Medalha

Effects of chronic treatment with corticosterone and imipramine on fos immunoreactivity and adult hippocampal neurogenesis.

In a previous study we showed that rats chronically treated with corticosterone (CORT) display anxiogenic behavior, evidenced by facilitation of avoidance responses in the elevated T-maze (ETM) model of anxiety. Treatment with the tricyclic antidepressant imipramine significantly reversed the anxiogenic effects of CORT, while inhibiting ETM escape, a response related to panic disorder. To better understand the neurobiological mechanisms underlying these behavioral effects, analysis of c-fos protein immunoreactivity (fos-ir) was used here to map areas activated by chronic CORT (200 mg pellets, 21-day release) and imipramine (15 mg/kg, IP) administration. We also evaluated the number of cells expressing the neurogenesis marker doublecortin (DCX) in the hippocampus and measured plasma CORT levels on the 21st day of treatment. Results showed that CORT increased fos-ir in the ventrolateral septum, medial amygdala and paraventricular hypothalamic nucleus and decreased fos-ir in the lateral periaqueductal gray. Imipramine, on the other hand, increased fos-ir in the medial amygdala and decreased fos-ir in the anterior hypothalamus. CORT also decreased the number of DCX-positive cells in the ventral and dorsal hippocampus, an effect antagonized by imipramine. CORT levels were significantly higher after treatment. These data suggest that the behavioral effects of CORT and imipramine are mediated through specific, at times overlapping, neuronal circuits, which might be of relevance to a better understanding of the physiopathology of generalized anxiety and panic disorder.

Aerobic exercise training and low-level laser therapy modulate inflammatory response and degenerative process in an experimental model of knee osteoarthritis in rats

OBJECTIVE The aim of this study was to evaluate the effects of an aerobic exercise training and low-level laser therapy (LLLT) (associated or not) on degenerative modifications and inflammatory mediators on the articular cartilage using an experimental model of knee OA. MATERIAL AND METHODS Fifty male Wistar rats were randomly divided into five groups: control group (CG); knee OA control group (OAC); OA plus exercise training group (OAT); OA plus LLLT group (OAL); OA plus exercise training associated with LLLT group (OATL). The exercise training (treadmill; 16 m/min; 50 min/day) and the laser irradiation (two points-medial and lateral side of the left joint; 24 sessions) started 4 weeks after the surgery, 3 days/week for 8 weeks. RESULTS The results showed that all treated groups showed (irradiated or not) a better pattern of tissue organization, with less fibrillation and irregularities along the articular surface and chondrocytes organization, a lower degenerative process measured by OARSI score and higher thickness values. Additionally, all treated group showed a reduced expression in IL-1β, caspase-3 and MMP-13 compared to OAC. Moreover, a lower caspase-3 expression was observed in OATL compared to OAL and OAT. CONCLUSION These results suggest that exercise training and LLLT were effective in preventing cartilage degeneration and modulating inflammatory process induced by knee OA.

Comparison of the effects of electrical field stimulation and low-level laser therapy on bone loss in spinal cord-injured rats.

OBJECTIVE This study investigated the effects of low-level laser therapy (LLLT) and electrical stimulation (ES) on bone loss in spinal cord-injured rats. MATERIALS AND METHODS Thirty-seven male Wistar rats were divided into four groups: standard control group (CG); spinal cord-injured control (SC); spinal cord-injured treated with laser (SCL; GaAlAs, 830 nm, CW, 30 mW/cm, 250 J/cm(2)); and spinal cord-injured treated with electrical field stimulation (SCE; 1.5 MHz, 1:4 duty cycles, 30 mW, 20 min). Biomechanical, densitometric, and morphometric analyses were performed. RESULTS SC rats showed a significant decrease in bone mass, biomechanical properties, and morphometric parameters (versus CG). SCE rats showed significantly higher values of inner diameter and internal and external areas of tibia diaphyses; and the SCL group showed a trend toward the same result (versus SC). No increase was found in either mechanical or densitometric parameters. CONCLUSION We conclude that the mentioned treatments were able to initiate a positive bone-tissue response, maybe through stimulation of osteoblasts, which was able to determine the observed morphometric modifications. However, the evoked tissue response could not determine either biomechanical or densitometric modifications.

Effects of chronic corticosterone and imipramine administration on panic and anxiety-related responses

It is known that chronic high levels of corticosterone (CORT) enhance aversive responses such as avoidance and contextual freezing. In contrast, chronic CORT does not alter defensive behavior induced by the exposure to a predator odor. Since different defense-related responses have been associated with specific anxiety disorders found in clinical settings, the observation that chronic CORT alters some defensive behaviors but not others might be relevant to the understanding of the neurobiology of anxiety. In the present study, we investigated the effects of chronic CORT administration (through surgical implantation of a 21-day release 200 mg pellet) on avoidance acquisition and escape expression by male Wistar rats (200 g in weight at the beginning of the experiments, N = 6-10/group) tested in the elevated T-maze (ETM). These defensive behaviors have been associated with generalized anxiety and panic disorder, respectively. Since the tricyclic antidepressant imipramine is successfully used to treat both conditions, the effects of combined treatment with chronic imipramine (15 mg, ip) and CORT were also investigated. Results showed that chronic CORT facilitated avoidance performance, an anxiogenic-like effect (P < 0.05), without changing escape responses. Imipramine significantly reversed the anxiogenic effect of CORT (P < 0.05), although the drug did not exhibit anxiolytic effects by itself. Confirming previous observations, imipramine inhibited escape responses, a panicolytic-like effect. Unlike chronic CORT, imipramine also decreased locomotor activity in an open field. These data suggest that chronic CORT specifically altered ETM avoidance, a fact that should be relevant to a better understanding of the physiopathology of generalized anxiety and panic disorder.

Chromosome damage and cytotoxicity in oral mucosa cells after 2 months of exposure to anabolic steroids (decadurabolin and winstrol) in weight lifting.

The aim of the present study was to evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis) in exfoliated buccal mucosa cells from anabolic steroid users after 2 months of exposure. Two experimental groups consisting of 15 adult males who practise weight lifting and are anabolic steroid users or 15 adult males who practise weight lifting, but are non-anabolic steroid users, were recruited. In addition, 20 sedentary males, who do not practise any physical activity regularly, were matched by age with experimental groups. No significant statistical differences (p>0.05) were noticed in individuals who practise physical activity only. On the other hand, an increase of micronucleated cells (MNCs) in anabolic steroid (decadurabulin and Winstrol) users was observed. Regarding cytotoxic parameters, the same observation has occurred, that is, significant statistical differences (p<0.05) were noticed in the group exposed to anabolic steroids when compared with other controls, as depicted by high frequencies of pyknosis, karyolysis and karyorrhexis. Taken together, our results suggest that genomic instability and cytotoxicity are induced by anabolic steroid administration in oral mucosa cells as assessed by the micronucleus test.

Low level laser therapy accelerates bone healing in spinal cord injured rats.

Bone loss occurs rapidly and consistently after the occurrence of a spinal cord injury (SCI), leading to a decrease in bone mineral density (BMD) and a higher risk of fractures. In this context, the stimulatory effects of low level laser therapy (LLLT) also known as photobiomodulation (PBM) have been highlighted, mainly due to its osteogenic potential. The aim of the present study was to evaluate the effects of LLLT on bone healing using an experimental model of tibial bone defect in SCI rats. Twenty-four female Wistar rats were randomly divided into 3 groups: Sham group (SG), SCI control group (SC) and SCI laser treated group (SL). Two weeks after the induction of the SCI, animals were submitted to surgery to induce a tibial bone defect. Treatment was performed 3days a week, for 2weeks, at a single point over the area of the injury, using an 808nm laser (30mW, 100J/cm(2); 0.028cm(2), 1.7W/cm², 2.8J). The results of the histological and morphometric evaluation demonstrated that the SL group showed a larger amount of newly formed bone compared to the SC group. Moreover, a significant immunoexpression of runt-related transcription factor 2 (RUNX2) was observed in the SL group. There was no statistical difference in the biomechanical evaluation. In conclusion, the results suggest that LLLT accelerated the process of bone repair in rats with complete SCI.

Involvement of the histaminergic system on appetitive learning and its interaction with haloperidol in goldfish

This study investigated the actions of the histaminergic system on appetitive learning and memory, and its interaction with the dopaminergic system in goldfish. It consisted of nine sessions, in which fish were tested in a four-arm tank. On day 1, the animals were habituated for 10 min. On day 2, they were placed in one arm and had to find food at the left or the right arm. Time to begin feeding was recorded, and the procedure repeated for more 3 days (training phase). On training day 4, seven groups were injected with saline, seven with haloperidol (2.0 mg/kg) and one with DMSO solution before training and after feeding, three groups received saline, six chlorpheniramine (CPA) (1.0, 4.0 and 8.0 mg/kg), and six l-histidine (LH) (25, 50 and 100 mg/kg). Saline groups were considered as control of CPA and LH treated groups and DMSO as control of haloperidol. A non-injected group was also included. Testing occurred after 24 h. A reversal procedure was conducted 24h after testing and repeated for 3 days. The groups receiving CPA at 1.0 and 8.0 mg/kg and LH at 25, 50 and 100 mg/kg differed between Test and Reversal day 1. Pre-treatment with haloperidol plus 8.0 mg/kg of CPA and 25 and 50 mg/kg of LH reverted the treatment effect. However, in the groups treated with 1.0 mg/kg of CPA and 100 mg/kg of LH, the difference remained. This study confirmed the interaction between the histaminergic and the dopaminergic systems on memory process in goldfish.

Dual role of cyclooxygenase-2 during tissue repair induced by low level laser therapy: An intriguing issue

Abstract Tissue repair is an excellent example of pathophysiological model for studying the role of cyclooxygenase-2 (COX-2) on eukaryotic cells. It has been established that two COX isoforms are expressed in human tissues: constitutive or induced. COX-1 activity is constitutive, present in nearly all cell types at a constant level; COX-2 activity is normally absent from cells, and when induced, the protein levels increase and decrease in a matter of hours after a single stimulus. Thus, the purpose of this review was to describe the role of COX-2 during tissue repair induced by low level laser therapy (LLLT) in humans and experimental models. COX-2 expression has been implicated in the onset or the exacerbation of inflammation during tissue repair induced by LLLT in a number of studies, Many studies are conducted to investigate the role of COX-2 during tissue repair induced by LLLT using different experimental protocols and dosages. Therefore, this is an area that warrants investigation, since the estimation of COX-2 expression from using such important techniques in therapeutics with respect to tissue repair will be added to those already established in the literature as a way to improve health status and prevention of side effects.

The effects of low level laser therapy on injured skeletal muscle

The main purpose of the present study was to investigate the effects of low-level laser therapy (LLLT) used in two different fluencies on injured skeletal muscle after cryolesion by means of histopathological analysis and immunohistochemistry for COX-2. A total of sixty male Wistar rats were randomly distributed into three groups: injured animals without any treatment; 808 nm laser treated group, at 10 J/cm² and 808 nm laser treated group, at 50 J/cm². Each group was divided into two different subgroups (n=10) on days 6 and 13 post-injury. The results showed that the animals irradiated with laser at 10 J/cm² or 50 J/cm² presented the areas with cell infiltrate and pointed out to minor and mild areas with destroyed zones compared with the control group. Also, a COX-2 downregulation was noticed in the groups exposed to laser at two fluences evaluated in this study. Significant statistically differences (p<0.05) were noticed to collagen deposition in the laser treated animals, with the fluence of 50 J/cm2 when compared to the other groups on day 13 post-surgery. Taken together, these results suggested that laser therapy could have positive effects on muscle repair in the rats after cryolesion.

Temporal modifications in bone following spinal cord injury in rats.

Introduction The aim of this study was to investigate the temporal modifications in bone mass, bone biomechanical properties and bone morphology in spinal cord injured rats 2, 4 and 6 weeks after a transection. Material and methods Control animals were randomly distributed into four groups (n = 10 each group): control group (CG) – control animals sacrificed immediately after surgery; spinal cord-injured 2 weeks (2W) – spinal cord-injured animals sacrificed 2 weeks after surgery; spinal cord-injured 4 weeks (4W) – spinal cord-injured animals sacrificed 4 weeks after surgery; spinal cord-injured 6 weeks (6W) – spinal cord-injured animals sacrificed 6 weeks after surgery. Results Biomechanical properties of the right tibia were determined by a three-point bending test and injured animals showed a statistically significant decrease in maximal load compared to control animals. The right femur was used for densitometric analysis and bone mineral content of the animals sacrificed 4 and 6 weeks after surgery was significantly higher compared to the control animals and animals sacrificed 2 weeks after surgery. Histopathological and morphological analysis of tibiae revealed intense resorptive areas in the group 2 weeks after injury only. Conclusions The results of this study show that this rat model is a valuable tool to investigate bone remodeling processes specifically associated with SCI. Taken together, our results suggest that spinal cord injury induced bone loss within 2 weeks after injury in rats.