Vladimir Ajdzanovic

Sensorimotor cortex ablation induces time-dependent response of ACTH cells in adult rats: Behavioral, immunohistomorphometric and hormonal study

Traumatic brain injury (TBI) represents a serious event with far reaching complications, including pituitary dysfunction. Pars distalis corticotropes (ACTH cells), that represent the active module of hypothalamo-pituitary-adrenocortical axis, seem to be affected as well. Since pituitary failure after TBI has been associated with neurobehavioral impairments the aim of this study was to evaluate the effects of TBI on recovery of motor functions, morphology and secretory activity of ACTH cells in the pituitary of adult rats. Wistar male rats, initially exposed to sensorimotor cortex ablation (SCA), were sacrificed at the 2nd, 7th, 14th and 30th days post-surgery (dps). A beam walking test was used to evaluate the recovery of motor functions. Pituitary glands and blood were collected for morphological and hormonal analyses. During the first two weeks post-injury increased recovery of locomotor function was detected, reaching almost the control value at day 30. SCA induces significant increase of pituitary weights compared to their time-matched controls. The volume of ACTH-immunopositive cells was reduced at the 7th dps, while at the 14th dps their volume was enlarged, in comparison to corresponding sham controls. Volume density of ACTH cells was increased only at 14th dps, while at day 30 this increase was insignificant. The plasma level of ACTH transiently increased after the injury. The most pronounced changes were observed at the 7th and 14th dps, and were followed by decrease toward control levels at the 30th dps. Thus, temporal changes in the hypothalamic-pituitary-adrenal axis after traumatic brain injury appear to correlate with the recovery process.

Cortical ablation induces time-dependent changes in rat pituitary somatotrophs and upregulates growth hormone receptor expression in the injured cortex.

The pituitary appears to be vulnerable to brain trauma, and its dysfunction is a common feature after traumatic brain injury. The role of pituitary growth hormone (GH) in brain repair after injury has been envisaged, but more studies must be performed to understand completely the importance of GH in these processes. Because some of the neuroprotective effects of GH are mediated directly through the GH receptor (GHR), we examined GHR expression in the rat cerebral cortex after sensorimotor cortex ablation. RT‐PCR, immunohistochemistry, and double immunofluorescence had been performed to analyze the correlation between GHR expression in the injured cortex and activity of GH cells in the pituitary. Our results showed that the volume of GH‐immunopositive cells was reduced at days 2 and 7 postsurgery (dps), and volume density of GH cells was significantly decreased at 14 dps, all compared with appropriate sham controls. At 30 dps all investigated parameters had returned to control level. In the injured cortex, GHR expression was transiently upregulated. Increased GHR immunoreactivity was observed in reactive astrocytes at 7 and particularly at 14 dps. In neuronal cells, an increase of GHR immunoreactivity was seen in neuronal cell bodies and well‐defined primary dendrites at 14 and especially at 30 dps. The results presented here suggest that, during recovery from brain injury, changes in activity of pituitary GH cells result in upregulation of GHR that may have a role in neuronal arborization and glial proliferation in the injured cortex.

Nandrolone decanoate and physical activity affect quadriceps in peripubertal rats

Anabolic androgenic steroids (AASs) are synthetic analogs of testosterone often used by athletes to increase the skeletal muscle mass. Our goal was to examine the effects of physical activity and physical activity combined with supraphysiological doses of nandrolone on functional morphology of the quadriceps muscle. The study included 32 peripubertal Wistar rats, divided into 4 groups: control (T-N-), nandrolone (T-N+), physical activity (T+N-) and physical activity plus nandrolone (T+N+) groups. The T+N- and T+N+ group swam for 4 weeks, 1 h/day, 5 days/week. The T-N+ and T+N+ groups received nandolone decanoate (20 mg/kg b.w.) once per week, subcutaneously. Subsequently, the rats were sacrificed and muscle specimens were prepared for the processing. Tissue sections were histochemically and immunohistochemically stained, while the image analysis was used for quantification. Longitudinal diameter of quadriceps muscle cells was increased for 21% in T-N+, for 57% in T+N- and for 64% in T+N+ group while cross section muscle cell area was increased in T-N+ for 19%, in T+N- for 47% and in T+N+ group for 59%, compared to the control. Collagen fibers covered area was increased in T-N+ group for 36%, in T+N- for 109% and in T+N+ group for 159%, compared to the control. Erythrocyte depots were decreased in T-N+ group and increased in T+N- and T+N+ group, in comparison with T-N-. VEGF depots were increased in all treated groups. Chronic administration of supraphysiological doses of AASs alone or in combination with physical activity induces hypertrophy and significant changes in the quadriceps muscle tissue structure.

Immunohistomorphometric Characteristics Of Pituitary GH Cells In Infant And Peripubertal Female Rats After Treatment With Estradiol Or Human Chorionic Gonadotropin

Abstract The effects of estradiol-dipropionate (EDP) or human chorionic gonadotropin (hCG) on immunohistomorphometric characteristics of pituitary GH cells in infant and peripubertal female rats were investigated. The first group of females received five injections of EDP (0.25 mg/kg b.w.) during the neonatal period of life, and was further divided into two subgroups which were sacrificed at the infantile period (17th day) or at the peripubertal period (38th day). The second group received two doses of hCG (50 IU/kg b.w.) on the 15th and 16th day of life in the first subgroup, and on the 36th and 37th days of life in the second subgroup, while they were sacrificed 24 h after the last treatment, respectively. The control females were injected with an equivalent volume of the vehicle and sacrificed according to the appropriate schedules as the hormone treated rats. EDP treatment decreased GH cell volume density in infant and peripubertal females, by 38% and 76% (p<0.05) respectively, in comparison with the controls. The number of GH cells per mm2 in infantile and peripubertal period was decreased in EDP treated animals by 26% and 53% (p<0.05) respectively, compared to the controls. Also, upon EDP treatment in both periods, GH cells were diminished in size and less intensely immunolabelled than in the control groups. The morphometric parameters in animals treated with hCG were insignificantly changed in both analyzed periods, in comparison with the controls. Unlike hCG, EDP manifested clear inhibitory effects on the immunohistomorphometric characteristics of GH cells in examined female rats.

Pituitary ACTH cells in female rats after neonatal treatment with SRIH-14.

The prolonged effects of neonatal SRIH-14 treatment on pituitary ACTH cells were investigated. Neonatal female rats were injected subcutaneously with SRIH (20 microg/100g b.w.) every 12 hours for five consecutive days (3rd-7th day of life). Groups of rats were then killed at the juvenile (16th day), peripubertal (38th day) or adult (80th day) stage. ACTH cells were visualized using the peroxidase-antiperoxidase immunocytochemical procedure. Morphometry and stereology were used to evaluate the ACTH-immunoreactive cell volume and volume density. The histological and immunocytochemical characteristics of ACTH cells in neonatally treated females were changed in all examined periods. Thus, SRIH-14 induced significant (p<0.05) decreases of ACTH cell volume in juvenile, peripubertal and adult rats by 26%, 39% and 14%, respectively, in comparison to the corresponding controls. The volume density of ACTH cells was also diminished (by 31%; p<0.05) at the juvenile stage in comparison with the corresponding controls. In peripubertal and adult rats, the volume densities of ACTH cells were somewhat lower (17% and 14%, respectively), but the decreases did not reach statistical significance. These findings suggest that neonatal treatment with SRIH-14 exerts a marked prolonged inhibitory effect on ACTH cell morphology extending to the adult period of life.