Administration of diets with a high lead content to rodents during suckling causes growth impairment, hematological alter- ations, breakdown of the blood-brain bar- rier, and higher pup mortality (14,15). More- over, significant effects on neuromotor de- velopment of rats have also been described. Reiter and colleagues (16) reported delay in development of righting reflex and eye open- ing in animals exposed to lead acetate in the drinking water through gestation and lacta- tion. These data were confirmed by Luthman and colleagues (17), who described delayed eye opening and impairment in negative geo- taxis test performance during postnatal ip lead acetate treatment. Grant and colleagues (18) reported significant delays in vaginal opening in female pups and in the develop- ment of surface- and free-fall-righting re- flexes. Similarly, Livesey and colleagues (19) reported that animals exposed to lead from birth to 20 days of age presented retardation in the development of free-fall righting and acoustic startle reflexes. However, a statisti- cally significant effect of lead treatment on body weight was evidenced in these studies. Since it is well known that undernutrition is causally related to neurobehavioral develop- ment retardation (20), it becomes difficult to attribute these deficits solely to lead exposure. Studies using milder forms of lead in- toxication have revealed no differences in weight gain, but significant effects on adult rat behavior (21,22), confirming the view of a deleterious role for lead. However, develop- mental studies without concomitant undernu- trition are still lacking in the literature. There- fore, in the present study we investigated the effects of chronic lead exposure, starting at a prenatal age, on the neurobehavioral develop- ment of rats using a protocol of lead intoxica- tion that does not affect weight gain (21).
This study investigates the effect of the overexpression of the placental growth factor (PGF) and hyperoxia on lung development and determines whether anti-PGF antibody ameliorates hyperoxia-mediated impairment of lung development in newborn rats. After exposure to normoxic conditions for seven days, newborn rats subjected to normoxia were intraperitoneally or intratracheally injected with physiological saline, adenovirus-negative control (Ad-NC), or adenovirus-PGF (Ad-PGF) to create the Normoxia, Normoxia +Ad-NC, and Normoxia+Ad-PGF groups, respectively. Newborn rats subjected to hyperoxia were intraperitoneally injected with physiological saline or anti-PGF antibodies to create the Hyperoxia and Hyperoxia +anti-PGF groups, respectively. Our results revealed signi ﬁcant augmentation in the levels of PGF and its receptor Flt-1 in the lung tissues of newborn rats belonging to the Normoxia +Ad-PGF or Hyperoxia groups. PGF overexpression in these groups caused lung injury in newborn rats, while anti-PGF antibody treatment signi ﬁcantly cured the hyperoxia-induced lung injury. Moreover, PGF overexpression signi ﬁcantly increased TNF-a and Il-6 levels in the bronchoalveolar lavage (BAL) ﬂuid of the Normoxia+Ad- PGF and Hyperoxia groups. However, their levels were signi ﬁcantly reduced in the BAL ﬂuid of the Hyperoxia+anti-PGF group. Immunohistochemical analysis revealed that PGF overexpression and hyperoxia treatment signi ﬁcantly increased the expression of the angiogenesis marker, CD34. However, its expression was signi ﬁcantly decreased upon administration of anti- PGF antibodies (compared to the control group under hyperoxia). In conclusion, PGF overexpression impairs lung development in newborn rats while its inhibition using an anti-PGF antibody ameliorates the same. These results provided new insights for the clinical management of bronchopulmonary dysplasia in premature infants.
The glycemia of animals submitted to three con- secutives SE at P7, P8, P9 (group II) were not modi- fied, when compared with saline-treated animals. Animals submitted to SE at P17 (group III) showed hypoglycemia at 90, 120, 180 and 360 min, when c o m p a red with control animals. In contrast, animals at P21 (group IV) showed a hyperglycemia peak dur- ing the first 30 min of induced-SE. These results show- ed that in rats, during early stages of development, the blood glucose level was not modified by pilo- carpine-induced SE. Older animals such as those in P21 already showed a hyperglycemic peak, re s e m- bling that pattern observed in adult rats. These data are summarized in Table 1.
Amygdala hyperactivity was observed at very early stage of neuropathic pain in SNL rats in an electrophysiological experi- ment . Recent studies reported that functional interactions between the amygdala and the anterior cingulate cortex or the prefrontal cortex are involved in pain-related negative emotions and cognition [17,18]. Amygdala blockade by the IBO lesion at the very early stage probably inhibited the initiation of these amygdala-related inter-brain region interactions, then reduced negative emotions, and thus could interfere with pain perception and pain chronicity. In addition, enhanced synaptic transmission between parabrachial nuclei–CeA and CeA–BLA was observed in rats with neuropathic pain . It is well known that the neural plasticity in the BLA is very important in fear memory . The amygdala also processes pain sensory information . Therefore, one possibility is that the amygdala processes pain information and forms pain-related memory template at the early stage after nerve injury. On the contrary, at the late stage in chronic pain after nerve injury, i.e. when pain memory has been established and when the vicious circle has begun between negative emotions and pain, the amygdala lesion hardly prevents chronic pain develop- ment and maintenance. Additionally, as previous finding suggested that hypertrophy and cell proliferation in the CeA and the BLA is associated with depression-like behavior in SNI neuropathic pain rats , blockage of amygdala activity may alleviate depression, which in return to facilitate the development of chronic pain .
Methodology/Principal Findings: Five-week-old male Wistar rats were given a semi-purified diet with or without 30 g/kg diet of the S-IMO (DP = 3.3), L-IMO (DP = 8.4), or Dex (DP = 1230) for two weeks. Dextran sulfate sodium (DSS) was administered to the rats for one week to induce experimental colitis. We evaluated the clinical symptoms during the DSS treatment period by scoring the body weight loss, stool consistency, and rectal bleeding. The development of colitis induced by DSS was delayed in the rats fed S-IMO and Dex diets. The DSS treatment promoted an accumulation of neutrophils in the colonic mucosa in the rats fed the control, S-IMO, and L-IMO diets, as assessed by a measurement of myeloperoxidase (MPO) activity. In contrast, no increase in MPO activity was observed in the Dex-diet-fed rats even with DSS treatment. Immune cell populations in peripheral blood were also modified by the DP of ingested saccharides. Dietary S-IMO increased the concentration of n-butyric acid in the cecal contents and the levels of glucagon-like peptide-2 in the colonic mucosa.
than the IP group because serum protein concentration tended to be higher at 30 min after β LG oral administration (60 min after AR induction) and disappeared faster. The collection of samples earlier than 30 min should confirm this suggestion and can shed some light as to whether there is any difference in intestinal permeability when OVA is given orally after the i. p. immunization. AR-induced behavioral changes were quantified by the decrease in motor ac- tivity as performed in a previous study , instead of using the classical score systems which require the subjective validation by the investigator [71,72]. The results after AR induction re- vealed a clear decrease of movements in comparison with the basal ones. However, when com- paring the motor activity between the IP and FA groups, it could be observed that the decrease in motor activity induced by AR was similar in both groups. Therefore, from the results ob- tained after AR induction, it could be concluded that only the serum concentrations of RMCP-II, which were highly increased by oral OVA, clearly indicated the development of an FA model. Further studies on intestinal permeability should be directed to elucidate changes induced by oral allergen administration in this FA model. However, the decrease in body tem- perature and also in motor activity did not differ between IP and FA rats, which could be attrib- uted to the similar serum IgE levels present at the end of the study.
The present study evaluated the effects of postnatal intermittent hypoxia on locomotor activity and neuronal cell survival in early adulthood rats. During a critical period of brain development on postnatal day (PD) 7-11, male rat pups were exposed to intermittent hypoxia and randomly assigned to three experimental groups: (1) intermittent hypoxia, (2) normoxia, and (3) control (unhandled). One and a half months later on PD56, a behavioral test was conducted, and cell survival was estimated in the hilus, dental gyrus, and CA1 and CA3 subfields of the hippocampus, nucleus accumbens shell and core, dorsal and ventral striatum, and prefrontal cortex. Our results showed that intermittent hypoxia produced hyperactivity that correlated well with psychomotor agitation observed in patients with schizophrenia. Moreover, post-hypoxic rats exhibited a reduction of the number of neurons in the hilar region of the hippocampus and dorsal striatum, structures that have been neuropathologically associated with schizophrenia.These findings suggest that intermittent hypoxia can modify the pattern of locomotor activity and selectively affect neurons in rats tested in early adulthood. Keywords: hypoxia, neurodevelopment, hyperactivity, cell survival, schizophrenia.
Female Wistar rats from our breeding colony weighing approximately 200 g were mated overnight to males of the same stock, in a harem system. Vaginal smears were collected and the presence of sperm was used to determine gestational day 0. Ten to 12 pregnant dams per group were exposed to either 8 or 16 mg/kg of fluoxetine (F8 or F16) or 40 or 80 mg/kg of venlafaxine (V40 or V80) administered intragastrically by ga- vage from gestational day 15 to 20. A control group (C) was gavaged with the vehicle (wa- ter). Food and water consumption during treatment was recorded. Doses of fluoxetine were selected from a previous experimental study on the embryotoxicity of fluoxetine carried out on rats (14). In this study, the developmental no observed adverse effect level (NOAEL) was 12.5 mg/kg. We chose 8 and 16 mg/kg dose levels which were lower and slightly higher than the NOAEL for embryotoxicity in order to look for the po- tential functional toxicity of lower doses and in order to obtain information for the design of future studies on behavioral teratology. Functional and behavioral toxicity is assumed to occur at dose levels lower than those involved in embryotoxicity. Less informa- tion was available on the developmental ef- fects of venlafaxine. Therefore, we based our dose selection on the information from the manufacturer referring to experimental studies in which the only toxic effect re- ported was delayed rat development at the dose of 80 mg/kg. In our study we selected 40 and 80 mg/kg. Thus, we used a weight ratio of 5:1 for venlafaxine and fluoxetine in the present study. It should be pointed out that this same proportion of doses is reported in clinical practice (maximum dose levels of 80 mg/day and 275 mg/day for fluoxetine and venlafaxine, respectively).
ERa is regarded as the one of the main targets responsible for the anti-obesity effects of E2 based on its expression levels in human subcutaneous WAT  as well as the results of a study using E2 inhibitor . The present study supports these results, as exogenous E2 led to increased expression of ERa for the stimulation of estrogenic signaling in normal SD rats. Schlegel et al. (1999) identified CAV1 as a potential regulator of ERa signal transduction by observing ligand-independent translocation of ERa into the nucleus upon co-expression of CAV1 and ERa. Conversely, the role of ERb in the development of obesity remains controversial [75,76]. A recent report demonstrated that ERb agonist treatment reduces adipogenic potential via negative crosstalk with PPARc in female OVX Wistar rats . In this study, abdominal WAT of E2-treated groups showed higher expression of ERb, with females more prominently affected. However, in the case of BAT, stimulation of ERb expression was observed only in females, which in turn may result in negative crosstalk of PPARc-dependent lipogenic potential in these groups . In case of BAT as well as gonadal and inguinal adipose tissues of male groups, ERb failed to show any distinct pattern, suggesting a specific differential expression pattern for adipose tissues (Figure 5).
Some studies have shown that G-CSF alters the course of LV remodeling. In a swine model of MI, G- CSF treatment reduced infarct size and improved cardiac function . In addition, Sugano et al.  observed that the acceleration of the healing process in the infarct zone mediated by G-CSF treatment led to decreased ventricular expansion in infarcted rats. It was also demonstrated that long-term use of low-dose G-CSF improved cardiac function . It has not yet been determined, however, if the effects of G-CSF in the acute phase of myocardial infarction are effective in altering post-infarction remodeling. Thus, our purpose in the present study was to test the effects of G-CSF in the acute infarct phase and its repercussions for the development of heart failure.
Diabetic nephropathy is one of the most common complications of diabetes and is characterized by increased urinary protein and loss of renal function. A number of studies have now definitely proven that improved metabolic control that achieves near-normoglycemia can significantly decrease the development and progression of diabetic nephropathy (Mogensen, 1984; Lee et al., 1995; Park et al., 1998). The metabolic factors such as AGEs, sorbitol beyond blood glucose level are also implicated in the pathogenesis of diabetic nephropathy (Schrijvers et al., 2004). Traditional plant remedies have been used for centuries in the treatment of diabetes (Akhtar et al., 1984; Kesari et al., 2005; Kesari et al., 2007; Rai et al., 2007), but only few of these plants have been scientifically evaluated. Therefore, we have investigated the effect of APSAE on glycemic and renal protection in STZ- induced diabetic rats. A. pavonina seed aqueous extract showed a dose dependent effect on fasting blood glucose in diabetic rats. The capacity of APSAE to decrease the elevated blood glucose to normal level is an essential trigger for the liver to revert to its
For the ﬁrst time we present a temporal proﬁle of the underlying cardiovascular autonomic changes that occur in the Goldblatt model of hypertension during 6 weeks in conscious condition. Some studies have suggested a role for changes in renal sympathetic tone in the 2K-1C hypertension. Indeed, renal denervation has been reported to ameliorate hypertension in Goldblatt animals (Katholi et al., 1982). Nakada et al. (1996) reported that suppression of sympathetic activity appears to depress the development of 2K-1C Goldblatt hyper- tension mainly after 4 weeks post-clipping, which is consistent with our data of elevations in sympathetic activity at this time. Indeed, there is evidence in renovascular hypertension that decreased renal blood ﬂow leads to elevated sympathetic nerve activity in humans (Johansson et al., 1999). This is analogous to human data indicating a role for renal afferents in exciting sympathetic efferent activity in re- fractory hypertension (Krum et al., 2009) Recently, we reported that 6 weeks after renal artery clipping in rats, the 2K-1C group showed a signiﬁcant increase in renal sympathetic nerve activity (RSNA) (and ar- terial pressure) when compared with the control group in urethane- anaesthetized rats (Oliveira-Sales et al., 2008).
To address these questions, it is important to use animal models with human PAH-like lesions, because of the limitations in obtaining tissue samples at various disease stages from pa- tients with PAH. In addition, tissue samples, appropriately processed for immunohistochemi- cal analyses with multiple SMC markers (ie, methanol-Carnoy’s fixed paraffin sections), may be required for the current phenotyping of SMC in vivo. [5,6,8–10,14,15] Recently, a new human PAH-like rat model accompanied by intimal and plexiform lesions, which mimic pul- monary vasculopathy in human PAH, was reported.  In this model, a single injection of a vascular endothelial growth factor (VEGF) receptor blocker Sugen 5416 in combination with chronic hypoxia for 3 weeks induced ‘progressive’ occlusive pulmonary vasculopathy with plexiform lesions, in contrast with ‘non-progressive’ pulmonary vasculopathy in rats exposed to chronic hypoxia alone. [17,18] Although apoptosis-resistant endothelial cells are believed to play a predominant role in the development of such obstructive pulmonary vasculopathy, [19,20] information regarding immature SMCs and inflammatory cells in these specific lesions, as well as related inflammatory gene expression in the lungs, is limited. This may preclude the opportunity to investigate the role of these cellular components in this model.
It has been suggested that, in some cases, exposure to environmental contaminants affects children more profoundly than adults. It is important to evaluate adverse health outcomes in children, a population susceptible to toxic chemicals and mixtures. We examined the effects that maternal exposure to two pesticides had on maturational aspects of offspring development during the nursing period. Nursing female rats were exposed to 1–4 mg/kg of intraperitoneal methamidophos, 200–800 mg/kg of chlorothalonil, or both. The higher doses of methamidophos affected pup viability by day 21 of life. Both pesticides, alone or together, affected body weight gain of dams and offspring. Developmental milestones evaluated in the pups were incisor eruption, ear unfolding, eye opening and testis descent. Although no clear dose–response relationship was established between these milestones and exposure to methamidophos or chlorothalonil, incisor eruption was accelerated in many groups, and the majority of rat offspring exposed to methamidophos presented later ear unfolding and eye opening than did the control group offspring. Sexual maturation (testis descent) was signiﬁcantly delayed in some groups. For dams and pups alike, simultaneous exposure to both pesticides was not found to have a greater toxic effect than that resulting from exposure to only one of the two. Taken together, these results demonstrate exposure-related inﬂuences on several developmental measures. Detection of more subtle effects may be improved through the use of the developmental temporal response protocols utilized in this study. r 2006 Elsevier GmbH. All rights reserved.
support the idea that beneficial effects in the developing brain depend upon low intensities of exercise . On the other hand, the high-, but not the low-, intensity exercise paradigm resulted in a significant increase of proliferative cell density in rats trained from P31 to P40. These findings reveal that new cell formation may vary according to exercise intensity and developmental stage of the brain. It is important to point out that new cell formation induced by exercise in these early stages could have a significant impact on brain structure and functional development. Studies in adult animals have shown that physical exercise enhances cell prolifera- tion and survival in the dentate gyrus and increases the magnitude of hippocampal LTP and improves spatial learning and memory [14,25]. Considering that new cell formation in the hippocam- pal region is most prevalent in early life , we speculate that exercise-induced cellular proliferation in these animals may also be accompanied by improved cognitive capability. Nevertheless, further studies are needed to establish this relationship between exercise intensity, cell proliferation and cognitive functions during postnatal brain development.
However, since periodontal disease onset takes place without the presence of ligatures or bacterial injection, it is possible that changes in the oral flora, or even in inflammatory immune response raised against oral bacteria may be involved in initiating the disease. It is also important to consider that AGEs accumulation in periodontal tissue could be involved in the development of inflammatory reaction and alveolar bone loss presented by the diabetic rats . Another possible reason for the transitory bone resorptive activity in periodontium of diabetic mice may be the development of immunoregulatory mechanisms, which are thought to prevent or attenuate alveolar bone loss [33,34].
Metronidazole is an antiprotozoal and antibacterial used in gynecology and obstetrics for the treatment of parasitic infections. However, despite having clinical use for more than three decades, questions about the safety of its use during pregnancy is not well understood. Thus, the present study evaluated the effect of metronidazole on placental and fetal development in pregnant rats. Metronidazole was orally administered by gavage at a dosage of 130 mg/kg for 7 and 14 days. Morphological analysis, morphometry and immunohistochemistry were performed at the implantation sites and placentas with 14 days of development. The results showed that in the treated group there was a significant reduction in the number of implantation sites, total placental disc area and constituent elements of the labyrinth and spongiotrophoblast layers. Histochemical analysis revealed no significant changes in the content of collagen, elastic and reticular fibers. The TUNEL test showed apoptotic activity in the implantation sites and placentas with 14 days of development independent of the treatment. There was no evidence of malformation in the neonates. However, there was a significant reduction in the number and weight of neonates in the group treated with metronidazole when compared to the control group. Thus, it is concluded that the administration of 130 mg/kg of metronidazole during pregnancy in rats, in addition to interfering with the number of implanted embryos, promotes changes in placental structure and interferes with fetal development. This suggests that this drug should be used with caution during pregnancy.
One of the ways to study the development of the CNS is to observe the ontogenesis of the reflex, since reflexes represent one of the behavioral expressions of brain function. Reflex ontogenesis encompasses visual, auditory and motor maturation, and can be affected by any environmental or organic stimulus, generating consequences for the formation of the nervous system (Soares et al. 2014). They are the result of stimuli and appear in certain periods of development, following a pre-determined order, according to the age of the animals (Deiró et al. 2008). The maturation of specific reflexes in rats has been well established, showing that disturbances at this stage of growth may point to insults in neurological development (Leite et al. 2002).
levels was observed in treated mothers compared to controls. The levels of measured hormones in the control and PTU-treated two months old rats were not significantly different. Ten percent of 60-day- old treated females did not reach estrus and they were sacrificed in diestrus. The secondary interstitial cells were the dominant structures in the ovaries. The number of healthy growing and early antral follicles was markedly decreased. Ovaries of treated rats contained relatively few antral follicles, significantly more atretic antral follicles and a decreased number of corpora lutea, compared to controls. These results indicate that lack of thyroid hormones during prenatal and early postnatal development impair ovarian development in rats.
All experimental procedures were performed on anesthetized rats. Anesthesia was maintained with ketamine and xylazine (60mg/Kg and 8mg/Kg i.p.). After properly anesthetized, the rats were set in an acrylic cylindrical compartment (Figure 1). They were transferred into a protected room which has the MDS Nordion Cobalt-60 source in the center. This room has a complex protection mechanism that rises the source from an enclosed cage from under the ground only when it is fully locked and safe. We developed a covering device (15cm-thick plumb bricks with a 32mm round opening in the center to provide a collimator) to protect the rest of the animal’s body from the radiation shade (Figure 2). This protective plumb device did not cover the back of the animal, in order to allow radiation to disperse after collimation and prevent it from reflecting and spreading in the surrounding tissues (Figure 3). A TLD dosimetry system was used in the pilot experiment so as to check the proper radiation dose in the irradiated field and it also proved that the dose outside the radiation beam was lower than 1% of the dose inside it. The beam axis was determined using a laser, in order to center and align the collimator to the source (Figure 4). The total radiation