93 research outputs found
Erythropoietin Attenuates Brain Injury, Subventricular Zone Expansion, and Sensorimotor Deficits in Hypoxic-Ischemic Neonatal Rats
The aim of this study was to investigate the effect of erythropoietin (EPO) on histological brain injury, subventricular zone (SVZ) expansion, and sensorimotor function deficits induced by hypoxia-ischemia (HI) in newborn rat pups. Seven-day-old male rat pups were divided into six groups: normoxia control, normoxia EPO, hypoxia control, hypoxia EPO, HI control, and HI EPO group. Sham surgery or HI was performed in all animals. HI was induced by ligation of the right common carotid artery followed by 90 min of hypoxia with 8% oxygen. Recombinant human EPO 3 U/g or saline was administered intraperitoneally, immediately, at 24- and 48-hr after insult. At two weeks after insult, animals were challenged with cylinder-rearing test for evaluating forelimb asymmetry to determine sensorimotor function. All animals were then sacrificed for volumetric analysis of the cerebral hemispheres and the SVZ. The saline-treated HI rats showed marked asymmetry by preferential use of the non-impaired, ipsilateral paw in the cylinder-rearing test. Volumetric analysis of brains revealed significantly decreased preserved ipsilateral hemispheric volume and increased ipsilateral SVZ volume compared with the sham-operated animals. Treatment of EPO significantly improved forelimb asymmetry and preserved ipsilateral hemispheric volume along with decreased expansion of ipsilateral SVZ following HI compared to the saline-treated HI rats. These results support the use of EPO as a candidate drug for treatment of neonatal hypoxic-ischemic brain damage
The first description of severe anemia associated with acute kidney injury and adult minimal change disease: a case report
Maternal separation prior to neonatal hypoxia-ischemia: Impact on emotional aspects of behavior and markers of synaptic plasticity in hippocampus
Exposure to early-life stress is associated with long-term alterations in brain and behavior, and may aggravate the outcome of neurological insults. This study aimed at investigating the possible interaction between maternal separation, a model of early stress, and subsequent neonatal hypoxia-ischemia on emotional behavior and markers of synaptic plasticity in hippocampus. Therefore, rat pups (N = 60) were maternally separated for a prolonged (MS 180min) or a brief (MS 15min) period during the first six postnatal days, while a control group was left undisturbed. Hypoxia-ischemia was applied to a subgroup of each rearing condition on postnatal day 7. Emotional behavior was examined at three months of age and included assessments of anxiety (elevated plus maze), depression-like behavior (forced swimming) and spontaneous exploration (open field). Synaptic plasticity was evaluated based on BDNF and synaptophysin expression in CA3 and dentate gyrus hippocampal regions. We found that neonatal hypoxia-ischemia caused increased levels of anxiety, depression-like behavior and locomotor activity (ambulation). Higher anxiety levels were also seen in maternally separated rats (MS180min) compared to non-maternally separated rats, but prolonged maternal separation prior to HI did not potentiate the HI-associated effect. No differences among the three rearing conditions were found regarding depression-like behavior or ambulation. Immunohistochemical evaluation of synaptophysin revealed that both prolonged maternal separation (MS180min) and neonatal hypoxia-ischemia significantly reduced its expression in the CA3 and dentate gyrus. Decreases in synaptophysin expression in these areas were not exacerbated in rats that were maternally separated for a prolonged period prior to HI. Regarding BDNF expression, we found a significant decrease in immunoreactivity only in the hypoxic-ischemic rats that were subjected to the prolonged maternal separation paradigm. The above findings suggest that early-life stress prior to neonatal hypoxia-ischemia leads to significant alterations in synaptic plasticity of the dorsal hippocampus during adulthood, but does not exacerbate HI-related changes in emotional behavior
The neuroprotective effect of recombinant human erythropoietin via an antiapoptotic mechanism on hypoxic-ischemic brain injury in neonatal rats
PurposeThe neuroprotective effects of erythropoietin (EPO) have been recently shown in many animal models of brain injury, including hypoxic-ischemic (HI) encephalopathy, trauma, and excitotoxicity; however, limited data are available for such effects during the neonatal periods. Therefore, we investigated whether recombinant human EPO (rHuEPO) can protect against perinatal HI brain injury via an antiapoptotic mechanism.MethodsThe left carotid artery was ligated in 7-day-old Sprague-Dawley (SD) rat pups (in vivo model). The animals were divided into 6 groups: normoxia control (NC), normoxia sham-operated (NS), hypoxia only (H), hypoxia+vehicle (HV), hypoxia+rHuEPO before a hypoxic insult (HE-B), and hypoxia+rHuEPO after a hypoxic insult (HE-A). Embryonic cortical neuronal cell culture of SD rats at 18 days gestation (in vitro model) was performed. The cultured cells were divided into 5 groups: normoxia (N), hypoxia (H), and 1, 10, and 100 IU/mL rHuEPO-treated groups.ResultsIn the in vivo model, Bcl-2 expressions in the H and HV groups were lower than those in the NC and NS groups, whereas those in the HE-A and HE-B groups were greater than those of the H and HV groups. The expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were in contrast to those of Bcl-2. In the in vitro model, the patterns of Bcl-2, Bax, and caspase-3 expression and Bax/Bcl-2 ratio were similar to the results obtained in the in vivo model.ConclusionrHuEPO exerts neuroprotective effect against perinatal HI brain injury via an antiapoptotic mechanism
Experimental modeling of hypoxia in pregnancy and early postnatal life
The important role of equilibrium of environmental factors during the embryo-fetal period is undisputable. Women of reproductive age are increasingly exposed to various environmental risk factors such as hypoxia, prenatal viral infections, use of drugs, smoking, complications of birth or stressful life events. These early hazards represent an important risk for structural and/or functional maldevelopment of the fetus and neonates. Impairment of oxygen/energy supply during the pre- and perinatal period may affect neuronal functions and induce cell death. Thus when death of the newborn is not occurring following intrauterine hypoxia, various neurological deficits, including hyperactivity, learning disabilities, mental retardation, epilepsy, cerebral palsy, dystonia etc., may develop both in humans and in experimental animals. In our animal studies we used several approaches for modeling hypoxia in rats during pregnancy and shortly after delivery, i.e. chronic intrauterine hypoxia induced by the antiepileptic drug phenytoin, neonatal anoxia by decreased oxygen saturation in 2-day-old pups. Using these models we were able to test potential protective properties of natural (vitamin E, melatonin) and synthetic (stobadine) compounds. Based on our results, stobadine was also able to reduce hypoxia-induced hyperactivity and the antioxidant capacity of stobadine exceeded that of vitamin E and melatonin, and contrary to vitamin E, stobadine had no adverse effects on developing fetus and offspring
Erythropoietin: a multimodal neuroprotective agent
The tissue protective functions of the hematopoietic growth factor erythropoietin (EPO) are independent of its action on erythropoiesis. EPO and its receptors (EPOR) are expressed in multiple brain cells during brain development and upregulated in the adult brain after injury. Peripherally administered EPO crosses the blood-brain barrier and activates in the brain anti-apoptotic, anti-oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular endothelial cells and stimulates angiogenesis and neurogenesis. These mechanisms underlie its potent tissue protective effects in experimental models of stroke, cerebral hemorrhage, traumatic brain injury, neuroinflammatory and neurodegenerative disease. The preclinical data in support of the use of EPO in brain disease have already been translated to first clinical pilot studies with encouraging results with the use of EPO as a neuroprotective agent
ENVIRONMENTAL ENRICHMENT PROTECTS AGAINST DECREASED EXPRESSION OF HIPPOCAMPAL SYNAPTOPHYSIN AND GFAP IN RATS EXPOSED TO CHRONIC UNPREDICTABLE STRESS: THE ROLE OF SEX
Exposure of immunologically naive laboratory rodents to antigen via the airways. Where does tolerance stop and sensitization begin?
Conventional rodent models of respiratory allergy that employ
intraperitoneal sensitization to aeroallergen plus adjuvant, have
offered greatly to our current knowledge of the pathophysiology of
allergic airway diseases. Notwithstanding this significant contribution,
non-adjuvant aided sensitization via respiratory presentation of the
allergen, is more naturally relevant and more closely mimics the human
exposure. Nevertheless, in the experimental setting, primary respiratory
exposure to inert antigen is likely to lead to inhalation tolerance.
Inasmuch as divergent and discrepant results are often reported in
experimental models employing this method of sensitization, we set out
to review the relative literature and identify and discuss factors that
are liable to interfere in such protocols and modify the immune
response, hence leading to variable outcomes. Protocol design features
(including the use of anaesthesia, the nature and dosage of the antigen
and the strain/age/sex and handling of the animals) as well as
environmental factors (including airborne substances, viruses and
lipopolysaccharide) have been identified as key modulators of the immune
response that evolves, following primary airway exposure of laboratory
rodents to aeroallergen. Delineation of the effect of those factors to
induction or abrogation of inhalation tolerance can have important
implications in the design of both improved experimental protocols of
respiratory allergy and methods to intercept sensitization to inert
aeroallergens in the clinical field
Efficiency of different decalcification protocols for nasal osseous structures in a rat experimental model of allergic rhinitis, and their effects on epithelial histology: An attempt at standardization
Introduction: Decalcification of osseous specimens is required for histological analysis; this however may cause tissue damage. In rodent models of allergic rhinitis (AR), epithelial histologic assessment necessitates prior decalcification of the nasal osseous structures. However, respiratory epithelium is highly susceptible to damage, and rat nasal architecture is elaborate and its sectioning is challenging. Nevertheless, decalcification is not standardized in experimental AR. We therefore undertook this task, in order to reduce experimental bias. Methods: Six-to-eight week-old Wistar rats underwent an AR protocol. Subsequently, nasal structures were decalcified in the following mediums: (i) formic acid 10% for 5 and 20 days; (ii) formic acid 15% for 5 and 15 days; (iii) Morse Solution for 5 and 20 days and (iv) EDTA for 20 and 40 days. Decalcification efficiency/speed was evaluated via radiographic analysis. Furthermore, specimens were stained with hematoxylin and eosin and assessed for preservation of epithelial features. Results: Specimens were appropriately decalcified in 5 days in the formic acid-based mediums and in 20 days in EDTA with minimal epithelial damage. EDTA for 40 days had no unacceptable adverse effects; conversely, 15 and/or 20 days in acid-based agents provided no extra benefit for decalcification and were detrimental to the epithelium. Conclusions: EDTA treatment for 20 days is appropriate for decalcification of nasal structures in rat models of allergic rhinitis; further incubation preserves epithelial integrity but is not required. When urgency is a factor, formic-acid-based decalcification for 5 days yields acceptable results. © 2014 Elsevier GmbH
N-acetylcysteine exerts therapeutic action in a rat model of allergic rhinitis
Background The pathophysiologic mechanism of allergy is dependent on the
action of many redox-sensitive proinflammatory mediators. However, even
though redox disturbances are believed to be a hallmark of inflammation,
little is known of the effect of redox imbalance to the pathophysiology
of allergic rhinitis. We thus opted to investigate the relation of
oxidative stress and allergic rhinitis, through the utilization of a
potent antioxidant substance (N-acetylcysteine [NAC]) in a rat model
of allergic rhinitis and the evaluation of its action on specific
markers of inflammation.
Methods NAC (50 mg/kg and 250 mg/kg) was intraperitoneally administered
to ovalbumin (OVA)-sensitized rats prior to intranasal challenge with
OVA. Mucosal congregation of inflammatory cells (eosinophils and mast
cells), mucosal expression of redox-sensitive enzymes (inducible nitric
oxide synthase [iNOS] and cyclooxygenase 2 [COX-2]), and the blood
levels of a key proinflammatory mediator (tumor necrosis factor-alpha
[TNF-alpha]) were evaluated.
Results Intranasal OVA challenges lead to mucosal inflammation,
induction of the mucosal expression of iNOS and COX-2 and elevation of
TNF-alpha blood levels. NAC significantly inhibited accumulation of
inflammatory cells and downregulated iNOS expression and TNF-alpha serum
levels. The role of COX-2 appeared to be 2-fold and its expression was
divergently modulated by NAC.
Conclusion Our findings suggest that redox balance is involved in the
pathophysiology of allergic rhinitis in rats and that NAC can
potentially suppress the allergen-induced nasal inflammatory cascade.
The investigation of the role of oxidative stress in atopy could help in
the evaluation of the therapeutic potential of antioxidant substances in
allergic diseases. (C) 2013 ARS-AAOA, LLC
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