Injury In Adult Rats Research Articles

Effect of dexmedetomidine on ncRNA and mRNA profiles of cerebral ischemia-reperfusion injury in transient middle cerebral artery occlusion rats model.

Ischemic stroke poses a significant global health burden, with rapid revascularization treatments being crucial but often insufficient to mitigate ischemia-reperfusion (I/R) injury. Dexmedetomidine (DEX) has shown promise in reducing cerebral I/R injury, but its potential molecular mechanism, particularly its interaction with non-coding RNAs (ncRNAs), remains unclear. This study investigates DEX's therapeutic effect and potential molecular mechanisms in reducing cerebral I/R injury. A transient middle cerebral artery obstruction (tMACO) model was established to simulate cerebral I/R injury in adult rats. DEX was administered pre-ischemia and post-reperfusion. RNA sequencing and bioinformatic analyses were performed on the ischemic cerebral cortex to identify differentially expressed non-coding RNAs (ncRNAs) and mRNAs. The sequencing results showed 6,494 differentially expressed (DE) mRNA and 2698 DE circRNA between the sham and tMCAO (I/R) groups. Additionally, 1809 DE lncRNA, 763 DE mRNA, and 2795 DE circRNA were identified between the I/R group and tMCAO + DEX (I/R + DEX) groups. Gene ontology (GO) analysis indicated significant enrichment in multicellular biogenesis, plasma membrane components, and protein binding. KEGG analysis further highlighted the potential mechanism of DEX action in reducing cerebral I/R injury, with hub genes involved in inflammatory pathways. This study demonstrates DEX's efficacy in reducing cerebral I/R injury and offers insights into its brain-protective effects, especially in ischemic stroke. Further research is warranted to fully understand DEX's neuroprotective mechanisms and its clinical applications.

Effect of Lactoferrin versus Dexamethasone on Induced Acute Lung Injury in Adult Rat: A Histological Study

Abstract Introduction acute lung injury (ALI) is one of the most critical illnesses affecting the lung and is commonly associated with severe complications. management of ALI without major side effects remains a continuous challenge. Lactoferrin (LF) is an iron-binding glycoprotein having potential anti-inflammatory effects. Aim the study was conducted to compare the therapeutic role of lactoferrin (LF) versus dexamethasone (DEXA) on the microscopic structure of the lung in a model of lipopolysaccharide (LP) induced acute lung injury. Material and Methods thirty-five adult male albino rats weighing (180-200gm) were divided randomly into 4 groups. Group I (control group), Group II (LP group): rats received a single IP injection of Lipopolysaccharide (3mg/kg). Group III (LP+LF group): rats received LP as in group II followed one hour later by IP injection of lactoferrin (5mg/rat). Group IV (LP+DEXA group): rats received LP as in group II followed one hour later by IP injection of dexamethasone (5mg/kg). after 24 hours, lung specimens were proceeded for light microscopic examination, as well as Morphometrical and statistical analyses. Results H&E-stained section of Group II showed marked inflammatory changes, interalveolar septa were significantly thickened and were heavily infiltrated with inflammatory cells and extravasated red blood cells were occasionally detected. Many alveoli appeared collapsed. The lining epithelium of bronchi appeared occasionally desquamated and peri-bronchial lymphoid aggregation were observed. An apparent increase in mucus production and significant increase in number of goblet cells were detected by PAS-stain. Orcein-stained section showed disruption of elastic fibers. immunohistochemical stain revealed a significantly increased reaction to iNOS antibodies. On the other hand, the lung structure in group III and group IV were much more improved, with group IV very similar to the control group. Conclusion Both lactoferrin and dexamethasone showed therapeutic and anti-inflammatory effects in LP induced ALI. These effects were more prominent in dexamethasone than lactoferrin as detected by microscopic, morphometric, and statistical studies.

Lactoferrin versus Dexamethasone in a Model of Acute Lung Injury in Adult Rat: Histological and Immunohistochemical Study

Lactoferrin versus Dexamethasone in a Model of Acute Lung Injury in Adult Rat: Histological and Immunohistochemical Study

An Evaluation of the Effectiveness of Melatonin and n-Acetylcysteine in Cerebral Ischemia-Reperfusion Injury in Adult Rats.

Background and Objectives: The purpose of this study was to apply histopathological and immunohistochemical methods to compare the protective efficacy of melatonin and N-acetylcysteine (NAC) application in rats with experimental brain ischemia/reperfusion (I/R) injury induced through occlusion of the middle cerebral artery (MCA), and to evaluate the protective effect of their combined use. Materials and Methods: Forty-one young adult male Wistar albino rats were divided into five groups-control (n = 8), I/R group (n = 8), melatonin (n = 8), NAC (n = 8), and melatonin + NAC (n = 9). Results: All scores differed between the groups, apart from vascular congestion (p < 0.05). At two-way comparisons, all histological scores were significantly higher in the I/R group than in the control group (p < 0.05). No change occurred in the vascular congestion scores with the administration of melatonin, although decreases were determined in all other scores. These decreases were statistically significant for cellular eosinophilic pyknotic degeneration, vacuolization, and edema (p < 0.05). All histopathological scores in the group administered NAC together with melatonin were significantly lower than in the I/R group (p < 0.05). Conclusions: The combined use of NAC and melatonin, the neuroprotective efficacy of which on histopathological parameters is shown in this study, now needs to be supported by further research.

NDRG2 regulates the formation of reactive astrocyte-derived progenitor cells via Notch signaling pathway after brain traumatic injury in rats.

In response to traumatic brain injury, a subpopulation of cortical astrocytes is activated, resulting in acquisition of stem cell properties, known as reactive astrocytes-derived progenitor cells (Rad-PCs). However, the underlying mechanisms remain largely unknown during this process. In this study, we examined the role of N-myc downstream-regulated gene 2 (NDRG2), a differentiation- and stress-associated molecule, in Rad-PCs after cortical stab injury in adult rats. Immunohistochemical analysis showed that in the cerebral cortex of normal adult rats, NDRG2 was exclusively expressed in astrocytes. After liu cortical injury, the expression of NDRG2 was significantly elevated around the wound and most cells expressing NDRG2 also expressed GFAP, a reactive astrocyte marker. Importantly, NDRG2-expressing cells were co-labeled with Nestin, a marker for neural stem cells, some of which also expressed cell proliferation marker Ki67. Overexpression of NDRG2 further increased the number of NDRG2/Nestin double-labeling cells around the lesion. In contrast, shRNA knockdown of NDRG2 decreased the number of NDRG2+/Nestin+ cells. Intracerebroventricular administration of stab-injured rats with a Notch antagonist, DAPT, led to a significant decrease in Nestin+/NDRG2+ cells around the injured boundary, but did not affect NDRG2+ cells. Moreover, overexpression or knockdown of NDRG2 led to up- and down-regulation of the expression of Notch intracellular domain NICD and Notch target gene Hes1, respectively. Taken together, these results suggest that NDRG2 may play a role in controlling the formation of Rad-PCs in the cerebral cortex of adult rats following traumatic injury, and that Notch signaling pathway plays a key role in this process.

Cervical spinal cord injury leads to injury and altered metabolism in the lungs.

High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality rates. While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury in adult rats. We demonstrate that animals display some early signs of lung injury two weeks post-spinal cord injury. While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury.

AAV Vector Mediated Delivery of NG2 Function Neutralizing Antibody and Neurotrophin NT-3 Improves Synaptic Transmission, Locomotion, and Urinary Tract Function after Spinal Cord Contusion Injury in Adult Rats.

NG2 is a structurally unique transmembrane chondroitin sulfate proteoglycan (CSPG). Its role in damaged spinal cord is dual. NG2 is considered one of key inhibitory factors restricting axonal growth following spinal injury. Additionally, we have recently detected its novel function as a blocker of axonal conduction. Some studies, however, indicate the importance of NG2 presence in the formation of synaptic contacts. We hypothesized that the optimal treatment would be neutralization of inhibitory functions of NG2 without its physical removal. Acute intraspinal injections of anti-NG2 monoclonal antibodies reportedly prevented an acute block of axonal conduction by exogenous NG2. For prolonged delivery of NG2 function neutralizing antibody, we have developed a novel gene therapy: adeno-associated vector (AAV) construct expressing recombinant single-chain variable fragment anti-NG2 antibody (AAV-NG2Ab). We examined effects of AAV-NG2Ab alone or in combination with neurotrophin NT-3 in adult female rats with thoracic T10 contusion injuries. A battery of behavioral tests was used to evaluate locomotor function. In vivo single-cell electrophysiology was used to evaluate synaptic transmission. Lower urinary tract function was assessed during the survival period using metabolic chambers. Terminal cystometry, with acquisition of external urethral sphincter activity and bladder pressure, was used to evaluate bladder function. Both the AAV-NG2Ab and AAV-NG2Ab combined with AAV-NT3 treatment groups demonstrated significant improvements in transmission, locomotion, and bladder function compared with the control (AAV-GFP) group. These functional improvements associated with improved remyelination and plasticity of 5-HT fibers. The best results were observed in the group that received combinational AAV-NG2Ab+AAV-NT3 treatment.SIGNIFICANCE STATEMENT We recently demonstrated beneficial, but transient, effects of neutralization of the NG2 proteoglycan using monoclonal antibodies delivered intrathecally via osmotic mini-pumps after spinal cord injury. Currently, we have developed a novel gene therapy tool for prolonged and clinically relevant delivery of a recombinant single-chain variable fragment anti-NG2 antibody: AAV-rh10 serotype expressing scFv-NG2 (AAV-NG2Ab). Here, we examined effects of AAV-NG2Ab combined with transgene delivery of Neurotrophin-3 (AAV-NT3) in adult rats with thoracic contusion injuries. The AAV-NG2Ab and AAV-NG2Ab+AAV-NT3 treatment groups demonstrated significant improvements of locomotor function and lower urinary tract function. Beneficial effects of this novel gene therapy on locomotion and bladder function associated with improved transmission to motoneurons and plasticity of axons in damaged spinal cord.

Circuit reconstruction of newborn neurons after spinal cord injury in adult rats via an NT3-chitosan scaffold.

An implanted neurotrophin-3 (NT3)-chitosan scaffold can recruit endogenous neural stem cells to migrate to a lesion region and differentiate into mature neurons after adult spinal cord injury (SCI). However, the identities of these newborn neurons and whether they can form functional synapses and circuits to promote recovery after paraplegia remain unknown. By using combined advanced technologies, we revealed here that the newborn neurons of several subtypes received synaptic input from the corticospinal tract (CST), rubrospinal tract (RST), and supraspinal tracts. They formed a functional neural circuit at the injured spinal region, further driving the local circuits beneath the lesion. Our results showed that the NT3-chitosan scaffold facilitated the maturation of spinal neurons and the reestablishment of the spinal neural circuit in the lesion region 12 weeks after SCI. Transsynaptic virus experiments revealed that these newborn spinal neurons received synaptic connections from the CST and RST and drove the neural circuit beneath the lesion via newly formed synapses. These re-established circuits successfully recovered the formation and function of the neuromuscular junction (NMJ) beneath the lesion spinal segments. These findings suggest that the NT3-chitosan scaffold promotes the formation of relay neural circuits to accommodate various types of brain descending inputs and facilitate functional recovery after paraplegia.

Downregulation of microRNA-124-3p promotes subventricular zone neural stem cell activation by enhancing the function of BDNF downstream pathways after traumatic brain injury in adult rats.

AimsIn this study, the effect of intracerebral ventricle injection with a miR‐124‐3p agomir or antagomir on prognosis and on subventricular zone (SVZ) neural stem cells (NSCs) in adult rats with moderate traumatic brain injury (TBI) was investigated.MethodsModel rats with moderate controlled cortical impact (CCI) were established and verified as described previously. The dynamic changes in miR‐124‐3p and the status of NSCs in the SVZ were analyzed. To evaluate the effect of lateral ventricle injection with miR‐124‐3p analogs and inhibitors after TBI, modified neurological severity scores (mNSSs) and rotarod tests were used to assess motor function prognosis. The variation in SVZ NSC marker expression was also explored. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of predicted miR‐124‐3p targets was performed to infer miR‐124‐3p functions, and miR‐124‐3p effects on pivotal predicted targets were further explored.ResultsAdministration of miR‐124 inhibitors enhanced SVZ NSC proliferation and improved the motor function of TBI rats. Functional analysis of miR‐124 targets revealed high correlations between miR‐124 and neurotrophin signaling pathways, especially the TrkB downstream pathway. PI3K, Akt3, and Ras were found to be crucial miR‐124 targets and to be involved in most predicted functional pathways. Interference with miR‐124 expression in the lateral ventricle affected the PI3K/Akt3 and Ras pathways in the SVZ, and miR‐124 inhibitors intensified the potency of brain‐derived neurotrophic factor (BDNF) in SVZ NSC proliferation after TBI.ConclusionDisrupting miR‐124 expression through lateral ventricle injection has beneficial effects on neuroregeneration and TBI prognosis. Moreover, the combined use of BDNF and miR‐124 inhibitors might lead to better outcomes in TBI than BDNF treatment alone.

The exogenous surfactant pre-treatment attenuates ventilator-induced lung injury in adult rats

Mechanical ventilation is an essential supportive therapy in the treatment of critical patients, and it aims to maintain adequate gas exchange; however, it can also contribute to inflammation and oxidative stress, thus leading to lung injury. We tested the hypothesis that exogenous surfactant administration will be protective against ventilator-induced lung injury in adult healthy Wistar rats both because of its anti-inflammatory properties as well as its role in preventing alveolar collapse at end-expiration. Thus, the effect of intranasal instillation of a bovine exogenous surfactant was tested in Wistar rats submitted to mechanical ventilation. The animals were divided into four groups: (1) CONTROL; (2) SURFACTANT; (3) Mechanical ventilation (MV); (4) MV with pre-treatment with surfactant (MVSURFACTANT). The MV and MVSURFACTANT were submitted to MV with high tidal volume (12 mL/kg) for 1 h. After the experimental protocol, all animals were euthanized and the arterial blood, bronchoalveolar lavage fluid and lungs were collected for biochemical, immunoenzymatic assay, arterial blood gases, and morphometric analyzes. The Wistar rats that received exogenous surfactant (Survanta®) by intranasal instillation before MV demonstrated reduced levels of leukocytes, inflammatory biomarkers such as CCL2, IL-1, IL-6 and TNF-α. Furthermore, it prevented oxidative damage by reducing lipid peroxidation and protein carbonylation as well as histological pattern changes of pulmonary parenchyma. Our data indicate that exogenous surfactant attenuated lung inflammation and redox imbalance induced by mechanical ventilation in healthy adult rats suggesting a preventive effect on ventilator-induced lung injury.

Spatial and temporal dynamics of HDACs class IIa following mild traumatic brain injury in adult rats.

The fundamental role of epigenetic regulatory mechanisms involved in neuroplasticity and adaptive responses to traumatic brain injury (TBI) is gaining increased recognition. TBI-induced neurodegeneration is associated with several changes in the expression-activity of various epigenetic regulatory enzymes, including histone deacetylases (HDACs). In this study, PET/CT with 6-([18F]trifluoroacetamido)-1- hexanoicanilide ([18F]TFAHA) to image spatial and temporal dynamics of HDACs class IIa expression-activity in brains of adult rats subjected to a weight drop model of diffuse, non-penetrating, mild traumatic brain injury (mTBI). The mTBI model was validated by histopathological and immunohistochemical analyses of brain tissue sections for localization and magnitude of expression of heat-shock protein-70 kDa (HSP70), amyloid precursor protein (APP), cannabinoid receptor-2 (CB2), ionized calcium-binding adapter protein-1 (IBA1), histone deacetylase-4 and -5 (HDAC4 and HDAC5). In comparison to baseline, the expression-activities of HDAC4 and HDAC5 were downregulated in the hippocampus, nucleus accumbens, peri-3rd ventricular part of the thalamus, and substantia nigra at 1-3 days post mTBI, and remained low at 7-8 days post mTBI. Reduced levels of HDAC4 and HDAC5 expression observed in neurons of these brain regions post mTBI were associated with the reduced nuclear and neuropil levels of HDAC4 and HDAC5 with the shift to perinuclear localization of these enzymes. These results support the rationale for the development of therapeutic strategies to upregulate expression-activity of HDACs class IIa post-TBI. PET/CT (MRI) with [18F]TFAHA can facilitate the development and clinical translation of unique therapeutic approaches to upregulate the expression and activity of HDACs class IIa enzymes in the brain after TBI.

The GDF11 Promotes Nerve Regeneration After Sciatic Nerve Injury in Adult Rats by Promoting Axon Growth and Inhibiting Neuronal Apoptosis.

Introduction: Sciatic nerve injury is a common injury of the nervous system. Stem cell-based therapies, drug-based therapies and rehabilitation physiotherapy therapies are currently available, but their limited therapeutic efficacy limits their use. Here, we aimed to explore a novel lentiviral-based gene therapeutic strategy and to elaborate its mechanism. Materials and Methods: Recombinant GDF11 protein was used for the in vitro treatment of dorsal root ganglion (DRG) cells. Lentivirus was used to construct a vector system for the in vivo expression of GDF11. The nerve conduction function was detected using action-evoked potentials at different time periods, and the regulatory effect of nerves on target organs was detected by weighing the gastrocnemius muscle. Immunofluorescence of NF200 and S100 was used to show the regeneration of the sciatic nerve, and myelin and Nissl staining were performed to observe the pathological features of the tissue. Western was used to validate signaling pathways. The expression of related genes was observed by qPCR and Western blotting, and cell apoptosis was detected by flow cytometry. Result: GDF11 promotes the axonal growth of DRG cells and inhibits DGR cell apoptosis in vitro. GDF11 acts by activating the Smad pathway. GDF11 promotes the recovery of damaged sciatic nerve function in rats, the regeneration of damaged sciatic nerves in rats, and myelin regeneration of damaged sciatic nerves in rats. GDF11 also exerts a protective effect on neuronal cells in rats. Conclusion: Based on the present study, we conclude that GDF11 promotes axonal growth and inhibits DRG cell apoptosis in vitro through the Smad pathway, and lentivirus-mediated GDF11 overexpression in vivo can promote the recovery of sciatic nerves after transection by promoting axonal growth and inhibiting neuronal apoptosis in the spinal cord.

Functional and structural assessment of the possible protective effect of platelet-rich plasma against ischemia/reperfusion-induced ovarian injury in adult rats.

This study aimed to evaluate the possible protective effect of platelet-rich plasma (PRP) on ischemia reperfusion (I/R)-induced ovarian injury in a rat model. Forty adult female albino rats were randomly assigned to four groups: control, ischemia, I/R, and I/R + intraperitoneal PRP. Induction of ischemia was done by bilateral ovarian torsion for 3 h, while reperfusion was done by subsequent detorsion for another 3 h. PRP was injected 30 min before detorsion. Histological assessment and measurement of ovarian anti-Mullerian hormone (AMH) were done to assess the degree of tissue damage and the remaining ovarian reserve. Ovarian malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured to evaluate the oxidant-antioxidant balance. Tumor necrosis factor-α (TNF-α) was measured to assess degree of inflammation. Immunohistochemical assessment of ovarian vascular endothelial growth factor-A (VEGF-A) was also done. PRP treated I/R group revealed a significant decrease in MDA (P = 0.007), TNF-α (P = 0.001), and a significant increase in TAC (P = 0.001) and VEGF-A (P = 0.003) in comparison to the untreated I/R group. Furthermore, limited vascular congestion and inflammatory infiltration were observed after PRP treatment. However, no significant difference was detected in AMH after PRP treatment. Our results denoted that PRP may help in preservation of ovarian function and structure during surgical conservative detorsion of the torsioned ovary. These protective effects could be attributed to its ability to reduce oxidative stress, inflammation and also to its high content of growth factors especially VEGF.

Downregulation of Nck1 After Spinal Cord Injury in Adult Rats

Background:Nck1 is an important molecule that participates in many cellular processes, including neurite outgrowth, synaptic plasticity, and apoptosis. However, the expression and function of Nck1 in the spinal cord and spinal cord injury remain unknown.Aims:To investigate the role of Nck1 in spinal cord injury.Study Design:Animal experimentation.Methods:Adult Sprague–Dawley rats were used to establish an acute spinal cord injury model. Double immunofluorescence staining, Western blot, and quantitative reverse transcription polymerase chain reaction analysis were used to investigate the distribution, cellular localization, and expression of Nck1 in spinal cord injury processes. Short interfering RNA was used to silence Nck1 expression in VSC4.1 cells. The Shapiro–Wilk test was used for the normality distribution analysis; the Student’s unpaired t-test, 1-way analysis of variance followed by post hoc Tukey’s test were used for data analysis. Finally, RNA sequencing technology and gene ontology analysis were used to analyze the changes in Nck1-associated genes expression after spinal cord injury.Results:Colabeled staining demonstrated that Nck1 was especially distributed in neurons. Western blot, quantitative reverse transcription polymerase chain reaction, and statistical analysis revealed that Nck1 expression reduced to the lowest levels at 1 day after nerve injury, and slowly increased to a stable level in 21 days (P < .05). Nck1-specific short interfering RNA transfection significantly reduced cell viability and neurite development in neurons. Bioinformatic analysis indicated that Nck1 participates in multiple pathological processes of spinal cord injury, and many Nck1-associated genes exhibited differential expression levels.Conclusion:Nck1 is a vital protein in spinal cord injury processes and, therefore, further studies should be conducted to explore its potential functions and molecular mechanisms in spinal cord injury repair.

Pharmacological Inhibition of Soluble Tumor Necrosis Factor-Alpha Two Weeks after High Thoracic Spinal Cord Injury Does Not Affect Sympathetic Hyperreflexia.

After a severe, high-level spinal cord injury (SCI), plasticity to intraspinal circuits below injury results in heightened spinal sympathetic reflex activity and detrimentally impacts peripheral organ systems. Such sympathetic hyperreflexia is immediately apparent as an episode of autonomic dysreflexia (AD), a life-threatening condition characterized by sudden hypertension and reflexive bradycardia following below-level sensory inputs; for example, pressure sores or impacted fecal matter. Over time, plasticity within the spinal sympathetic reflex (SSR) circuit contributes to the progressive intensification of AD events, as the frequency and severity of AD events increase greatly beginning ∼2 weeks post-injury (wpi). The neuroimmune system has been implicated in driving sympathetic hyperreflexia, as inhibition of the cytokine soluble tumor necrosis factor-alpha (sTNFα) using the biological mimetic XPro1595 beginning within days post-SCI has been shown to attenuate the development of AD. Here, we sought to further understand the effective therapeutic time window of XPro1595 to diminish sympathetic hyperreflexia, as indicated by AD. We delayed the commencement of continuous intrathecal administration of XPro1595 until 2 weeks after a complete, thoracic level 3 injury in adult rats. We examined the severity of colorectal distension-induced AD biweekly. We found that initiation of sTNFα inhibition at 2 wpi does not attenuate the severity or intensification of sympathetic hyperreflexia compared with saline-treated controls. Coupled with previous data from our group, these findings suggest that central sTNFα signaling must be targeted prior to 2 weeks post-SCI in order to decrease sympathetic hyperreflexia.

The influence of renal ischemia-reperfusion injury on remote organs: The histological brain changes in male and female rats.

INTRODUCTION:Brain tissue was adversely affected by renal ischemia-reperfusion injury (renal IRI) in several studies. Moreover, we are awareness that kidney diseases are gender dependent, but there is not enough evidence of the impact of gender on renal IRI-induced brain injury. Hence, this study was designed to investigate gender differences in renal IRI-induced brain tissue injury in adult rats.MATERIALS AND METHODS:Forty Wistar rats (four groups) include two main groups (20 male and 20 female). Each of them was divided into two subgroups including 1 and 2: male and female sham-operated groups and 3and 4: male and female ischemia (ISC) groups were exposed to renal ischemia for 45 min and then 24 h reperfusion (male and female ISC 24 h). Sham groups were exposed to surgery without ischemia process. After reperfusion time, blood samples were obtained for the renal function measurements. The kidney and brain were removed and were fixed in a 10% formalin solution for pathological assessment. The left kidney was used to measure malondialdehyde (MDA) and nitrite.RESULTS:Renal IRI increased significantly levels of creatinine, blood urea nitrogen, kidney weight, and damage score in both genders (P < 0.05). Furthermore, brain injuries were significantly higher following 24 h of reperfusion in male and female groups. Serum nitrite level and MDA concentration of female rats decreased significantly in ISC 24 h group (P < 0.05) but not in male rats.CONCLUSION:The brain tissue of both genders, male and female, is affected by renal IRI as a remote organ. Female sex hormones may indicate a protective role against IR by the nitric oxide pathway and antioxidant signaling.

Human Embryonic Stem Cell–derived Neural Crest Cells Promote Sprouting and Motor Recovery Following Spinal Cord Injury in Adult Rats

Spinal cord injury results in irreversible tissue damage and permanent sensorimotor impairment. The development of novel therapeutic strategies that improve the life quality of affected individuals is therefore of paramount importance. Cell transplantation is a promising approach for spinal cord injury treatment and the present study assesses the efficacy of human embryonic stem cell–derived neural crest cells as preclinical cell-based therapy candidates. The differentiated neural crest cells exhibited characteristic molecular signatures and produced a range of biologically active trophic factors that stimulated in vitro neurite outgrowth of rat primary dorsal root ganglia neurons. Transplantation of the neural crest cells into both acute and chronic rat cervical spinal cord injury models promoted remodeling of descending raphespinal projections and contributed to the partial recovery of forelimb motor function. The results achieved in this proof-of-concept study demonstrates that human embryonic stem cell–derived neural crest cells warrant further investigation as cell-based therapy candidates for the treatment of spinal cord injury.

Cytotoxic effect of cipó-pucá (Cissus sicyoides L.) supercritical extract on human red blood cells and as anti-inflammatory in spinal cord injury in adult rats

Cissus sicyoides L. is a plant that has great anti-inflammatory activity, due to the presence of phenolic compounds. The objective of this work was to identify such substances by HPLC and to evaluate the cytotoxic effect on human red blood cells, of the C. sicyoides extract obtained by supercritical extraction, using CO2 and EtOH as co-solvent, in comparison to the extract obtained by conventional extraction (Soxhlet), as well as, to evaluate its anti-inflammatory effect on spinal cord injury (SCI) in adult rats. In HPLC analysis, the UV/Visible spectral data revealed compounds with absorption bands in wavelengths characteristic of glycosylated flavonoids. The supercritical extract did not show cytotoxic effect, as there was no rupture of red blood cell membranes. The in vivo test demonstrated reduction in cell concentration in the lesion surrounding area in treated animals, suggesting an anti-inflammatory effect of the supercritical extract on the SCI model.

Combination treatments with therapeutic hypothermia for hypoxic‐ischemic neuroprotection

Therapeutic hypothermia is now proven to reduce death or disability in term and near-term born infants with moderate to severe hypoxic-ischemic encephalopathy. Nevertheless, many infants still survive with disability, despite treatment with hypothermia. Recent preclinical and clinical studies suggest that current protocols for therapeutic hypothermia are near-optimal. The obvious strategy, in addition to improving early initiation of therapeutic hypothermia after birth, is to combine hypothermia with other neuroprotective agents. We review evidence that the mechanisms of action of many promising agents overlap with the anti-excitotoxic, anti-apoptotic, and anti-inflammatory mechanisms of hypothermia, leading to a lack of benefit from combination treatment. Moreover, even apparently beneficial combinations have failed to translate in clinical trials. These considerations highlight the need for preclinical studies to test clinically realistic protocols of timing and duration of treatment, before committing to large randomized controlled trials.

Protective effects of royal jelly on testicular torsion induced ischaemia reperfusion injury in rats.

This study was performed to investigate the protective effects of royal jelly (RJ) on a testicular torsion-induced ischaemia/reperfusion (I/R) injury in adult rats. A total of 40 male Wistar rats were divided into four groups, including 10 rats in each group: Group 1 (sham), Group 2 (Control), group 3 (I/R rats treated with 100mg/kg RJ for 50days after torsion) and group 4( I/R rats treated with 20mg/kg vitamin C for 50days after torsion). Testicular torsion was created by rotating the right testes 720° a clockwise direction for 90min. The levels of testosterone were measured by ELISA. Pathological evaluation, mean maturity and quality of the seminiferous tubules were used. Results showed that the testicular histopathology standards and testosterone levels changes were statistically significant in groups 3 and 4. The results obtained in this study may suggest that RJ like vitamin C had protective effects on a testicular ischaemia/reperfusion-induced injury in rats.