scholarly journals Src Family Kinases Inhibition Ameliorates Hypoxic-Ischemic Brain Injury in Immature Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Han Qiu ◽  
Tianyang Qian ◽  
Tong Wu ◽  
Ting Gao ◽  
Qinghe Xing ◽  
...  
Keyword(s):  
Brain Injury ◽  
Western Blotting ◽  
Tissue Injury ◽  
Src Family Kinases ◽  
Morris Water Maze Test ◽  
Behavioral Tests ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Immature Rats ◽  
Nmdar Subunit

Hypoxic-ischemic (HI) injury is one of the initial factors contributing to neonatal brain injury. Src family kinases (SFKs) are considered to act as molecular hubs for N-methyl-d-aspartate receptor (NMDAR) regulation and participate in the HI injury process. The objectives of this study were to evaluate the levels of phospho-Src (p-Src), the relationship between NMDARs and SFKs, and the effects of SFK inhibition on an immature rat HI brain injury model. The model was induced in 3-day-old Sprague–Dawley rats using the Rice-Vannucci model operation. The level of p-Src was evaluated using Western blotting. The association of NMDARs with SFKs was detected using Western blotting and coimmunoprecipitation. After intraperitoneal injection of 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3,4-d] pyrimidine (PP2), an SFK-selective inhibitor, neuropathological changes were observed by performing H&E and immunofluorescence staining, and the neurological functions were assessed using the following behavioral tests: modified neurological severity score, open field test, and Morris water maze test. The levels of p-Src first decreased at 0 h after injury, increased at 2 h after injury, and continuously decreased from 6 h to 3 days. Along with the increased p-Src levels observed at 2 h after injury, the phosphorylation of NMDAR subunit NR2B at tyrosine 1472 was increased. Following the administration of PP2, the increased p-Src and NMDAR-2B levels detected at 2 h after injury were decreased, and tissue injury and myelin basic protein expression were improved at 7 days after injury. The PP2 intervention improved the performance of injured rats on behavioral tests. In conclusion, we determined the patterns of p-Src expression after HI brain injury in immature rats and showed a relationship with the activated NMDA receptor. The inhibition of p-Src ameliorates neuropathological changes and damages neurological functions induced by HI injury.

Curcumin Reduces Neuroinflammation and Improves the Impairments of Anesthetics on Learning and Memory by Regulating the Expression of miR-181a-5p

2021 ◽  
pp. 1-9
Author(s):  
Guizhen Liu ◽  
Yuchuan Sun ◽  
Fei Liu
Keyword(s):  
Cognitive Impairment ◽  
Protective Effect ◽  
Learning And Memory ◽  
Cognitive Dysfunction ◽  
Inflammatory Cytokines ◽  
Neuroprotective Effect ◽  
Morris Water Maze Test ◽  
Sprague Dawley ◽  
Protein Levels ◽  
Sprague Dawley Rats

<b><i>Objective:</i></b> The purpose of this study was to explore the role of curcumin (Cur) in isoflurane (ISO)-induced learning and memory dysfunction in Sprague-Dawley rats and further elucidate the mechanism of the protective effect produced by Cur. <b><i>Methods:</i></b> Rat models of cognitive impairment were established by inhaling 3% ISO. The Morris water maze test was used to assess the cognitive function of rats. ELISA and qRT-PCR were used to analyze the protein levels of pro-inflammatory cytokines and expression levels of miR-181a-5p, respectively. <b><i>Results:</i></b> Cur significantly improved the ISO-induced cognitive dysfunction in rats and alleviated the ISO-induced neuroinflammation. miR-181a-5p was overexpressed in ISO-induced rats, while Cur treatment significantly reduced the expression of miR-181a-5p. Overexpression of miR-181a-5p promoted the cognitive impairment and the release of inflammatory cytokines and reversed the neuroprotective effect of Cur. <b><i>Conclusion:</i></b> Cur has a protective effect on ISO-induced cognitive dysfunction, which may be achieved by regulating the expression of miR-181a-5p.

scholarly journals Pain Markers and Epidural Fibrosis Caused by Repeated Spinal Surgery in Sprague–Dawley Rats

2020 ◽  
Author(s):  
Meiling Quan ◽  
Jae-Hoon Kim ◽  
Won-Ha Hwang ◽  
Young-Yul KIM
Keyword(s):  
Western Blotting ◽  
Spinal Surgery ◽  
Immunohistochemical Analysis ◽  
Epidural Fibrosis ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Mitogen Activated Protein ◽  
Repeated Surgery ◽  
Group A ◽  
Group B

Abstract Background Epidural fibrosis is one of the aetiologies of pain following spinal revision surgery. However, roles of epidural fibrosis caused by repeated spinal surgery and pain-related proteins in causing the post spinal surgery syndrome remain unknown. In this study, using a rat spinal surgery epidural fibrosis and adhesion model, we evaluate and investigated the relationship between pain marker and epidural fibrosis caused by repeated spinal surgery in Sprague-Dawley rats. Methods Sprague–Dawley rats that underwent repeated spinal surgery were divided into three groups: group A (single laminectomy), group B (two repeated surgeries) and group C (three repeated surgeries). Dural thickness was measured in each experimental group, and immunohistochemical analysis and western blotting of mitogen-activated protein kinases were performed (ERK, p38 and JNK). Results Dural thickness was 6.363 ± 1.911 µm in group A, 13.238 ± 2.123 µm in group B and 19.4 ± 2.115 µm in group C. In western blotting, phosphorylated ERK expression was higher in groups B (1.77 fold) and C (2.42 fold) than in group A. Phosphorylated p38 expression was higher in groups B (1.17 fold) and C (1.33 fold) than in group A. Immunohistochemical analysis revealed that phosphorylated ERK and p38 expression gradually increased with the number of repeated surgeries, as evidenced by western blotting. Conclusions Repeated spinal surgery may increase dural thickness and expression of phosphorylated ERK and p38 in the spinal dorsal horn, suggesting that pain increases with repeated surgery.

THE INFLUENCE OF TUMOR GROWTH ON THE SYNTHESIS OF α2-AP (ACUTE PHASE) GLOBULIN OF RAT SERUM

1967 ◽  
Vol 45 (12) ◽  
pp. 1937-1941 ◽  
Author(s):  
Henry E. Weimer ◽  
Constance Humelbaugh ◽  
Dorothy M. Roberts
Keyword(s):  
Tumor Growth ◽  
Acute Phase ◽  
Tissue Injury ◽  
Sprague Dawley ◽  
Rat Serum ◽  
Serum Haptoglobin ◽  
Sprague Dawley Rats ◽  
Walker 256 ◽  
Implantation Procedure

The effects of growth of the Walker 256 carcinosarcoma on the α2-AP (acute phase) globulin, fibrinogen, seromucoid, and haptoglobin fractions of plasma were investigated in adult, male Sprague–Dawley rats in a longitudinal study. Early increases in α2-AP globulin and seromucoid levels were found to be related to the tissue injury associated with the implantation procedure. Significant elevations in the α2-AP globulin, fibrinogen, and seromucoid fractions coincided with the onset of progressive tumor growth. Serum haptoglobin concentrations exhibited a delayed rise. This was attributed to the in vivo formation of haptoglobin–hemoglobin complexes. It was suggested that the increases in all fractions reflected the release of humoral mediators from injured or necrotic cells wrhich stimulated increased synthesis of the fractions by the liver.

scholarly journals Influence of Therapeutic Hypothermia on Matrix Metalloproteinase Activity after Traumatic Brain Injury in Rats

2005 ◽  
Vol 25 (11) ◽  
pp. 1505-1516 ◽  
Author(s):  
Jessie S Truettner ◽  
Ofelia F Alonso ◽  
W Dalton Dietrich
Keyword(s):  
Brain Injury ◽  
Therapeutic Hypothermia ◽  
Brain Injuries ◽  
Brain Temperature ◽  
Sprague Dawley ◽  
Beneficial Effects ◽  
Sprague Dawley Rats ◽  
In Situ Zymography ◽  
Metalloproteinase Activity

Recent evidence suggests that matrix metalloproteinases (MMPs) contribute to acute edema and lesion formation following ischemic and traumatic brain injuries (TBI). Experimental and clinical studies have also reported the beneficial effects of posttraumatic hypothermia on histopathological and behavioral outcome. The purpose of this study was to determine whether therapeutic hypothermia would affect the activity of MMPs after TBI. Male Sprague-Dawley rats were traumatized by moderate parasagittal fluid-percussion (F-P) brain injury. Seven groups ( n = 5/group) of animals were investigated: sham-operated, TBI with normothermia (37°C), and TBI with hypothermia (33°C). Normothermia animals were killed at 4, 24, 72 h and 5 days, and hypothermia animals at 24 or 72 h. Brain temperature was reduced to target temperature 30 mins after trauma and maintained for 4 h. Ipsilateral and contralateral cortical, hippocampal, and thalamic regions were analyzed by gelatin and in situ zymography. In traumatized normothermic animals, TBI significantly ( P<0.005) increased MMP-9 levels in ipsilateral (right) cortical and hippocampal regions, compared with contralateral or sham animals, beginning at 4 h and persisting to 5 days. At 1, 3, and 5 days after TBI, significant increases in MMP-2 levels were observed. In contrast to these findings observed with normothermia, posttraumatic hypothermia significantly reduced MMP-9 levels. Hypothermic treatment, however, did not affect the delayed activation of MMP-2. Clarifying the mechanisms underlying the beneficial effects of posttraumatic hypothermia is an active area of research. Posttraumatic hypothermia may attenuate the deleterious consequences of brain trauma by reducing MMP activation acutely.

scholarly journals Ventilatory responses to ozone are reduced in immature rats

2000 ◽  
Vol 88 (6) ◽  
pp. 2023-2030 ◽  
Author(s):  
S. A. Shore ◽  
J. H. Abraham ◽  
I. N. Schwartzman ◽  
G. G. Krishna Murthy ◽  
J. D. Laporte
Keyword(s):  
Bronchoalveolar Lavage ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Ventilatory Responses ◽  
Sprague Dawley Rats ◽  
Immature Rats ◽  
Old Rats ◽  
Induced Changes

During ozone (O3) exposure, adult rats decrease their minute ventilation (V˙e). To determine whether such changes are also observed in immature animals, Sprague-Dawley rats, aged 2, 4, 6, 8, or 12 wk, were exposed to O3(2 ppm) in nose-only-exposure plethysmographs. BaselineV˙e normalized for body weight decreased with age from 2.1 ± 0.1 ml ⋅ min−1⋅ g−1in 2-wk-old rats to 0.72 ± 0.03 ml ⋅ min−1⋅ g−1in 12-wk-old rats, consistent with the higher metabolic rates of younger animals. In adult (8- and 12-wk-old) rats, O3caused 40–50% decreases in V˙e that occurred primarily as the result of a decrease in tidal volume. In 6-wk-old rats, O3-induced changes inV˙e were significantly less, and in 2- and 4-wk-old rats, no significant changes inV˙e were observed during O3exposure. The increased baseline V˙e and the smaller decrements in V˙e induced by O3in the immature rats imply that their delivered dose of O3is much higher than in adult rats. To determine whether these differences in O3dose influence the extent of injury, we measured bronchoalveolar lavage protein concentrations. The magnitude of the changes in bronchoalveolar lavage induced by O3was significantly greater in 2- than in 8-wk-old rats (267 ± 47 vs. 165 ± 22%, respectively, P < 0.05). O3exposure also caused a significant increase in PGE2in 2-wk-old but not in adult rats. The results indicate that the ventilatory response to O3is absent in 2-wk-old rats and that lack of this response, in conjunction with a greater specific ventilation, leads to greater lung injury.

scholarly journals Ghrelin Prevents Cisplatin-Induced Mechanical Hyperalgesia and Cachexia

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 455-460 ◽  
Author(s):  
José M. Garcia ◽  
Juan P. Cata ◽  
Patrick M. Dougherty ◽  
Roy G. Smith
Keyword(s):  
Quality Of Life ◽  
Chemotherapeutic Agent ◽  
Thermal Sensitivity ◽  
Mechanical Hyperalgesia ◽  
Behavioral Tests ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Unique Model ◽  
Igf I

Complications induced by the chemotherapeutic agent cisplatin, such as neuropathy and cachexia, occur frequently, are often dose limiting, and have an impact on quality of life and survival in cancer patients. The recently discovered hormone ghrelin is a potent GH secretagogue with orexigenic and neuroprotective properties that may prevent or ameliorate these complications. The objective of this study was to determine the effects of ghrelin administration on mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Adult male Sprague-Dawley rats were given cisplatin, ghrelin, ghrelin-cisplatin, or vehicle ip. Food intake and body weight were measured daily. Behavioral tests to assess the development of hyperalgesia were conducted by measuring mechanical and thermal sensitivity. Plasma ghrelin and IGF-I levels were also measured. Our results indicate that ghrelin coadministration inhibited the development of cisplatin-induced mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Although ghrelin treatment had no effect on plasma IGF-I levels in control rats, it prevented the decrease in IGF-I levels induced by cisplatin. The attenuation of cisplatin-induced mechanical hyperalgesia induced by ghrelin was correlated with the prevention of cisplatin-induced lowering of IGF-I. In conclusion, ghrelin administration may be useful in the treatment or prevention of chemotherapy induced neuropathy and cachexia. Attenuation of mechanical hyperalgesia in the rat by the hormone ghrelin provides a unique model for elucidating the mechanisms involved, which are essential toward our understanding of these complications.

scholarly journals Posttraumatic therapeutic hypothermia alters microglial and macrophage polarization toward a beneficial phenotype

2016 ◽  
Vol 37 (8) ◽  
pp. 2952-2962 ◽  
Author(s):  
Jessie S Truettner ◽  
Helen M Bramlett ◽  
W Dalton Dietrich
Keyword(s):  
Brain Injury ◽  
Therapeutic Hypothermia ◽  
Macrophage Polarization ◽  
Temperature Sensitive ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
M2 Microglia ◽  
Sprague Dawley Rats ◽  
Inflammatory Processes ◽  
Clinical Models

Posttraumatic inflammatory processes contribute to pathological and reparative processes observed after traumatic brain injury (TBI). Recent findings have emphasized that these divergent effects result from subsets of proinflammatory (M1) or anti-inflammatory (M2) microglia and macrophages. Therapeutic hypothermia has been tested in preclinical and clinical models of TBI to limit secondary injury mechanisms including proinflammatory processes. This study evaluated the effects of posttraumatic hypothermia (PTH) on phenotype patterns of microglia/macrophages. Sprague-Dawley rats underwent moderate fluid percussion brain injury with normothermia (37℃) or hypothermia (33℃). Cortical and hippocampal regions were analyzed using flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR) at several periods after injury. Compared to normothermia, PTH attenuated infiltrating cortical macrophages positive for CD11b+ and CD45high. At 24 h, the ratio of iNOS+ (M1) to arginase+ (M2) cells after hypothermia showed a decrease compared to normothermia. RT-PCR of M1-associated genes including iNOS and IL-1β was significantly reduced with hypothermia while M2-associated genes including arginase and CD163 were significantly increased compared to normothermic conditions. The injury-induced increased expression of the chemokine Ccl2 was also reduced with PTH. These studies provide a link between temperature-sensitive alterations in macrophage/microglia activation and polarization toward a M2 phenotype that could be permissive for cell survival and repair.

scholarly journals Pre-existing hypertension and pregnancy induced hypertension reveal molecular differences in placental proteome in rodents

2021 ◽  
Author(s):  
Sheon Mary ◽  
Heather Small ◽  
Florian Herse ◽  
Emma Carrick ◽  
Arun Flynn ◽  
...  
Keyword(s):  
Gestational Hypertension ◽  
Tissue Injury ◽  
Cardiovascular Complications ◽  
Trophoblast Invasion ◽  
Future Research ◽  
Chronic Hypertension ◽  
Label Free ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Sprague Dawley Rats

Pre-existing or new onset of hypertension affects pregnancy and is one of the leading causes of maternal and fetal morbidity and mortality. In certain cases, it also leads to long term maternal cardiovascular complications. The placenta is a key player in the pathogenesis of complicated hypertensive pregnancies, however the pathomechanisms leading to an abnormal placenta are poorly understood. In this study we compared the placental proteome of two rat models: a pre-existing hypertension pregnancy model (stroke-prone spontaneously hypertensive, SHRSP) and the transgenic RAS activated gestational hypertension model (transgenic for human angiotensinogen Sprague-Dawley rats, SD-PE). Label-free proteomics using nano LC-MS/MS was performed for identification and quantification of proteins. Between the two models, we found widespread differences in the expression of placental proteins including those related to hypertension, inflammation and trophoblast invasion; whereas pathways such as regulation of serine endopeptidase activity, tissue injury response, coagulation and complement activation were enriched in both models. We present for the first time the placental proteome of SHRSP and SD-PE and provide insight into the molecular make-up of models of hypertensive pregnancy. Our study informs future research into specific preeclampsia and chronic hypertension pregnancy mechanisms and translation of rodent data to the clinic.

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