scholarly journals Progesterone and its Metabolite Allopregnanolone Differentially Regulate Hemostatic Proteins after Traumatic Brain Injury

2008 ◽  
Vol 28 (11) ◽  
pp. 1786-1794 ◽  
Author(s):  
Jacob W VanLandingham ◽  
Milos Cekic ◽  
Sarah M Cutler ◽  
Stuart W Hoffman ◽  
Ebony R Washington ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Expression ◽  
Functional Outcomes ◽  
Coagulation Factor ◽  
Tissue Type ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Type Plasminogen Activator ◽  
Coagulation Protein

Our laboratory has shown in numerous experiments that the neurosteroids progesterone (PROG) and allopregnanolone (ALLO) improve molecular and functional outcomes after traumatic brain injury (TBI). As coagulopathy is an important contributor to the secondary destruction of nervous tissue, we hypothesized that PROG and ALLO administration may also have a beneficial effect on coagulation protein expression after TBI. Adult male Sprague—Dawley rats were given bilateral contusions of the medial frontal cortex followed by treatments with PROG (16 mg/kg), ALLO (8 mg/kg), or vehicle (22.5% hydroxypropyl-β-cyclodextrin). Controls received no injury or injections. Progesterone generally maintained procoagulant (thrombin, fibrinogen, and coagulation factor XIII), whereas ALLO increased anticoagulant protein expression (tissue-type plasminogen activator, tPA). In addition, PROG significantly increased the ratio of tPA bound to neuroserpin, a serine protease inhibitor that can reduce the activity of tPA. Our findings suggest that in a model of TBI, where blood loss may exacerbate injury, it may be preferable to treat patients with PROG, whereas it might be more appropriate to use ALLO as a treatment for thrombotic stroke, where a reduction in coagulation would be more beneficial.

Plasminogen activator inhibitor-1 rises after hemorrhage in rats

1995 ◽  
Vol 268 (6) ◽  
pp. E1065-E1069 ◽  
Author(s):  
M. Yamashita ◽  
D. N. Darlington ◽  
E. J. Weeks ◽  
R. O. Jones ◽  
D. S. Gann
Keyword(s):  
Plasminogen Activator ◽  
High Performance ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Sprague Dawley ◽  
Plasminogen Activator Inhibitor 1 ◽  
Sprague Dawley Rats ◽  
Type Plasminogen Activator ◽  
Activator Inhibitor ◽  
Pai 1

Large hemorrhage leads to hypercoagulability, a phenomenon that has never been well explained. Because an elevation of plasminogen activator inhibitor (PAI)-1 increases procoagulant activity, we have determined whether plasma PAI activity and tissue PAI-1 mRNA are elevated after hemorrhage. Sprague-Dawley rats were bled (20 or 15 ml/kg) 4 days after cannulation. Plasma PAI activity was determined by the capacity of plasma to inhibit tissue-type plasminogen activator activity. Changes of PAI-1 mRNA in various tissues were detected by high-performance liquid chromatography after reverse transcription and polymerase chain reaction. Hemorrhage (20 ml/kg) significantly elevated plasma PAI activity at 0.5, 1, 2, 4, 6, and 8 h after hemorrhage and PAI-1 mRNA in liver at 1, 2, 4, and 6 h after hemorrhage. The PAI-1 message was also significantly elevated in lung, heart, and kidney at 4 h after hemorrhage. The increases of PAI-1 mRNA after 20 ml/kg hemorrhage were significantly greater than those after 15 ml/kg hemorrhage. These findings indicate that large hemorrhage can induce the increases in PAI activity and PAI-1 message and suggest that induction of PAI-1 may be involved in the thrombogenic responses observed after large hemorrhage.

scholarly journals Effect of Polyarginine Peptide R18D Following a Traumatic Brain Injury in Sprague-Dawley Rats

2020 ◽  
Vol 92 ◽  
pp. 100584
Author(s):  
Li Shan Chiu ◽  
Ryan S. Anderton ◽  
Vince W. Clark ◽  
Jane L. Cross ◽  
Neville W. Knuckey ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Determining Sex-based Differences in Inflammatory Response in an Experimental Traumatic Brain Injury Model

2021 ◽  
Author(s):  
Michael Collins Scott ◽  
Karthik Prabhakara ◽  
Andrew J. Walters ◽  
Scott D. Olson ◽  
Charles S. Cox
Keyword(s):  
Traumatic Brain Injury ◽  
Flow Cytometry ◽  
Brain Injury ◽  
Rodent Model ◽  
Sprague Dawley ◽  
Male And Female ◽  
Cytokine Analysis ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Bbb Permeability

Abstract Introduction: Traumatic brain injury is a leading cause of injury-related death and morbidity. Despite multiple clinical and pre-clinical studies, sex-based differences in blunt TBI outcomes based remain unclear. Our accepted rodent model of blunt traumatic brain injury was used to identify differences in the pathological features of blunt TBI. Methods: Male and female Sprague-Dawley rats were subjected to either controlled-cortical impact (CCI) or sham injury; brain tissue was harvested at different time intervals depending on the specific study. Blood-brain barrier (BBB) analysis was performed using Alexa Fluor 680 dye. Microglia and splenocytes were characterized with traditional flow cytometry; microglia markers such as CD45, P2Y12, CD32, and CD163 were analyzed with t-distributed stochastic neighbor embedding (t-SNE). Flow cytometry was used to study tissue cytokine levels, and supplemented with ELISAs of TNF-⍺, IL-17, and IL-1β of the ipsilateral hemisphere tissue were performed. Results: CCI groups had an increase in BBB permeability in both sexes. There was significant difference in the integrated density value of BBB permeability between the male CCI group and the female CCI group (female CCI mean = 3.08 x 108 ± 2.83 x 107, male CCI mean = 2.20 x 108 ± 4.05 x 106, p = 0.0210), but otherwise no differences were observed. Traditional flow cytometry did not distinguish any sex-based difference in regards to splenocyte cell population after CCI. t-SNE did not reveal any significant difference between the male and female injury groups in the activation of microglia. Cytokine analysis after injury by flow cytometry and ELISA did not reveal any significant differences between sex. Conclusion: In our rodent model of blunt traumatic brain injury, sex-based differences in pathology and neuroinflammation are limited, and only noted in one specific analysis of BBB permeability.

scholarly journals Dynamics of clusterin protein expression in the brain and plasma following experimental traumatic brain injury

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shalini Das Gupta ◽  
Anssi Lipponen ◽  
Kaisa M. A. Paldanius ◽  
Noora Puhakka ◽  
Asla Pitkänen
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Expression ◽  
Fold Increase ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Post Injury ◽  
Fluid Percussion Injury ◽  
Clusterin Protein ◽  
The Brain

AbstractProgress in the preclinical and clinical development of neuroprotective and antiepileptogenic treatments for traumatic brain injury (TBI) necessitates the discovery of prognostic biomarkers for post-injury outcome. Our previous mRNA-seq data revealed a 1.8–2.5 fold increase in clusterin mRNA expression in lesioned brain areas in rats with lateral fluid-percussion injury (FPI)-induced TBI. On this basis, we hypothesized that TBI leads to increases in the brain levels of clusterin protein, and consequently, increased plasma clusterin levels. For evaluation, we induced TBI in adult male Sprague-Dawley rats (n = 80) by lateral FPI. We validated our mRNA-seq findings with RT-qPCR, confirming increased clusterin mRNA levels in the perilesional cortex (FC 3.3, p < 0.01) and ipsilateral thalamus (FC 2.4, p < 0.05) at 3 months post-TBI. Immunohistochemistry revealed a marked increase in extracellular clusterin protein expression in the perilesional cortex and ipsilateral hippocampus (7d to 1 month post-TBI), and ipsilateral thalamus (14d to 12 months post-TBI). In the thalamus, punctate immunoreactivity was most intense around activated microglia and mitochondria. Enzyme-linked immunoassays indicated that an acute 15% reduction, rather than an increase in plasma clusterin levels differentiated animals with TBI from sham-operated controls (AUC 0.851, p < 0.05). Our findings suggest that plasma clusterin is a candidate biomarker for acute TBI diagnosis.

scholarly journals Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jingchuan Wu ◽  
Hui Li ◽  
Junchi He ◽  
Xiaocui Tian ◽  
Shuilian Luo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurovascular Unit ◽  
Chronic Phase ◽  
Synaptic Proteins ◽  
Luciferase Reporter ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Brain Tissues

AbstractThe level of microRNA-9-5p (miRNA-9-5p) in brain tissues is significantly changed in the chronic phase after traumatic brain injury (TBI). However, the effect of miRNA-9-5p on brain function after TBI has not been elucidated. In this study, we used a controlled cortical impact (CCI) model to induce TBI in Sprague–Dawley rats. Brain microvascular endothelial cells (BMECs), astrocytes, and neurons were extracted from immature Sprague–Dawley rats and cocultured to reconstruct the neurovascular unit (NVU) in vitro. The results showed that downregulation of miRNA-9-5p in the chronic phase contributed to neurological function recovery by promoting astrocyte proliferation and increasing the release of astrocyte-derived neurotrophic factors around injured brain tissues after TBI. A dual-luciferase reporter assay validated that miRNA-9-5p was a post-transcriptional modulator of thrombospondin 2 (Thbs-2), and downregulation of miRNA-9-5p promoted Thbs-2 expression in astrocytes. Furthermore, we verified that Thbs-2 can promote Notch pathway activation by directly binding to Jagged and Notch. Through in vitro experiments, we found that the expression of synaptic proteins and the number of synaptic bodies were increased in neurons in the NVU, which was constructed using astrocytes pretreated with miRNA-9-5p inhibitor. Moreover, we also found that downregulation of miRNA-9-5p promoted Thbs-2 expression in astrocytes, which activated the Notch/cylindromatosis/transforming growth factor-β-activated kinase 1 pathway in neurons and promoted the expression of synaptic proteins, including post-synaptic density protein 95 and synaptotagmin. Based on these results, miRNA-9-5p may be a new promising prognostic marker and treatment target for TBI.

scholarly journals Strain Differences in Response to Traumatic Brain Injury in Long-Evans Compared to Sprague-Dawley Rats

2009 ◽  
Vol 26 (4) ◽  
pp. 539-548 ◽  
Author(s):  
Arlene A. Tan ◽  
Andrea Quigley ◽  
Douglas C. Smith ◽  
Michael R. Hoane
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Strain Differences ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Long Evans

scholarly journals EFFECT OF MANGOSTEEN EXTRACT ON NEUROINFLAMMATION IN RAT MODEL OF ACUTE TRAUMATIC BRAIN INJURY

2019 ◽  
pp. 61-63
Author(s):  
ANDRE MAROLOP PANGIHUTAN SIAHAAN ◽  
SARMA LUMBANRAJA
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Treatment Group ◽  
Closed Head Injury ◽  
Sprague Dawley ◽  
Secondary Insult ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Gfap Expression ◽  
Cd 68

Objective: Traumatic brain injury (TBI) is one of the major health problems regarding morbidity and mortality, especially in productive ages. Following primary injury, there is a secondary insult, resulting in oxidative stress, neuroinflammation, and cell death. Mangosteen is a powerful natural antioxidant and anti-inflammation that also has neuroprotective property. The aim of this study was to explore the effect of mangosteen extract (ME)on neuroinflammation following TBI. Methods: A total of 30 Sprague-Dawley rats were randomized into three treatments group, i.e., sham-operated controls, closed head injury (CHI), and treatment group. In the treatment group, we gave ME once daily every day after CHI for 7 days. As oxidative process marker, we investigated malondialdehyde (MDA) expression. As neuroinflammation marker, we investigated glial fibrillary acidic protein (GFAP) and CD-68. Results: TBI increased the expression of GFAP and CD-68, but not MDA. There was significant GFAP expression difference between treatment group and CHI group. Regarding the expression of CD-68 and MDA, there was no significant difference between treatment and CHI group. Conclusion: Mangosteen extract supplementation decreased GFAP expression significantly after TBI.

Differential early effects of traumatic brain injury on spike-wave discharges in Sprague-Dawley rats

2020 ◽  
Author(s):  
Ilia G. Komoltsev ◽  
Stepan O. Frankevich ◽  
Natalia I. Shirobokova ◽  
Aleksandra A. Volkova ◽  
Irina P. Levshina ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Spike Wave Discharges ◽  
Early Effects ◽  
Spike Wave
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