scholarly journals Prenatal and Postnatal Methyl-Modulator Intervention Corrects the Stress-Induced Glucocorticoid Response in Low-Birthweight Rats

2021 ◽  
Vol 22 (18) ◽  
pp. 9767
Author(s):  
Takahiro Nemoto ◽  
Yoshihiko Kakinuma
Keyword(s):  
Restraint Stress ◽  
Feedback Loop ◽  
Metabolic Disorders ◽  
Glucocorticoid Receptors ◽  
Low Birthweight ◽  
Time Window ◽  
Stress Exposure ◽  
Glucocorticoid Response ◽  
As Stress ◽  
Therapeutic Time Window

Low body weight at birth has been shown to be a risk factor for future metabolic disorders, as well as stress response abnormalities and depression. We showed that low-birthweight rats had prolonged high blood corticosterone levels after stress exposure, and that an increase in Gas5 lncRNA, a decoy receptor for glucocorticoid receptors (GRs), reduces glucocorticoid responsiveness. Thus, we concluded that dampened pituitary glucocorticoid responsiveness disturbed the glucocorticoid feedback loop in low-birthweight rats. However, it remains unclear whether such glucocorticoid responsiveness is suppressed solely in the pituitary or systemically. The expression of Gas5 lncRNA increased only in the pituitary, and the intact induction of expression of the GR co-chaperone factor Fkbp5 against dexamethasone was seen in the liver, muscle, and adipose tissue. Intervention with a methyl-modulator diet (folate, VB12, choline, betaine, and zinc) immediately before or one week after delivery reversed the expression level of Gas5 lncRNA in the pituitary of the offspring. Consequently, it partially normalized the blood corticosterone levels after restraint stress exposure. In conclusion, the mode of glucocorticoid response in low-birthweight rats is impaired solely in the pituitary, and intervention with methyl-modulators ameliorates the impairment, but with a narrow therapeutic time window.

scholarly journals Chronic restraint stress impairs cognition via modulating HDAC2 expression

2021 ◽  
Vol 12 (1) ◽  
pp. 154-163
Author(s):  
Jie Wu ◽  
Cui Liu ◽  
Ling Zhang ◽  
Bing He ◽  
Wei-Ping Shi ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Hippocampal Neurons ◽  
Restraint Stress ◽  
Glucocorticoid Receptors ◽  
Chronic Restraint Stress ◽  
Akt Signaling Pathway ◽  
Object Recognition Test ◽  
Protein Levels ◽  
Synaptic Functions ◽  
Plus Maze

Abstract Background To investigate the effects of chronic restraint stress on cognition and the probable molecular mechanism in mice. Methods In the current work, a restraining tube was used as a way to induce chronic stress in mice. The protein levels were determined with ELISA and western blot. A series of behavior tests, including the Morris water maze, elevated plus maze, open field test, and novel object recognition test, were also performed to examine the anxiety and the ability of learning and memory. Moreover, murine neuroblastoma N2a cells were used to confirm the findings from mice under chronic stress. Results Decreased synaptic functions were impaired in chronic stress with the downregulation of PSD95, GluR-1, the neurotrophic factor BDNF, and immediate-onset genes Arc and Egr. Chronic restraint decreased the histone acetylation level in hippocampal neurons while HDAC2 was increased and was co-localized with glucocorticoid receptors. Moreover, chronic stress inhibited the PI3K/AKT signaling pathway and induced energy metabolism dysfunctions. Conclusion This work examining the elevated levels of HDAC2 in the hippocampus may provide new insights and targets for drug development for treating many neurodegenerative diseases.

Current Perspectives Regarding Stem Cell-based Therapy for Ischemic Stroke

2018 ◽  
Vol 24 (28) ◽  
pp. 3332-3340 ◽  
Author(s):  
Kyeong-Ah Kwak ◽  
Ho-Beom Kwon ◽  
Joo Won Lee ◽  
Young-Seok Park
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Time Window ◽  
Experimental Studies ◽  
Cell Type ◽  
Stroke Treatment ◽  
Cell Based Therapy ◽  
Regenerative Approach ◽  
Therapeutic Time Window

Stroke is a leading cause of death and disability worldwide. Conventional treatment has a limitation of very narrow therapeutic time window and its devastating nature necessitate a novel regenerative approach. Transplanted stem cells resulted in functional recovery through multiple mechanisms including neuroprotection, neurogenesis, angiogenesis, immunomodulation, and anti-inflammatory effects. Despite the promising features shown in experimental studies, results from clinical trials are inconclusive from the perspective of efficacy. The present review presents a synopsis of stem cell research on ischemic stroke treatment according to cell type. Clinical trials to the present are briefly summarized. Finally, the hurdles and issues to be solved are discussed for clinical application.

The yield of expanding the therapeutic time window for tPA

2006 ◽  
Vol 114 (5) ◽  
pp. 354-357 ◽  
Author(s):  
J. F. Owe ◽  
P. S. Sanaker ◽  
H. Næss ◽  
L. Thomassen
Keyword(s):  
Time Window ◽  
Therapeutic Time Window

scholarly journals Repeated restraint stress exposure during early withdrawal accelerates incubation of cue-induced cocaine craving

2016 ◽  
Vol 23 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Ryan M. Glynn ◽  
J. Amiel Rosenkranz ◽  
Marina E. Wolf ◽  
Aaron Caccamise ◽  
Freya Shroff ◽  
...  
Keyword(s):  
Restraint Stress ◽  
Stress Exposure ◽  
Early Withdrawal ◽  
Repeated Restraint Stress ◽  
Cocaine Craving

Review of clinical trials of neuroprotection in acute spinal cord injury

1999 ◽  
Vol 6 (1) ◽  
pp. E10 ◽  
Author(s):  
Charles H. Tator ◽  
Michael G. Fehlings
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Treatment Time ◽  
Time Window ◽  
Current Knowledge ◽  
Acute Spinal Cord Injury ◽  
Randomized Controlled Studies ◽  
Cord Injury ◽  
Therapeutic Time Window

In this paper the authors review the clinical trials of neuroprotection that have been performed for the treatment of acute spinal cord injury (SCI). The biological rationale for the selection of each treatment modality is discussed with reference to current knowledge of the principles in the management of acute SCI as well as the primary and secondary injury mechanisms identified by experimental and clinical studies of the pathophysiology of acute SCI. The trials are evaluated with regard to the availability and use of accurate clinical outcome measures, and the methodologies of the trials are critically evaluated with an emphasis on prospective randomized controlled studies. A detailed description and critical analysis are provided of the results of the 10 clinical trials conducted to date in which a randomized prospective controlled design has been used. The issue of the therapeutic time window in acute SCI is discussed. To date, methylprednisolone is the only effective neuroprotective agent that has been established for use in human SCI, and the only therapeutic time window established in human SCI is a maximum trauma-to-treatment time of 8 hours.

Therapeutic time window of rt-PA on embolic stroke in rat

2003 ◽  
Vol 1252 ◽  
pp. 203-207 ◽  
Author(s):  
Seiji Okubo ◽  
Hironaka Igarashi ◽  
Hiroshi Yamaguchi ◽  
Kazumasa Arii ◽  
Masanori Sakamaki ◽  
...  
Keyword(s):  
Time Window ◽  
Embolic Stroke ◽  
Therapeutic Time Window

Abstract T P10: Therapeutic Time Window for Endovascular Therapy of Acute Ischemic Stroke Depends on THRIVE Score: A Retrospective Single-center Study

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Kenichi Todo ◽  
Nobuyuki Sakai ◽  
Tomoyuki Kono ◽  
Taku Hoshi ◽  
Hirotoshi Imamura ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Endovascular Therapy ◽  
Time Window ◽  
Medical Center ◽  
Multivariate Logistic Regression Analysis ◽  
Symptom Duration ◽  
Vascular Events ◽  
Good Outcome ◽  
Therapeutic Time Window

Background and purpose: The outcome after endovascular therapy in acute ischemic stroke is associated with onset-to-reperfusion time (ORT). The Totaled Health Risks in Vascular Events (THRIVE) score is also an important pre-thrapeutic predictor of outcome. We hypothesized that the therapeutic time window is narrower in patients with the higher THRIVE score. Methods: We retrospectively studied consecutive 109 ischemic stroke patients with successful reperfusion after endovascular therapy between October 2005 and March 2014 at a single institute (Kobe City Medical Center General Hospital). Inclusion criteria was as follows: National Institutes of Health Stroke Scale (NIHSS) score ≥8, stroke symptom duration ≤8 h, premorbid modified Rankin Scale (mRS) score ≤2, and thrombolysis myocardial infarction score 2-3. We analyzed the relationships of ORT, THRIVE score, and THRIVE+ORT score with good outcome (mRS ≤2 at 3 months). The THRIVE+ORT score was defined as the sum of the THRIVE score and ORT (h). Results: Median ORT was 5.5 h (IQR; 4.4-7.1 h), median THRIVE score was 5 (IQR; 4-6), and median THRIVE+ORT score was 10.8 (IQR; 9.2-12.5). Good outcome rates for patients with ORT ≤4 h, >4 and ≤6 h, >6 and ≤8 h, and >8h were 50.0%, 45.8%, 37.0%, and 21.4%, respectively (p=0.3), those with THRIVE score ≤3, >3 and ≤5, >5 and ≤7, and >7 were 57.1%, 51.4%, 28.3%, and 20.0%, respectively (p9 and ≤11, >11 and ≤13, and >13 were 64.0%, 44.1%, 34.4%, and 16.7%, respectively (p<0.05). Multivariate logistic regression analysis revealed that THRIVE+ORT score was an independent predictor of good outcome after adjusted for THRIVE score (odds ratio [OR], 1.367; 95% confidence interval [CI], 1.082-1.728) or after adjusted for ORT (OR, 1.517: 95% CI, 1.160-1.983). Conclusion: Our study showed that THRIVE+ORT score was associated with outcome that was independent from THRIVE score or ORT. This is the first report to suggest that patients with the higher THRIVE score require the shorter ORT for good outcome.

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