The effect of female sexual hormones on the intestinal and serum cytokine response after traumatic brain injury: different roles for estrogen receptor subtypes

2013 ◽  
Vol 91 (9) ◽  
pp. 700-707 ◽  
Author(s):  
Mohammad Khaksari ◽  
Zakieh Keshavarzi ◽  
Ahmad Gholamhoseinian ◽  
Bahram Bibak

The purpose of this study was to evaluate the effect of female sexual hormones on intestinal and serum cytokines following traumatic brain injury (TBI). Adult female rats were ovariectomized and distributed among the following 9 groups: (i) sham trauma, (ii) TBI (Marmarou’s method), (iii) vehicle (dimethylsulfoxide) treated, (iv) estrogen (E2) treated, (v) progesterone (P) treated, (vi) treated with E2+P, (vii) propylpyrazole triol (PPT) treated, (viii) diarylpropionitrile (DPN) treated, and (ix) control. PPT and DPN are estrogen receptor αand β agonists, respectively. Serum and intestinal levels of interleukin (IL)-1β were increased by TBI (P < 0.001). The level of intestinal IL-1β was increased in the group treated with E2 (P < 0.001). There was a reduction in serum IL-1β (P < 0.01) and an increase in intestinal IL-1β level (P < 0.001) in the PPT-treated group compared with the vehicle-treated group. TBI reduced serum IL-6 (P < 0.01) and increased intestinal IL-6 (P < 0.001). Serum IL-6 was increased in the group treated with E2 (P < 0.001), P (P < 0.001), E2+P (P < 0.01), and DPN (P < 0.001) after TBI; however, intestinal IL-6 was higher in the E2-treated group compared with the vehicle-treated group (P < 0.01). Intestinal tumor necrosis factor α (TNF-α) was increased by TBI (P < 0.001). Progesterone decreased serum TNF-α (P < 0.01). Intestinal TNF-α in the E2 (P < 0.01), E2+P (P < 0.001), and PPT (P < 0.001) treatment groups was less than in the vehicle-treated group. In conclusion, estrogen influences the intestinal levels of proinflammatory cytokines, in particular TNF-α, mediated through estrogen receptor α.

2020 ◽  
pp. 401-415
Author(s):  
Roshni D. Thakkar ◽  
Ruimin Wang ◽  
Gangadhara R. Sareddy ◽  
Ratna K. Vadlamudi ◽  
Darrell W. Brann

The steroid hormone 17β‎-estradiol (E2) is neuroprotective in several neurodegenerative conditions, including cerebral ischemia, traumatic brain injury, and Alzheimer’s disease (AD). This chapter focuses on the evidence supporting a neuroprotective role of E2 in the hippocampus in cerebral ischemia and AD and reviews various mechanisms thought to underlie E2-induced neuroprotection. Specifically, the chapter discusses the mechanistic role of (a) the various estrogen receptor subtypes, (b) genomic versus nongenomic signaling, (c) regulation of the prosurvival Wnt/β‎−catenin pathway, and (d) anti-inflammatory effects of E2 in the hippocampus. Finally, we also discuss the role of a novel estrogen receptor co-activator protein, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) in mediating E2 genomic and non-genomic signaling, as well as the neuroprotective and cognitive-enhancing effects of E2 in the hippocampus.


2009 ◽  
Vol 37 (12) ◽  
pp. 3097-3106 ◽  
Author(s):  
Sheng-Hsien Chen ◽  
Chia-Yu Chang ◽  
Hsiu-Kang Chang ◽  
Wei-Chun Chen ◽  
Mao-Tsun Lin ◽  
...  

2018 ◽  
Vol 112 ◽  
pp. e278-e287 ◽  
Author(s):  
Sher-Wei Lim ◽  
Eric Nyam TT ◽  
Cho-Ya Hu ◽  
Chung-Ching Chio ◽  
Che-Chuan Wang ◽  
...  

2019 ◽  
Vol 41 (3-4) ◽  
pp. 203-211 ◽  
Author(s):  
Yu-xiang Wang ◽  
Lin Zhu ◽  
Li-xia Li ◽  
Hui-nan Xu ◽  
Hong-gang Wang ◽  
...  

The Papez circuit is crucial for several brain functions, including long-term memory and emotion. Estradiol modulates cognitive functions based on the expression pattern of its receptor subtypes including estrogen receptor (ER) α, β, and G protein-coupled receptor 30 (GPR30). Similarly, the activity in the cholinergic system correlates with several brain functions, such as learning and memory. In this study, we used immunofluorescence to examine the expression patterns of ERβ and Western blotting to analyze GPR30 and choline acetyltransferase (ChAT) expression, in different regions of the Papez circuit, including the prefrontal cortex, hippocampus, hypothalamus, anterior nucleus of the thalamus, and cingulum in female rats at postnatal days (PND) 1, 10, and 56. Our main finding was that the highest expression of ERβ and GPR30 was noted in each brain area of the Papez circuit in the PND1 rats, whereas the expression of ChAT was the highest in PND10 rats. These results provide vital information on the postnatal expression patterns of ER subtypes and ChAT in different regions of the Papez circuit.


2020 ◽  
Vol 21 (21) ◽  
pp. 8256 ◽  
Author(s):  
Min Kyu Park ◽  
Bo Young Choi ◽  
A Ra Kho ◽  
Song Hee Lee ◽  
Dae Ki Hong ◽  
...  

Traumatic brain injury (TBI) can cause physical, cognitive, social, and behavioral changes that can lead to permanent disability or death. After primary brain injury, translocated free zinc can accumulate in neurons and lead to secondary events such as oxidative stress, inflammation, edema, swelling, and cognitive impairment. Under pathological conditions, such as ischemia and TBI, excessive zinc release, and accumulation occurs in neurons. Based on previous research, it hypothesized that calcium as well as zinc would be influx into the TRPC5 channel. Therefore, we hypothesized that the suppression of TRPC5 would prevent neuronal cell death by reducing the influx of zinc and calcium. To test our hypothesis, we used a TBI animal model. After the TBI, we immediately injected NU6027 (1 mg/kg, intraperitoneal), TRPC5 inhibitor, and then sacrificed animals 24 h later. We conducted Fluoro-Jade B (FJB) staining to confirm the presence of degenerating neurons in the hippocampal cornus ammonis 3 (CA3). After the TBI, the degenerating neuronal cell count was decreased in the NU6027-treated group compared with the vehicle-treated group. Our findings suggest that the suppression of TRPC5 can open a new therapeutic window for a reduction of the neuronal death that may occur after TBI.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
David K. Wright ◽  
Jamie N. Mayo ◽  
Mujun Sun ◽  
Terence J. O’Brien ◽  
Sandy R. Shultz

AbstractNeurovascular injury has been proposed as a universal pathological hallmark of traumatic brain injury (TBI) with molecular markers of angiogenesis and endothelial function associated with injury severity and morbidity. Sex differences in the neurovasculature response post-TBI may contribute to the differences seen in how males and females respond to injury. Steady-state contrast enhanced magnetic resonance imaging (SSCE-MRI) can be used to non-invasively assess the neurovasculature and may be a useful tool in understanding and predicting outcomes post-TBI. Here we used SSCE-MRI to investigate the neurovasculature of male and female rats at 48 h after an experimental TBI, and how these changes related to neuromotor function at 1-week post-TBI. In addition to TBI induced changes, we found that female rats had greater vessel density, greater cerebral blood volumes and performed better on a neuromotor task than their male counterparts. These results suggest that acute post-TBI cerebrovascular function is worse in males, and that this may contribute to the greater functional deficits observed post-injury. Furthermore, these results highlight the potential of SSCE-MRI to provide insights into the cerebral microvasculature post-TBI. Future studies, incorporating both males and females, are warranted to investigate the evolution of these changes and the underlying mechanisms.


2004 ◽  
Vol 75 (6) ◽  
pp. 1166-1172 ◽  
Author(s):  
K. Chad Lambert ◽  
Edward M. Curran ◽  
Barbara M. Judy ◽  
Dennis B. Lubahn ◽  
D. Mark Estes

2019 ◽  
Vol 13 ◽  
Author(s):  
Mojdeh Hajmohammadi ◽  
Mohammad Khaksari ◽  
Zahra Soltani ◽  
Nader Shahrokhi ◽  
Hamid Najafipour ◽  
...  

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