The role of estrogen and progesterone, administered alone and in combination, in modulating cytokine concentration following traumatic brain injury

2011 ◽  
Vol 89 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Mohammad Khaksari ◽  
Zahra Soltani ◽  
Nader Shahrokhi ◽  
Gholamreza Moshtaghi ◽  
Gholamreza Asadikaram
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Water Content ◽  
Treated Group ◽  
Inhibitory Effect ◽  
Ovariectomized Rats ◽  
Brain Level ◽  
The Brain ◽  
Brain Water

Cytokines play an important role in the pathophysiology of traumatic brain injury (TBI). This study was designed to determine the effects of administering progesterone (P) and estrogen (E), alone and in combination, on brain water content, blood–brain barrier (BBB) disturbance, and brain level of cytokines following diffuse TBI. Ovariectomized rats were divided into 9 groups, treated with vehicle, E1, E2, P1, P2, E1+P1, E1+P2, E2+P1, and E2+P2. Levels of BBB disruption (5 h), cytokines, and water content (24 h) were evaluated after TBI induced by the Marmarou method. Physiological (E1 and P1) and pharmacological (E2 and P2) doses of estrogen and progesterone were administered 30 min after TBI. Water content in the E1+P2-treated group was higher than in the E1-treated group. The inhibitory effect of E2 on water content was reduced by adding progesterone. The inhibitory effect of E1 and E2 on Evans blue content was reduced by treatment with E1+P1 and E2+P2, respectively. The brain level of IL-1β was reduced in E1 and E2, after TBI. In the E2+P2-treated group, this level was higher than in the E2-treated group. The brain level of TGF-β was also elevated by the administration of progesterone and estrogen alone, and reduced when the hormones were administered in combination. In conclusion, a combined administration of progesterone and estrogen inhibited the decreasing effects of administration of progesterone and estrogen alone on water content and BBB disruption that mediated to change the proinflammatory cytokines.

scholarly journals Ulinastatin alleviates traumatic brain injury by reducing endothelin-1

2020 ◽  
Vol 12 (1) ◽  
pp. 001-008
Author(s):  
Ting Liu ◽  
Xing-Zhi Liao ◽  
Mai-Tao Zhou
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Water Content ◽  
Brain Edema ◽  
Rat Model ◽  
Neurosurgical Procedures ◽  
Brain Water Content ◽  
The Brain ◽  
Brain Water

Abstract Background Brain edema is one of the major causes of fatality and disability associated with injury and neurosurgical procedures. The goal of this study was to evaluate the effect of ulinastatin (UTI), a protease inhibitor, on astrocytes in a rat model of traumatic brain injury (TBI). Methodology A rat model of TBI was established. Animals were randomly divided into 2 groups – one group was treated with normal saline and the second group was treated with UTI (50,000 U/kg). The brain water content and permeability of the blood–brain barrier were assessed in the two groups along with a sham group (no TBI). Expression of the glial fibrillary acidic protein, endthelin-1 (ET-1), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry and western blot. Effect of UTI on ERK and PI3K/AKT signaling pathways was measured by western blot. Results UTI significantly decreased the brain water content and extravasation of the Evans blue dye. This attenuation was associated with decreased activation of the astrocytes and ET-1. UTI treatment decreased ERK and Akt activation and inhibited the expression of pro-inflammatory VEGF and MMP-9. Conclusion UTI can alleviate brain edema resulting from TBI by inhibiting astrocyte activation and ET-1 production.

Contribution of estrogen receptors alpha and beta in the brain response to traumatic brain injury

2013 ◽  
Vol 119 (2) ◽  
pp. 353-361 ◽  
Author(s):  
Saleh Zahedi Asl ◽  
Mohammad Khaksari ◽  
Ali Siahposht Khachki ◽  
Nader Shahrokhi ◽  
Shahla Nourizade
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Water Content ◽  
Female Rats ◽  
Blue Dye ◽  
Brain Water Content ◽  
Neuroprotective Effects ◽  
Selective Agonist ◽  
The Brain ◽  
Brain Water

Object Although there is evidence that estradiol has neuroprotective effects after traumatic brain injury (TBI) in female rats, it is unclear which estrogen receptor (ER) subtype, ERα or ERβ, mediates this effect. The authors therefore examined the roles of the different ERs in this effect. Here the authors used the ERα selective agonist propyl pyrazole triol (PPT) and the ERβ selective agonist diarylpropionitrile (DPN) alone and in combination in female rats to investigate this question. Methods Before the ovariectomized animals were injured using the Marmarou TBI technique, they were randomly divided into the following 9 groups: control, sham, TBI, vehicle, E1 (physiological dose of 17-β estradiol), E2 (pharmacological dose of 17-β estradiol), PPT, DPN, and PPT+DPN. Levels of blood-brain barrier (BBB) disruption (5 hours) and water content (24 hours) were evaluated after TBI. In groups receiving drugs or vehicle, treatment was administered as a single dose intraperitoneally 30 minutes after induction of TBI. Results Results showed that brain edema or brain water content after TBI was lower (p < 0.001) in the E2, PPT, DPN, and PPT+DPN groups than it was in the vehicle group. After trauma, the Evans blue dye content or BBB permeability was significantly higher in the TBI and vehicle groups (p < 0.001) than in the E2, PPT, DPN, and PPT+DPN groups. The inhibitory effects of PPT+DPN on brain water content, neurological scores, and Evans blue dye content were the highest for all groups. Although both PPT and DPN increased neurological scores after TBI, PPT appears to be more effective in increasing neurological scores. Conclusions Neuroprotective effects of estradiol on brain edema, BBB permeability, and neurological scores are mediated through both ERα and ERβ. This may suggest a therapeutic potential in the brain trauma for ER-specific agonists.

scholarly journals Benificial effect of stachydrine on the traumatic brain injury induced neurodegeneration by attenuating the expressions of Akt/mTOR/PI3K and TLR4/NFκ-B pathway

2018 ◽  
Vol 9 (1) ◽  
pp. 175-182 ◽  
Author(s):  
Nianzu Yu ◽  
Si Hu ◽  
Zheng Hao
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Water Content ◽  
Cognitive Dysfunction ◽  
Mammalian Target Of Rapamycin ◽  
Treated Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Western Blot Assay ◽  
The Brain

Abstract Present investigation aims to explore the protective effect of stachydrine against traumatic brain injury (TBI) and also investigate the molecular mechanism of its action. TBI was induced by the fall a hammer (450 g) from the height of 1.5 m. and later stachydrine was administered for 2 weeks starting 2 hr after the induction of TBI. Effect of stachydrine was determined by estimating modified neurological severity score (mNSS), percentage of water content in the brain and cognitive dysfunction in TBI rats. Moreover western blot assay, histopathology and enzyme linked immunosorbent assay (ELISA) tests were used to determine the effect of stachydrine on TBI injured rats. Result of the report suggests that stachydrine reduces the mNSS and percentage of water content in the brain and also attenuates the cognitive dysfunction in TBI injured rats. However data of western blot assay reports that stachydrine reduces the expression of PI3K/m-TOR/Akt pathway in the brain tissues of TBI rats. Concentration of interleukin (IL-1β), tumor necrosis factor-α (TNF-α) and interferon gamma (INF-γ) was reduces in stachydrine treated group than TBI group. Moreover expression of Nuclear factor-κB/Toll-like receptor 4 (NF-κB/TLR-4) protein was also decreased in stachydrine treated group than TBI group. Histopathology study on brain tissue reveals that the percentage of apoptotic cells was also reduced in stachydrine treated group than TBI group. Data of this investigation concludes that stachydrine protects the neuronal injury by attenuating the phosphatidylinositide 3-kinases/mammalian target of rapamycin/Protein kinase B (PI3K/m-TOR/Akt) and NF-κB/TLR-4 pathway in TBI injured rats.

FGF10 Attenuates Experimental Traumatic Brain Injury through TLR4/MyD88/NF-κB Pathway

2021 ◽  
pp. 1-9
Author(s):  
Qinhan Hou ◽  
Hongmou Chen ◽  
Quan Liu ◽  
Xianlei Yan
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Expression ◽  
Water Content ◽  
Neurological Deficit ◽  
Neuronal Apoptosis ◽  
Neuronal Damage ◽  
Intraventricular Injection ◽  
Brain Water Content ◽  
Brain Water

Traumatic brain injury (TBI) can induce neuronal apoptosis and neuroinflammation, resulting in substantial neuronal damage and behavioral disorders. Fibroblast growth factors (FGFs) have been shown to be critical mediators in tissue repair. However, the role of FGF10 in experimental TBI remains unknown. In this study, mice with TBI were established via weight-loss model and validated by increase of modified neurological severity scores (mNSS) and brain water content. Secondly, FGF10 levels were elevated in mice after TBI, whereas intraventricular injection of Ad-FGF10 decreased mNSS score and brain water content, indicating the remittance of neurological deficit and cerebral edema in TBI mice. In addition, neuronal damage could also be ameliorated by stereotactic injection of Ad-FGF10. Overexpression of FGF10 increased protein expression of Bcl-2, while it decreased Bax and cleaved caspase-3/PARP, and improved neuronal apoptosis in TBI mice. In addition, Ad-FGF10 relieved neuroinflammation induced by TBI and significantly reduced the level of interleukin 1β/6, tumor necrosis factor α, and monocyte chemoattractant protein-1. Moreover, Ad-FGF10 injection decreased the protein expression level of Toll-like receptor 4 (TLR4), MyD88, and phosphorylation of NF-κB (p-NF-κB), suggesting the inactivation of the TLR4/MyD88/NF-κB pathway. In conclusion, overexpression of FGF10 could ameliorate neurological deficit, neuronal apoptosis, and neuroinflammation through inhibition of the TLR4/MyD88/NF-κB pathway, providing a potential therapeutic strategy for brain injury in the future.

Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury

2021 ◽  
Vol 28 ◽  
Author(s):  
Lucas Alexandre Santos Marzano ◽  
Fabyolla Lúcia Macedo de Castro ◽  
Caroline Amaral Machado ◽  
João Luís Vieira Monteiro de Barros ◽  
Thiago Macedo e Cordeiro ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Hippocampal Neurogenesis ◽  
Cognitive Outcomes ◽  
Adult Hippocampal Neurogenesis ◽  
The Brain

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

Sa2015 Traumatic Brain Injury and Intestinal Dysfunction: Investigating a Putative Role of the Brain-Gut Axis in Long-Term Consequences of Injury

2015 ◽  
Vol 148 (4) ◽  
pp. S-384
Author(s):  
Elise L. Ma ◽  
Allen Smith ◽  
Neemesh Desai ◽  
Alan Faden ◽  
Terez Shea-Donohue
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Putative Role ◽  
Long Term Consequences ◽  
The Brain

scholarly journals Role of Thalamus in Recovery of Traumatic Brain Injury

2016 ◽  
Vol 07 (S 01) ◽  
pp. S076-S079 ◽  
Author(s):  
Ashok Munivenkatappa ◽  
Amit Agrawal
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Structures ◽  
Thalamic Nuclei ◽  
Posttraumatic Symptoms ◽  
Injured Brain ◽  
Recovery Mechanisms ◽  
The Brain ◽  
Degree Of Recovery

ABSTRACTDegree of recovery after traumatic brain injury is highly variable that lasts for many weeks to months. The evidence of brain structures involved in recovery mechanisms is limited. This review highlights evidence of the brain structure particularly thalamus in neuroplasticity mechanism. Thalamus with its complex global networking has potential role in refining the cortical and other brain structures. Thalamic nuclei activation both naturally or by neurorehabilitation in injured brain can enhance and facilitate the improvement of posttraumatic symptoms. This review provides evidence from literature that thalamus plays a key role in recovery mechanism after injury. The study also emphasize that thalamus should be specifically targeted in neurorehabilitation following brain injury.

scholarly journals Mitochondria-Targeted Antioxidants as Potential Therapy for the Treatment of Traumatic Brain Injury

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 124 ◽  
Author(s):  
Elena V. Stelmashook ◽  
Nickolay K. Isaev ◽  
Elisaveta E. Genrikhs ◽  
Svetlana V. Novikova
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cortical Lesion ◽  
Lesion Volume ◽  
Negative Effects ◽  
Behavioral Deficits ◽  
Secondary Damage ◽  
Long Time ◽  
The Brain ◽  
Brain Water

The aim of this article is to review the publications describing the use of mitochondria-targeted antioxidant therapy after traumatic brain injury (TBI). Recent works demonstrated that mitochondria-targeted antioxidants are very effective in reducing the negative effects associated with the development of secondary damage caused by TBI. Using various animal models of TBI, mitochondria-targeted antioxidants were shown to prevent cardiolipin oxidation in the brain and neuronal death, as well as to markedly reduce behavioral deficits and cortical lesion volume, brain water content, and DNA damage. In the future, not only a more detailed study of the mechanisms of action of various types of such antioxidants needs to be conducted, but also their therapeutic values and toxicological properties are to be determined. Moreover, the optimal therapeutic effect needs to be achieved in the shortest time possible from the onset of damage to the nervous tissue, since secondary brain damage in humans can develop for a long time, days and even months, depending on the severity of the damage.

scholarly journals Relevance of Blood Vessel Networks in Blast-Induced Traumatic Brain Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Yi Hua ◽  
Shengmao Lin ◽  
Linxia Gu
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Blood Vessel ◽  
Vessel Diameter ◽  
Dynamic Responses ◽  
Brain Dynamics ◽  
Cerebral Vasculature ◽  
Vessel Networks ◽  
The Brain

Cerebral vasculature is a complex network that circulates blood through the brain. However, the role of this networking effect in brain dynamics has seldom been inspected. This work is to study the effects of blood vessel networks on dynamic responses of the brain under blast loading. Voronoi tessellations were implemented to represent the network of blood vessels in the brain. The brain dynamics in terms of maximum principal strain (MPS), shear strain (SS), and intracranial pressure (ICP) were monitored and compared. Results show that blood vessel networks significantly affected brain responses. The increased MPS and SS were observed within the brain embedded with vessel networks, which did not exist in the case without blood vessel networks. It is interesting to observe that the alternation of the ICP response was minimal. Moreover, the vessel diameter and density also affected brain dynamics in both MPS and SS measures. This work sheds light on the role of cerebral vasculature in blast-induced traumatic brain injury.

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