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.

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.

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.

Effects of Traumatic Brain Injury on Arachidonic Acid Metabolism and Brain Water Content in the Rat

1989 ◽  
Vol 559 (1 Arachidonie A) ◽  
pp. 431-432 ◽  
Author(s):  
PAUL DEMEDIUK ◽  
ALAN I. FADEN ◽  
ROBERT VINK ◽  
ROBERT ROMHANYI ◽  
TRACY K. McINTOSH
Keyword(s):  
Traumatic Brain Injury ◽  
Arachidonic Acid ◽  
Brain Injury ◽  
Water Content ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Brain Water Content ◽  
Brain Water

scholarly journals Sex Differences in Cerebral Edema after Experimental Traumatic Brain Injury

2021 ◽  
Author(s):  
Heather M Minchew ◽  
Sarah K Christian ◽  
Paul Keselman ◽  
Jinxiang Hu ◽  
Brian T Andrews ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Sex Differences ◽  
Brain Injury ◽  
Water Content ◽  
Cerebral Edema ◽  
Contralateral Side ◽  
Female Rats ◽  
Male Rats ◽  
Brain Water Content ◽  
Brain Water

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Cerebral edema following TBI is known to play a critical role in injury severity and prognosis. In the current study we used multimodal magnetic resonance imaging (MRI) to assess cerebral edema 24 hours after unilateral contusive TBI in male and female rats. We then directly quantified brain water content in the same subjects ex vivo. We found that in male rats, the injured cortex had higher brain water content and lower apparent diffusion coefficient (ADC) values compared with the contralateral side. Females did not show hemispheric differences for these measures. However, both males and females had similarly elevated T2 values in the injured cortex compared with the contralateral side. A strong correlation was observed between brain water content and T2 values in the injured cortex in male rats, but not in females. These findings raise questions about the clinical interpretation of radiological findings pertinent to edema in female TBI patients. A more mechanistic understanding of sex differences and similarities in TBI pathophysiology will help improve patient management and the development of effective treatment strategies for TBI in men and women.

scholarly journals The Activation of Phosphatidylserine/CD36/TGF-β1 Pathway prior to Surgical Brain Injury Attenuates Neuroinflammation in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Lei Huang ◽  
Hailiang Tang ◽  
Prativa Sherchan ◽  
Cameron Lenahan ◽  
Warren Boling ◽  
...  
Keyword(s):  
Brain Injury ◽  
Water Content ◽  
Neurological Deficits ◽  
Preventive Strategy ◽  
Neurosurgical Procedures ◽  
Brain Water Content ◽  
Protein Levels ◽  
Surgical Brain Injury ◽  
Brain Water ◽  
Brain Tissues

Neuroinflammation plays an important pathological role in experimental surgical brain injury (SBI). Apoptotic associated with phosphatidylserine (PS) externalization promotes anti-inflammatory mediator TGF-β1 release. In the present study, we investigated the anti-neuroinflammation effect of PS liposome or isoflurane pretreatment via PS/CD36/TGF-β1 signaling in a rat model of SBI. A total of 120 male Sprague-Dawley rats (weighing 280-330 gms) were used. SBI was induced by partial right frontal lobe corticotomy. Intranasal PS liposome or isoflurane inhalation was administered prior to SBI induction. CD36 small interfering RNA (siRNA) was administered intracerebroventricularly. Recombinant Annexin V protein (rAnnexin V) was delivered intranasally. Post-SBI assessments included neurological tests, brain water content, Western blot, and immunohistochemistry. Endogenous CD36 protein levels but not TGF-β1 was significantly increased within peri-resection brain tissues over 72 h after SBI. SBI rats were associated with increased brain water content surrounding corticotomy and neurological deficits. PS liposome pretreatment significantly reduced brain water content and improved some neurological deficits at 24 hours and 72 hours after SBI. PS liposome increased CD36 and TGF-β1 protein levels, but decreased IL-1β and TNFα protein levels in peri-resection brain tissues at 24 hours after SBI. CD36 siRNA or rAnnexin V partially countered the protective effect of PS liposome. Isoflurane pretreatment produced similar antineuroinflammation and neurological benefits in SBI rats partially by upregulating CD36/Lyn/TGF-β1 signaling. Collectively, our findings suggest that the activation of PS/CD36/TGF-β1 pathway by PS liposome or isoflurane prior to SBI could attenuate neuroinflammation and improve neurological outcomes in rats. PS liposome or isoflurane pretreatment may serve as an effective preventive strategy to minimize the brain injury caused by neurosurgical procedures in patients.

scholarly journals The Antiedematous Effect of Exogenous Lactate Therapy in Traumatic Brain Injury: A Physiological and Mechanistic Approach

2021 ◽  
Author(s):  
David Emmanuel Duhaut ◽  
Catherine Heurteaux ◽  
Carine Gandin ◽  
Carole Ichai ◽  
Hervé Quintard
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Water Content ◽  
Oxygen Pressure ◽  
Chloride Channels ◽  
Brain Water Content ◽  
Tissue Oxygen ◽  
Cerebral Tissue ◽  
Brain Water ◽  
Tissue Oxygen Pressure

Abstract Background Sodium lactate (SL) has been described as an efficient therapy in treating raised intracranial pressure (ICP). However, the precise mechanism by which SL reduces intracranial hypertension is not well defined. An antiedematous effect has been proposed but never demonstrated. In this context, the involvement of chloride channels, aquaporins, or K–Cl cotransporters has also been suggested, but these mechanisms have never been assessed when using SL. Methods In a rat model of traumatic brain injury (TBI), we compared the effect of SL versus mannitol 20% on ICP, cerebral tissue oxygen pressure, and brain water content. We attempted to clarify the involvement of chloride channels in the antiedematous effects associated with lactate therapy in TBI. Results An equimolar single bolus of SL and mannitol significantly reduced brain water content and ICP and improved cerebral tissue oxygen pressure 4 h after severe TBI. The effect of SL on brain water content was much longer than that of mannitol and persisted at 24 h post TBI. Western blot and immunofluorescence staining analyses performed 24 h after TBI revealed that SL infusion is associated with an upregulation of aquaporin 4 and K–Cl cotransporter 2. Conclusions SL is an effective therapy for treating brain edema after TBI. This study suggests, for the first time, the potential role of chloride channels in the antiedematous effect induced by exogenous SL.

scholarly journals Mechanism of Baicalein in Brain Injury After Intracerebral Hemorrhage by Inhibiting the ROS/NLRP3 Inflammasome Pathway

2021 ◽  
Author(s):  
Xuan Chen ◽  
Yue Zhou ◽  
Shanshan Wang ◽  
Wei Wang
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Water Content ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Factors ◽  
Brain Water Content ◽  
Ros Scavenger ◽  
The Brain ◽  
Brain Water

Abstract Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high disability/mortality. Baicalein has strong anti-inflammatory activity. This study aims to explore the mechanism of baicalein on brain injury after ICH. The model of brain injury after ICH was established by collagenase induction, followed by the evaluation of neurological severity, brain water content, the degenerated neurons, neuronal apoptosis and reactive oxygen species (ROS). The ICH model was treated with baicalein and silencing NLRP3 to detect brain injury. The expression of NLRP3 inflammasome was detected after treatment with ROS scavenger. The expression of oxidative stress markers and inflammatory factors were detected, and the levels of components in NLRP3 inflammasome were detected. Baicalein reduced the damage of nervous system, lesion surface, brain water content and apoptosis. Baicalein inhibited malondialdehyde and increased IL-10 by inhibiting ROS in brain tissue after ICH. Baicalein inhibited the high expression of NLRP3 inflammasome in ICH. ROS scavenger inhibited the NLRP3 inflammatory response by inhibiting ROS levels. Silencing NLRP3 alleviated the brain injury after ICH by inhibiting excessive oxidative stress and inflammatory factors. Overall, baicalein alleviated the brain injury after ICH by inhibiting ROS and NLRP3 inflammasome.

scholarly journals Sevoflurane Inhibits Traumatic Brain Injury-Induced Neuron Apoptosis via EZH2-Downregulated KLF4/p38 Axis

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhongyu Wang ◽  
Juan Li ◽  
Anqi Wang ◽  
Zhaoyang Wang ◽  
Junmin Wang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Water Content ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Brain Water Content ◽  
Brain Water ◽  
Neuron Apoptosis

Traumatic brain injury (TBI) is characterized by physical damage to the brain tissues, ensuing transitory or permanent neurological dysfunction featured with neuronal loss and subsequent brain damage. Sevoflurane, a widely used halogenated anesthetic in clinical settings, has been reported to alleviate neuron apoptosis in TBI. Nevertheless, the underlying mechanism behind this alleviation remains unknown, and thus was the focus of the current study. First, Feeney models were established to induce TBI in rats. Subsequently, evaluation of the modified neurological severity scores, measurement of brain water content, Nissl staining, and TUNEL assay were employed to investigate the neuroprotective effects of sevoflurane. Immunofluorescence and Western blot analysis were further applied to detect the expression patterns of apoptosis-related proteins as well as the activation of the p38-mitogen-activated protein kinase (MAPK) signaling pathway within the lesioned cortex. Additionally, a stretch injury model comprising cultured neurons was established, followed by neuron-specific enolase staining and Sholl analysis. Mechanistic analyses were performed using dual-luciferase reporter gene and chromatin immunoprecipitation assays. The results demonstrated sevoflurane treatment brought about a decrease blood-brain barrier (BBB) permeability, brain water content, brain injury and neuron apoptosis, to improve neurological function. The neuroprotective action of sevoflurane could be attenuated by inactivation of the p38-MAPK signaling pathway. Mechanistically, sevoflurane exerted an inhibitory effect on neuron apoptosis by up-regulating enhancer of zeste homolog 2 (EZH2), which targeted Krüppel-like factor 4 (KLF4) and inhibited KLF4 transcription. Collectively, our findings indicate that sevoflurane suppresses neuron apoptosis induced by TBI through activation of the p38-MAPK signaling pathway via the EZH2/KLF4 axis, providing a novel mechanistic explanation for neuroprotection of sevoflurane in TBI.

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