The Effects of Dexmedetomidine on Trauma-Induced Secondary Injury in Rat Brain

Abstract Secondary traumatic brain injury is a potentially modifiable and important determinator of the outcome. Sedation and analgesia are common components of the therapy. However current drug therapies have disadvantages like respiratory depression. The objective of this study was to investigate the effect of dexmedetomidine (Dex), a sedative drug with little to no depressive effect on respiratory centers, on secondary injury in rat brain tissue. Eighteen rats were randomized into three groups: Trauma group received anesthesia, followed by head trauma with Mild Traumatic Brain Injury Apparatus, the Trauma+Dex group received additional treatment of 100µg/kg intraperitoneal dexmedetomidine daily for three days, The Control group received anesthesia only. Malondialdehyde (MDA), glutathione (GSH), Na+, K+-ATPase, or sodium/potassium (Na/K-ATPase), and cysteine-aspartic proteases, cysteine aspartates-3 (caspase-3) levels were measured. MDA levels were highest in the Trauma group (p = 0.002 vs Control group). Mean levels in the Trauma+Dex group were lower, albeit still significantly high compared to the Control group (p = 0.002). Glutathione levels were similar in all groups (p = 0.99). Na/K-ATPase levels were lowest in the Trauma group, which is significant compared to the Control group (p = 0.002) and the Trauma+Dex group (p = 0.026). Histopathologic findings of tissue degeneration like edema, vascular congestion and neuronal injury, and cleaved caspase-3 levels were lower in the Trauma+Dex group compared with the Trauma group. Dexmedetomidine administered during the early stage of traumatic brain injury may inhibit caspase-3 cleavage. However, the mechanism does not seem to be related to the improvement of MDA or GSH levels.

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The Effect of Pyrroloquinoline Quinone on the Expression of WISP1 in Traumatic Brain Injury

Stem Cells International ◽

10.1155/2017/4782820 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 5

Author(s):

Yongqi Ye ◽

Pengju Zhang ◽

Yuhang Qian ◽

Baoxin Yin ◽

Meijuan Yan

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Caspase 3 ◽

Negative Control Group ◽

Pyrroloquinoline Quinone ◽

Protective Role ◽

Negative Control ◽

Control Group ◽

Protective Effects ◽

Si Rna

WISP1, as a member of the CCN4 protein family, has cell protective effects of promoting cell proliferation and inhibiting cell apoptosis. Although some studies have confirmed that WISP1 is concerned with colon cancer and lung cancer, there is little report about the influence of WISP1 in traumatic brain injury. Here, we found that the expression of WISP1 mRNA and protein decreased at 3 d and then increased at 5 d after traumatic brain injury (TBI). Meanwhile, immunofluorescence demonstrated that there was little colocation of WISP1 with GFAP, Iba1, and WISP1 colocalized with NeuN partly. WISP1 colocalized with LC3, but there was little of colocation about WISP1 with cleaved caspase-3. Subsequent study displayed that the expression ofβ-catenin protein was identical to that of WISP1 after TBI. WISP1 was mainly located in cytoplasm of PC12 or SHSY5Y cells. Compared with the negative control group, WISP1 expression reduced obviously in SHSY5Y cells transfected with WISP1 si-RNA. CCK-8 assay showed that pyrroloquinoline quinone (PQQ) had little influence on viability of PC12 and SHSY5Y cells. These results suggested that WISP1 played a protective role after traumatic brain injury in rats, and this effect might be relative to autophagy caused by traumatic brain injury.

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Aquaporin 9 in rat brain after severe traumatic brain injury

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2012000300012 ◽

2012 ◽

Vol 70 (3) ◽

pp. 214-220 ◽

Cited By ~ 14

Author(s):

Hui Liu ◽

Mei Yang ◽

Guo-ping Qiu ◽

Fei Zhuo ◽

Wei-hua Yu ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Rat Brain ◽

Severe Traumatic Brain Injury ◽

Early Stage ◽

Blue Staining ◽

Tetrazolium Chloride ◽

Aquaporin 9 ◽

Polymerase Chain ◽

Two Peaks

OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9) in rat brain, after severe traumatic brain injury (TBI). METHODS: Brain water content (BWC), tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC), immunofluorescence (IF), western blot, and real-time polymerase chain reaction were used. RESULTS: The BWC reached the first and second (highest) peaks at 6 and 72 hours, and the blood brain barrier (BBB) was severely destroyed at six hours after the TBI. The worst brain ischemia occurred at 72 hours after TBI. Widespread AQP9-positive astrocytes and neurons in the hypothalamus were detected by means of IHC and IF after TBI. The abundance of AQP9 and its mRNA increased after TBI and reached two peaks at 6 and 72 hours, respectively, after TBI. CONCLUSIONS: Increased AQP9 might contribute to clearance of excess water and lactate in the early stage of TBI. Widespread AQP9-positive astrocytes might help lactate move into neurons and result in cellular brain edema in the later stage of TBI. AQP9-positive neurons suggest that AQP9 plays a role in energy balance after TBI.

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Fourier Transform Infrared Imaging—A Novel Approach to Monitor Bio Molecular Changes in Subacute Mild Traumatic Brain Injury

Brain Sciences ◽

10.3390/brainsci11070918 ◽

2021 ◽

Vol 11 (7) ◽

pp. 918

Author(s):

Fazle Rakib ◽

Khalid Al-Saad ◽

Sebnem Garip Ustaoglu ◽

Ehsan Ullah ◽

Raghvendra Mall ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Fourier Transform ◽

Brain Injury ◽

Rat Brain ◽

Mild Traumatic Brain Injury ◽

Amyloid Β ◽

Fourier Transform Infrared ◽

Control Group ◽

Ftir Imaging ◽

Imaging Results

Traumatic brain injury (TBI) can be defined as a disorder in the function of the brain after a bump, blow, or jolt to the head, or penetrating head injury. Mild traumatic brain injury (mTBI) can cause devastating effects, such as the initiation of long-term neurodegeneration in brain tissue. In the current study, the effects of mTBI were investigated on rat brain regions; cortex (Co) and corpus callosum (CC) after 24 h (subacute trauma) by Fourier transform infrared (FTIR) imaging and immunohistochemistry (IHC). IHC studies showed the formation of amyloid-β (Aβ) plaques in the cortex brain region of mTBI rats. Moreover, staining of myelin basic protein presented the shearing of axons in CC region in the same group of animals. According to FTIR imaging results, total protein and lipid content significantly decreased in both Co and CC regions in mTBI group compared to the control. Due to this significant decrease in both lipid and protein content, remarkable consistency in lipid/protein band ratio in mTBI and control group, was observed. Significant decrease in methyl content and a significant increase in olefinic content were observed in Co and CC regions of mTBI rat brain tissues. Classification amongst distinguishable groups was performed using principal component analysis (PCA) and hierarchical clustering (HCA). This study established the prospective of FTIR imaging for assessing biochemical changes due to mTBI with high sensitivity, precision and high-resolution.

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Catechins decrease neurological severity score through apoptosis and neurotropic factor pathway in rat traumatic brain injury

Zinc supplementation improves heme biosynthesis in rats exposed to lead ◽

10.18051/univmed.2017.v36.110-122 ◽

2017 ◽

Vol 36 (2) ◽

pp. 110

Author(s):

Retty Ratnawati ◽

Annisa Nurul Arofah ◽

Anastasia Novitasari ◽

Sartika Dewi Utami ◽

Made Ayu Hariningsih ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Severity Score ◽

Caspase 3 ◽

Negative Control Group ◽

Positive Control ◽

Negative Control ◽

Control Group ◽

Caspase 8 ◽

Neurotropic Factor

BACKGROUND Catechins inhibits apoptosis through anti oxidant and anti inflamation pathway. Catechins also increases brain-derived neurotrophic factor (BDNF). There was a few research that explained the role of catechins in traumatic brain injury (TBI). The objective of the study was to evaluate the effect of catechins administration on neurologic severity score (NSS) through apoptosis and neurotropic pathway in traumatic brain injury rat model.METHODS A post test only controlled group design was performed using traumatic brain injury rat (Rattus novergicus) model through weight drop models. It was devided into negative control group, positive control group, TBI+catechins 513 mg/kgBW, TBI+catechins 926 mg/kgBW, TBI+catechins 1113 mg/kgBW. NSS was measured in the first hours, day three, and day seven. The expressions of NFkB, TNFa, Bcl-2, Bax, caspase 3, caspase 8, BDNF, and the numbers of apoptosis cells were evaluated by imunohistochemystry method. One way Anova and Kruskal Wwallis were used to analyse the data.Results TNFa, caspase 8, number of apoptosis cells were significantly decreased on the seventh day administration compared to the third day administration (p<0.05). Catechins increased the expression of Bcl-2/Bax and BDNF significantly (p<0.05). Yet, there were no significant differences between expression of caspase 3, NSS, Bcl-2/Bax ratio, and BDNF toward third days administration of catechins compared with seven days administration (p>0.050).Conclusions Administration of catechins decreased NSS through inhibiting inflammation and apoptosis, as well as induced the neurotrophic factors in rat brain injury. Catechins may serve as a potential intervention for TBI.

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Concurrent calpain and caspase-3 mediated proteolysis of αII-spectrin and tau in rat brain after methamphetamine exposure: A similar profile to traumatic brain injury

Life Sciences ◽

10.1016/j.lfs.2005.04.058 ◽

2005 ◽

Vol 78 (3) ◽

pp. 301-309 ◽

Cited By ~ 46

Author(s):

Matthew W. Warren ◽

Firas H. Kobeissy ◽

Ming Cheng Liu ◽

Ronald L. Hayes ◽

Mark S. Gold ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Rat Brain ◽

Caspase 3 ◽

Similar Profile

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Endothelial glycocalyx degradation is associated with early organ impairment in polytrauma patients

BMC Emergency Medicine ◽

10.1186/s12873-021-00446-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Feng Qi ◽

Hao Zhou ◽

Peng Gu ◽

Zhi-He Tang ◽

Bao-Feng Zhu ◽

...

Keyword(s):

Injury Severity ◽

Early Stage ◽

Endothelial Glycocalyx ◽

Control Group ◽

Metabolic System ◽

Metabolic Systems ◽

Organ Systems ◽

Severity Scores ◽

Polytrauma Patients ◽

Trauma Group

Abstract Background Endothelial glycocalyx (EG) abnormal degradation were widely found in critical illness. However, data of EG degradation in multiple traumas is limited. We performed a study to assess the EG degradation and the correlation between the degradation and organ functions in polytrauma patients. Methods A prospective observational study was conducted to enroll health participants (control group) and polytrauma patients (trauma group) at a University affiliated hospital between Feb 2020 and Oct 2020. Syndecan1 (SDC1) and heparin sulfate (HS) were detected in serum sample of both groups. In trauma group, injury severity scores (ISS) and sequential organ failure assessments (SOFA) were calculated. Occurrences of acute kidney injury (AKI), trauma-induced coagulopathy (TIC) within 48 h and 28-day all-cause mortality in trauma group were recorded. Serum SDC1 and HS levels were compared between two groups. Correlations between SDC1/HS and the indicators of organ systems in the trauma group were analyzed. ROC analyses were performed to assess the predictive value of SDC1 and HS for AKI, TIC within 48 h, and 28-day mortality in trauma group. Results There were 45 polytrauma patients and 15 healthy participants were collected, totally. SDC1 and HS were significantly higher in trauma group than in control group (69.39 [54.18–130.80] vs. 24.15 [13.89–32.36], 38.92 [30.47–67.96] vs. 15.55 [11.89–23.24], P < 0.001, respectively). Trauma group was divided into high degradation group and low degradation group according to SDC1 median. High degradation group had more severe ISS, SOFA scores, worse organ functions (respiratory, kidney, coagulation and metabolic system), and higher incidence of hypothermia, acidosis and shock. The area under the receiver operator characteristic curves (AUC) of SDC1 to predict AKI, TIC occurrence within 48 h and 28-day mortality were 0.838 (95%CI: 0.720–0.957), 0.700 (95%CI: 0.514–0.885) and 0.764 (95%CI: 0.543–0.984), respectively. Conclusions EG degradation was elevated significantly in polytrauma patients, and the degradation was correlated with impaired respiratory, kidney, coagulation and metabolic systems in early stage. Serum SDC1 is a valuable predictive indicator of early onset of AKI, TIC, and 28-day mortality in polytrauma patients.

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Remotely delivered environmental enrichment intervention for traumatic brain injury: Study protocol for a randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2020-039767 ◽

2021 ◽

Vol 11 (2) ◽

pp. e039767

Author(s):

Zorry Belchev ◽

Mary Ellene Boulos ◽

Julia Rybkina ◽

Kadeen Johns ◽

Eliyas Jeffay ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Active Control ◽

Environmental Enrichment ◽

Spatial Navigation ◽

Controlled Trial ◽

Control Group ◽

Hippocampal Atrophy ◽

Active Control Group ◽

Navigation Group

IntroductionIndividuals with moderate-severe traumatic brain injury (m-sTBI) experience progressive brain and behavioural declines in the chronic stages of injury. Longitudinal studies found that a majority of patients with m-sTBI exhibit significant hippocampal atrophy from 5 to 12 months post-injury, associated with decreased cognitive environmental enrichment (EE). Encouragingly, engaging in EE has been shown to lead to neural improvements, suggesting it is a promising avenue for offsetting hippocampal neurodegeneration in m-sTBI. Allocentric spatial navigation (ie, flexible, bird’s eye view approach), is a good candidate for EE in m-sTBI because it is associated with hippocampal activation and reduced ageing-related volume loss. Efficacy of EE requires intensive daily training, prohibitive within most current health delivery systems. The present protocol is a novel, remotely delivered and self-administered intervention designed to harness principles from EE and allocentric spatial navigation to offset hippocampal atrophy and potentially improve hippocampal functions such as navigation and memory for patients with m-sTBI.Methods and analysisEighty-four participants with chronic m-sTBI are being recruited from an urban rehabilitation hospital and randomised into a 16-week intervention (5 hours/week; total: 80 hours) of either targeted spatial navigation or an active control group. The spatial navigation group engages in structured exploration of different cities using Google Street View that includes daily navigation challenges. The active control group watches and answers subjective questions about educational videos. Following a brief orientation, participants remotely self-administer the intervention on their home computer. In addition to feasibility and compliance measures, clinical and experimental cognitive measures as well as MRI scan data are collected pre-intervention and post-intervention to determine behavioural and neural efficacy.Ethics and disseminationEthics approval has been obtained from ethics boards at the University Health Network and University of Toronto. Findings will be presented at academic conferences and submitted to peer-reviewed journals.Trial registration numberVersion 3, ClinicalTrials.gov Registry (NCT04331392).

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