scholarly journals Time-dependent cytokine and chemokine changes in mouse cerebral cortex following a mild traumatic brain injury

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
David Tweedie ◽  
Hanuma Kumar Karnati ◽  
Roger Mullins ◽  
Chaim G Pick ◽  
Barry J Hoffer ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Extracellular Vesicle ◽  
Neurological Dysfunction ◽  
Physiological Processes ◽  
Mouse Cerebral Cortex ◽  
Weight Drop ◽  
Altered Proteins ◽  
Response Biomarkers ◽  
Global Health Problem

Traumatic brain injury (TBI) is a serious global health problem, many individuals live with TBI-related neurological dysfunction. A lack of biomarkers of TBI has impeded medication development. To identify new potential biomarkers, we time-dependently evaluated mouse brain tissue and neuronally derived plasma extracellular vesicle proteins in a mild model of TBI with parallels to concussive head injury. Mice (CD-1, 30–40 g) received a sham procedure or 30 g weight-drop and were euthanized 8, 24, 48, 72, 96 hr, 7, 14 and 30 days later. We quantified ipsilateral cortical proteins, many of which differed from sham by 8 hours post-mTBI, particularly GAS-1 and VEGF-B were increased while CXCL16 reduced, 23 proteins changed in 4 or more of the time points. Gene ontology pathways mapped from altered proteins over time related to pathological and physiological processes. Validation of proteins identified in this study may provide utility as treatment response biomarkers.

scholarly journals Influence of Glutamine on Intestinal Inflammatory Response, Mucosa Structure Alterations and Apoptosis following Traumatic Brain Injury in Rats

2007 ◽  
Vol 35 (5) ◽  
pp. 644-656 ◽  
Author(s):  
D Feng ◽  
W Xu ◽  
G Chen ◽  
C Hang ◽  
H Gao ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Intestinal Inflammation ◽  
Glutamine Supplementation ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Tissue Samples ◽  
Weight Drop ◽  
Factor Α

Traumatic brain injury (TBI) can induce a persistent inflammatory response, histopathological changes and apoptosis in the intestine. Glutamine has been shown to reduce bacterial translocation and maintain intestine mucosal integrity, but its effects on the inflammatory response, structural alterations and apoptosis in intestinal mucosa following TBI have not been previously investigated. Using the weight-drop method, a right parietal cortical contusion was induced in rats and, for the next 5 days, they were fed either chow alone or chow mixed with glutamine. Intestinal tissue samples were then removed for analysis. Following TBI, glutamine supplementation was found to: decrease intestinal concentrations of interleukin (IL) −1β, tumour necrosis factor-α (TNF-α) and IL-6; downregulate intercellular adhesion molecule-1 (ICAM-1) expression; attenuate TBI-induced damage to the intestine structure; and reduce apoptosis. These results suggest that post-TBI glutamine administration could suppress intestinal inflammation, protect intestinal mucosal structure and reduce mucosal apoptosis.

Amyloid-β Protein and Neuroglobin Protein as Biomarkers on Brainstem Following Traumatic Brain Injury in Rats

2020 ◽  
Author(s):  
Wenhe Li ◽  
Haijun Zhu ◽  
Yue Liang ◽  
Fang Tong ◽  
Yiwu Zhou
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Damage ◽  
Amyloid Β ◽  
Immunofluorescence Assay ◽  
Amyloid Β Protein ◽  
Sprague Dawley ◽  
Specific Expression ◽  
Western Blot Assay ◽  
Weight Drop

Abstract Background: Biomarkers play an important role in accurate diagnosis of traumatic brain injury (TBI). Due to the complexity and diversity of TBI, it is likely that a single biomarker will not be used for exactly diagnose. Amyloid-beta (Aβ) protein is generated by sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretase, which may exert its toxic effects by increasing reactive oxygen species and neuroinflammation in the brain as damage factor of TBI. Its use in diagnosis for TBI is becoming more widespread. Neuroglobin (NGB) protein is great potential to diminish neuronal damage. Most epidemiological evidence suggested that Aβ and NGB may be used as biomarkers on brainstem (BS) following TBI. The aim of this study was to investigate the trend of Aβ and NGB on BS of rats with TBI and to analyze comprehensively them as potential biomarkers. Methods: Adult male Sprague-Dawley rats were subjected to the modified weight-drop model of closed TBI. Biologic behavior observation, histopathological assessments and western blot assay were performed. Aβ and NGB expression indicated temporal changes in BS after TBI. Their accuracy and efficiency of performing these tasks were calculated and statistical comparisons performed.Results: The results of Aβ enable us to speculate that the time points of 3 h, 6 h and 12 h may be crucial points for the diagnosis of TBI. NGB expression in the injured had obvious difference versus the control, the points of 1 h and 3 h were apparently higher than the control, and the groups of 12 h and 48 h were two peaks in the present study. Furthermore, the immunofluorescence assay results supported that Aβ and NGB co-localization in the neuros of BS, and the NGB specific expression in the BS of neurons.Conclusions: Therefore, the expression and change rules of Aβ and NBG in the BS may provide an important foundation for the diagnosis of TBI, damage assessment and therapeutic intervention.

scholarly journals A combination antioxidant therapy to inhibit NOX2 and activate Nrf2 decreases secondary brain damage and improves functional recovery after traumatic brain injury

2017 ◽  
Vol 38 (10) ◽  
pp. 1818-1827 ◽  
Author(s):  
Raghavendar Chandran ◽  
TaeHee Kim ◽  
Suresh L Mehta ◽  
Eshwar Udho ◽  
Vishal Chanana ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Motor Function ◽  
Neurological Dysfunction ◽  
Vehicle Group ◽  
Lesion Volume ◽  
Post Injury ◽  
Cortical Contusion ◽  
Nrf2 Activator

Uncontrolled oxidative stress contributes to the secondary neuronal death that promotes long-term neurological dysfunction following traumatic brain injury (TBI). Surprisingly, both NADPH oxidase 2 (NOX2) that increases and transcription factor Nrf2 that decreases reactive oxygen species (ROS) are induced after TBI. As the post-injury functional outcome depends on the balance of these opposing molecular pathways, we evaluated the effect of TBI on the motor and cognitive deficits and cortical contusion volume in NOX2 and Nrf2 knockout mice. Genetic deletion of NOX2 improved, while Nrf2 worsened the post-TBI motor function recovery and lesion volume indicating that decreasing ROS levels might be beneficial after TBI. Treatment with either apocynin (NOX2 inhibitor) or TBHQ (Nrf2 activator) alone significantly improved the motor function after TBI, but had no effect on the lesion volume, compared to vehicle control. Whereas, the combo therapy (apocynin + TBHQ) given at either 5 min/24 h or 2 h/24 h improved motor and cognitive function and decreased cortical contusion volume compared to vehicle group. Thus, both the generation and disposal of ROS are important modulators of oxidative stress, and a combo therapy that prevents ROS formation and potentiates ROS disposal concurrently is efficacious after TBI.

scholarly journals Micro Ribonucleic Acid Profiles of Traumatic Brain Injury Isolated From Plasma Extracellular Vesicles

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Ross Puffer ◽  
Luz Cumba-Garcia ◽  
Benjamin T Himes ◽  
David O Okonkwo ◽  
Ian F Parney
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Extracellular Vesicles ◽  
Rna Isolation ◽  
Extracellular Vesicle ◽  
Micro Rna ◽  
Altered Consciousness ◽  
Rna Sequences ◽  
Altered Level ◽  
Level Of Consciousness

Abstract INTRODUCTION Extracellular vesicles (EVs) are membrane-bound particles released by the majority of human cells, including cells within the central nervous system. They may represent a diagnostic or prognostic target obtainable in peripheral blood of neurotrauma patients. We have isolated micro RNA sequences contained within EVs of 15 patients with traumatic brain injury (TBI) and compared them to miRNA sequences from 5 healthy controls. METHODS Extracellular vesicles were isolated from 15 TBI subjects, including 6 mild TBI (Glasgow Coma Scale (GCS) 13-15), 3 moderate TBI (GCS 9-12), and 6 severe TBI (GCS 3-8), as well as 5 healthy control. EVs were analyzed using nanoparticle tracking analysis. Samples underwent RNA isolation and extraction, followed by miRNA sequencing and analysis. RESULTS TBI patients presenting with an altered level of consciousness (GCS = 14) had a significantly higher mean extracellular vesicle size compared to subjects with normal GCS (mean + /− sem = 108.3 nm + /− 7.7 nm vs 89.2 nm + /− 6.7 nm; P < .04). GFAP ELISA of the samples demonstrated significantly higher GFAP concentration in subjects with altered level of consciousness (GCS = 14) as compared to those with normal GCS (mean + /− sem GFAP concentration 2204.2 pg/mL + /− 1067.2 pg/mL vs. 207.8 pg/mL + /− 270.8 pg/mL, P = .05). We identified 9 miRNA sequences that were found in a significantly higher proportion in patients with altered consciousness compared to controls, as well as 2 miRNA sequences that were significantly downregulated in subjects with altered consciousness as compared to controls. CONCLUSION EVs may contain brain specific biomarkers that are released in greater quantities after TBI. These molecules can be isolated from plasma and sequenced. Further analysis will better elucidate the final pathways affected by these up and downregulated miRNA sequences. Analysis of EVs in subjects with TBI may allow for the identification of novel diagnostic and potentially prognostic biomarkers.

Novel Rat Model of Weight Drop-Induced Closed Diffuse Traumatic Brain Injury Compatible with Electrophysiological Recordings of Vigilance States

2016 ◽  
Vol 33 (13) ◽  
pp. 1171-1180 ◽  
Author(s):  
Fabian Büchele ◽  
Marta M. Morawska ◽  
Sebastian R. Schreglmann ◽  
Marco Penner ◽  
Markus Muser ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rat Model ◽  
Electrophysiological Recordings ◽  
Weight Drop

scholarly journals Comparative Neuroprotective Effects of Cyclosporin a and NIM811, a Nonimmunosuppressive Cyclosporin a Analog, following Traumatic Brain Injury

2008 ◽  
Vol 29 (1) ◽  
pp. 87-97 ◽  
Author(s):  
Lamin Han Mbye ◽  
Indrapal N Singh ◽  
Kimberly M Carrico ◽  
Kathryn E Saatman ◽  
Edward D Hall
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cyclosporin A ◽  
Mitochondrial Dysfunction ◽  
Motor Function ◽  
Neurological Dysfunction ◽  
Neuroprotective Effects ◽  
Function Impairment ◽  
Calcineurin Inhibition ◽  
Experimental Traumatic Brain Injury

Earlier experiments have shown that cyclosporin A (CsA) and its non-calcineurin inhibitory analog NIM811 attenuate mitochondrial dysfunction after experimental traumatic brain injury (TBI). Presently, we compared the neuroprotective effects of previously determined mitochondrial protective doses of CsA (20 mg/kg intraperitoneally) and NIM811 (10 mg/kg intraperitoneally) when administered at 15 mins postinjury in preventing cytoskeletal (α-spectrin) degradation, neuro-degeneration, and neurological dysfunction after severe (1.0 mm) controlled cortical impact (CCI) TBI in mice. In a first set of experiments, we analyzed calpain-mediated α-spectrin proteolysis at 24 h postinjury. Both NIM811 and CsA significantly attenuated the increased α-spectrin breakdown products observed in vehicle-treated animals ( P < 0.005). In a second set of experiments, treatment of animals with either NIM811 or CsA at 15 mins and again at 24 h postinjury attenuated motor function impairment at 48 h and 7 days ( P < 0.005) and neurodegeneration at 7 days postinjury ( P < 0.0001). Delayed administration of NIM811 out to 12 h was still able to significantly reduce α-spectrin degradation. These results show that the neuroprotective mechanism of CsA involves maintenance of mitochondrial integrity and that calcineurin inhibition plays little or no role because the non-calcineurin inhibitory analog, NIM811, is as effective as CsA.

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