Traumatic brain injury metabolome and mitochondrial impact after early stage Ru360 treatment

Traumatic brain injury (TBI) is a shocking disease frequently followed by behavioral disabilities, including risk of cerebral atrophy and dementia. N-formylpeptide receptor 1 (FPR1) is expressed in cells and neurons in the central nervous system. It is involved in inflammatory processes and during the differentiation process in the neural stem cells. We investigate the effect of the absence of Fpr1 gene expression in mice subjected to TBI from the early stage of acute inflammation to neurogenesis and systematic behavioral testing four weeks after injury. C57BL/6 animals and Fpr1 KO mice were subjected to TBI and sacrificed 24 h or four weeks after injury. Twenty-four hours after injury, TBI Fpr1 KO mice showed reduced histological impairment, tissue damage and acute inflammation (MAPK activation, NF-κB signaling induction, NRLP3 inflammasome pathway activation and oxidative stress increase). Conversely, four weeks after TBI, the Fpr1 KO mice showed reduced survival of the proliferated cells in the Dentate Gyrus compared to the WT group. Behavioral analysis confirmed this trend. Moreover, TBI Fpr1 KO animals displayed reduced neural differentiation (evaluated by beta-III tubulin expression) and upregulation of astrocyte differentiation (evaluated by GFAP expression). Collectively, our study reports that, immediately after TBI, Fpr1 increased acute inflammation, while after four weeks, Fpr1 promoted neurogenesis.

Download Full-text

Semantic memory organization during the early stage of recovery from traumatic brain injury

Brain Injury ◽

10.1080/02699050801935252 ◽

2008 ◽

Vol 22 (3) ◽

pp. 243-253 ◽

Cited By ~ 12

Author(s):

Jennifer McWilliams ◽

Maureen Schmitter-Edgecombe

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Semantic Memory ◽

Early Stage ◽

Memory Organization

Download Full-text

Lost Polarization of Aquaporin4 and Dystroglycan in the Core Lesion after Traumatic Brain Injury Suggests Functional Divergence in Evolution

BioMed Research International ◽

10.1155/2015/471631 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Hui Liu ◽

Gou ping Qiu ◽

Fei Zhuo ◽

Wei hua Yu ◽

Shan quan Sun ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Brain Edema ◽

Early Stage ◽

Functional Divergence ◽

Edema Formation ◽

Aqp4 Expression ◽

The Core ◽

Perivascular Area ◽

Brain Edema Formation

Objective. To understand how aquaporin4 (AQP4) and dystroglycan (DG) polarized distribution change and their roles in brain edema formation after traumatic brain injury (TBI).Methods. Brain water content, Evans blue detection, real-time PCR, western blot, and immunofluorescence were used.Results. At an early stage of TBI, AQP4 and DG maintained vessel-like pattern in perivascular endfeet; M1, M23, and M1/M23 were increased in the core lesion. At a later stage of TBI, DG expression was lost in perivascular area, accompanied with similar but delayed change of AQP4 expression; expression of M1, M23, and DG and the ratio of M1/M2 were increased.Conclusion. At an early stage, AQP4 and DG maintained the polarized distribution. Upregulated M1 and M23 could retard the cytotoxic edema formation. At a later stage AQP4 and DG polarized expression were lost from perivascular endfeet and induced the worst cytotoxic brain edema. The alteration of DG expression could regulate that of AQP4 expression after TBI.

Download Full-text

Prospective analysis of glycemic variability in patients with severe traumatic brain injury: modified Leuven’s adjustment process versus conventional adjustment process

Journal of International Medical Research ◽

10.1177/0300060517738396 ◽

2018 ◽

Vol 46 (4) ◽

pp. 1505-1516

Author(s):

Bing Xue ◽

Shiyan Ruan ◽

Ping Xie ◽

Kaixuan Yan ◽

Zhi'e Gu ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Blood Glucose ◽

Brain Injury ◽

Blood Glucose Level ◽

Glucose Level ◽

Severe Traumatic Brain Injury ◽

Early Stage ◽

Glycemic Variability ◽

Adjustment Process ◽

Significant Difference

Objective This study was performed to evaluate the effect of two different methods of controlling glycemic variability (GV) in patients with severe traumatic brain injury (STBI) undergoing surgery. Methods Patients with STBI were randomly grouped into a conventional adjustment process (CAP) group and modified Leuven’s adjustment process (mLAP) group. Each group included 50 patients. Blood glucose levels were continuously monitored and data were recorded and analyzed. Results The mean blood glucose level was stable in both groups for 5 days postoperatively with no significant difference. The standard deviation of the blood glucose level, mean amplitude of glycemic excursions, and glycemic lability index were significantly higher in the CAP than mLAP group for the first 2 days. In the final 3 days, no significant differences were observed between the two groups. The incidence of hypoglycemia was significantly higher in the CAP than mLAP group on the first day. This value gradually declined during the following 4 days, but the difference between the two groups was not significant. Conclusion The mLAP produced more favorable results than the CAP for GV control in the early stage after surgery for STBI.

Download Full-text

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.

Download Full-text

The effect of different atmosphere absolute hyperbaric oxygen on the expression of extracellular histones after traumatic brain injury in rats

Cell Stress and Chaperones ◽

10.1007/s12192-020-01137-6 ◽

2020 ◽

Vol 25 (6) ◽

pp. 1013-1024

Author(s):

Fang Liang ◽

Lei Sun ◽

Jing Yang ◽

Xue-Hua Liu ◽

Jing Zhang ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Hyperbaric Oxygen ◽

Early Stage ◽

Secondary Brain Injury ◽

Injury Group ◽

Extracellular Histones ◽

The One ◽

Time Specific ◽

Traumatic Brain Injury Group

Abstract By observing the dynamic changes of extracellular histones H1, H2A, H4, and NF-κB expression in brain tissues after brain injury in rats, we explore the association among the expression of extracellular histones H1, H2A, H4, and NF-κB following traumatic brain injury (TBI), as well as the effect of different atmospheres absolute hyperbaric oxygen (HBO) intervention on the expression and possible mechanisms. A total of 120 SD rats were randomly divided into 4 groups: Sham-operated (SH), TBI (traumatic brain injury) group, traumatic brain injury and hyperbaric oxygen treatment 1.6ATA (TBI + HBO1) group, and traumatic brain injury and hyperbaric oxygen treatment2.2ATA (TBI + HBO2) group, with 30 rats in each group. The rats in each group were then randomly divided into five smaller time-specific sub-groups: 3 h, 6 h, 12 h, 24 h, and 48 h after surgery. TBI models were established, and the brain tissue around the lesion was taken at different time points. On the one hand,we detected the level of local histones H1, H2A, H4, and NF-κB by RT-PCR and Western Blot. On the other hand, we used immunohistochemical methods to detect the expression of NF-κB, while using the TUNEL method to observe the cell apoptosis in experimental groups after brain injury. Extracellular histones H1, H2A, H4, and NF-κB proteins were highly expressed at 3 h, then with a slight fluctuation, reached to peak at 48 h after the injury. HBO can affect the expression of histones H1, H2A, H4, and NF-κB. The decline of each indicator in the 1.6ATA group was significantly lower than that in the 2.2ATA group, especially within 6 h (P < 0. 05). In addition, NF-κB expression was consistent with the pathological changes of apoptosis in experimental groups. Hyperbaric oxygen therapy with relatively low pressure (1.6ATA) at the early stage can significantly inhibit the expression of extracellular histones H1, H2A, H4, and NF-κB around the lesion, reduce the apoptosis of nerve cells, and thus play an important role in alleviating secondary brain injury.

Download Full-text

Axons-on-a-Chip for Mimicking Non-Disruptive Diffuse Axonal Injury underlying Traumatic Brain Injury

10.1101/2021.05.06.442958 ◽

2021 ◽

Author(s):

Wei Li ◽

Haofei Wang ◽

Xiaorong Pan ◽

Dejan Gagoski ◽

Nela Durisic ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mechanical Stress ◽

Brain Injuries ◽

Early Stage ◽

Axonal Injury ◽

Diffuse Axonal Injury ◽

Clear Correlation ◽

Pathological Feature ◽

Intracellular Changes

Diffuse axonal injury (DAI) is the most severe pathological feature of traumatic brain injury. However, how primary axonal injury is induced by mechanical stress and whether it could be mitigated remain unknown, largely due to the resolution limits of medical imaging approaches. Here we established an Axon-on-a-Chip (AoC) model for mimicking DAI and investigating its early cellular responses. By integrating computational fluid dynamics and microfluidic techniques, DAI was observed for the first time during mechanical stress, and a clear correlation between stress intensity and severity of DAI was elucidated. This AoC was further used to investigate the dynamic intracellular changes occurring simultaneously with stress, and identified delayed local Ca2+ surges escorted rapid disruption of periodic axonal cytoskeleton during the early stage of DAI. Compatible with high-resolution live-microscopy, this model hereby provides a versatile system to identify early mechanisms underlying DAI, offering a platform for screening effective treatments to alleviate brain injuries.

Download Full-text

Significance of cerebrospinal fluid inflammatory markers for diagnosing external ventricular drain–associated ventriculitis in patients with severe traumatic brain injury

Neurosurgical FOCUS ◽

10.3171/2019.8.focus19407 ◽

2019 ◽

Vol 47 (5) ◽

pp. E15 ◽

Cited By ~ 2

Author(s):

Markus Lenski ◽

Annamaria Biczok ◽

Katrin Neufischer ◽

Jörg-Christian Tonn ◽

Josef Briegel ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Inflammatory Markers ◽

Early Stage ◽

External Ventricular Drain ◽

Area Under The Curve ◽

Positive Likelihood Ratio ◽

Diagnostic Value ◽

Total Leukocyte Count ◽

Diagnostic Potential

ObjectiveThe aim of this study was to investigate the diagnostic potential of the inflammatory markers interleukin-6 (IL-6), total leukocyte count (TLC), and protein in the CSF and IL-6, C-reactive protein, and white blood cell count in the serum for the early diagnosis of ventriculitis in patients with traumatic brain injury (TBI) and an external ventricular drain compared with patients without ventriculitis.MethodsRetrospective data from 40 consecutive patients with TBI and an external ventricular drain treated in the authors’ intensive care unit between 2013 and 2017 were analyzed. For all markers, arithmetical means and standard deviations, area under the curve (AUC), cutoff values, sensitivity, specificity, positive likelihood ratio (LR), and negative LR were calculated and correlated with presence or absence of ventriculitis.ResultsThere were 35 patients without ventriculitis and 5 patients with ventriculitis. The mean ± SD IL-6 concentration in CSF was significantly increased, with 6519 ± 4268 pg/mL at onset of ventriculitis compared with 1065 ± 1705 pg/mL in patients without ventriculitis (p = 0.04). Regarding inflammatory markers in CSF, IL-6 showed the highest diagnostic potential for differentiation between the presence and absence of ventriculitis (AUC 0.938, cutoff 4064 pg/mL, sensitivity 100%, specificity 92.3%, positive LR 13, and negative LR 0), followed by TLC (AUC 0.900, cutoff 64.5 /µL, sensitivity 100%, specificity 80%, positive LR 5.0, and negative LR 0) and protein (AUC 0.876, cutoff 31.5 mg/dL, sensitivity 100%, specificity 62.5%, positive LR 2.7, and negative LR 0).ConclusionsThe level of IL-6 in CSF has the highest diagnostic value of all investigated inflammatory markers for detecting ventriculitis in TBI patients at an early stage. In particular, CSF IL-6 levels higher than the threshold of 4064 pg/mL were significantly associated with the probability of ventriculitis.

Download Full-text

Early Stage Assessment and Course of Acute Stress Disorder After Mild Traumatic Brain Injury

The Journal of Nervous and Mental Disease ◽

10.1097/nmd.0b013e318199fe7f ◽

2009 ◽

Vol 197 (3) ◽

pp. 178-181 ◽

Cited By ~ 16

Author(s):

Luke G. J. Broomhall ◽

C Richard Clark ◽

Alexander C. McFarlane ◽

Meagan OʼDonnell ◽

Richard Bryant ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Stress Disorder ◽

Acute Stress ◽

Early Stage ◽

Acute Stress Disorder

Download Full-text

518 New In Vitro Model of Traumatic Brain Injury to Assess Biomaterial Based Regenerative Strategies

British Journal of Surgery ◽

10.1093/bjs/znab135.002 ◽

2021 ◽

Vol 108 (Supplement_2) ◽

Author(s):

R H Basit ◽

S I Jenkins ◽

D M Chari

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

High Throughput ◽

Early Stage ◽

Mixed Glial Culture ◽

Vitro Model ◽

Regenerative Therapies ◽

Penetrating Traumatic Brain Injury

Abstract Introduction Penetrating traumatic brain injury (pTBI) management is largely supportive, with no clinically established regenerative therapies. Neurocompatible biomaterials offer a high potential to promote regenerative mechanisms but facile, high throughput, pathomimetic in vitro pTBI models for the developmental testing of neuro-materials is lacking. Method A mouse mixed glial culture system was utilised within which penetrating injuries could be induced. DuraGen PlusTM – an FDA approved neurosurgical grade biomaterial could be implanted into lesions to assess cell-biomaterial responses. Reactive gliosis (astrocytic morphological responses/GFAP expression) and microglial infiltration (Iba1 expression) were assessed/quantified. Results Key pathological features of pTBI were observed in the model, with the ability to (i) introduce reproducible lesions (diameter 949 ± 26 μm) and (ii) for DuraGen PlusTM to be implanted into lesions. Peri-lesional astrocytes displayed hypertrophic palisading morphologies and GFAP upregulation, analogous to gliosis in vivo. Significant microglial numbers infiltrated the DuraGen PlusTM implant at 7 days post-lesion (132.41 ± 15.83 cells/mm2) versus lesion only (82.04 ± 5.11 cells/mm2), p < 0.05). Conclusions We have developed a novel, neuropathomimetic pTBI model, wherein biomaterial implantation enables investigation of neural cell-biomaterial responses. This model can facilitate early-stage evaluation of novel biomaterials as high throughput, inexpensive and facile screening tool.

Download Full-text