Correlation of ultrastructural changes of endothelial cells and astrocytes occuring during blood brain barrier damage after traumatic brain injury with biochemical markers of BBB leakage and inflammatory response

Focal cerebral contusion can be dynamic and expansive. It has been proved that subsequent expansive contusion is caused by brain parenchyma damage, especially BBB damage. We investigated a group of patients with traumatic brain injury. The patients (n=18) were divided into group I (n=7) of patients submitted to neurosurgery due to expansive contusion, and group II (n=11) of patients without surgery. Serum concentrations of NSE and S-100B protein were measured by electrochemiluminescence immunoassay, interleukin-6 (IL-6) was measured by chemiluminescent sequential immunometric assay and matrix metalloproteinases (MMP-9, MMP-2) were measured by immunoassays. Cortical biopsy specimens of brain were investigated by electron microscopy in patients with trauma brain injury submitted to neurosurgery. Biochemical investigation from first day up to third day after traumatic brain injury proved increased values of IL-6 (302.2±119.9 vs. 59.6±11.9 ng/l, p<0.02) and S-100B protein (3.064±1.064 vs. 0.649±0.182 μg/l, p<0.05) in patients with expansive lesion compared to patients without expansive contusion. Significantly higher levels of MMP-9 (150.4±28.46 vs. 74.11±13.16 ng/l, p<0.05) and of MMP-2 (814.5±126.3 vs. 523.1±25.28 ng/l, p<0.05) were found during first 3 days after admission in group I compared to group II. MMP-9 has also elevated in group II from lower values after admission (74.11±13.16 ng/l) up to high levels on the 10th day of hospitalization (225.1±49.35 ng/l). Ultrastructural investigation of endothelial cells and surrounded tissue revealed perivascular hemorrhage, increased pinocytic activity of endothelial cells, and cytotoxic edema of astroglial cells. Multivesical bodies were disclosed inside the endothelial cells. Higher levels of serum protein S-100B and IL-6 correlated with ultrastructural changes of endothelial cells, and with inflammatory response following TBI, respectively.

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Regional cerebrovascular responses to progressive hypotension after traumatic brain injury in cats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1992.263.4.h1276 ◽

1992 ◽

Vol 263 (4) ◽

pp. H1276-H1284 ◽

Cited By ~ 3

Author(s):

D. S. DeWitt ◽

D. S. Prough ◽

C. L. Taylor ◽

J. M. Whitley ◽

D. D. Deal ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Brain Regions ◽

Group Iv ◽

Group Iii ◽

Hemorrhagic Hypotension ◽

Isoflurane Anesthesia ◽

Group I ◽

Injury Group ◽

Group Ii

We investigated the effects of hypotension on cerebral blood flow (CBF) after traumatic brain injury (TBI) in cats. Isoflurane-anesthetized cats were prepared for TBI and for microsphere measurements of total (T) and regional (r) CBF. Four groups were studied: sham injury (group I, n = 6); TBI (group II, n = 6); isoflurane anesthesia, no TBI or hypotension (group III, n = 4); and isoflurane and TBI, no hypotension (group IV, n = 8). After TBI or sham trauma, mean arterial pressure (MAP) was reduced to 80, 60, and 40 mmHg by hemorrhage. Group I TCBF did not change significantly from baseline until MAP reached 40 mmHg, but rCBF was more dependent on MAP in anterior hemispheric than in brain stem regions. Group II TCBF was significantly lower than baseline, and group I TCBF at all levels of hypotension and autoregulation was impaired at higher MAP levels in anterior than in posterior brain regions. Groups III and IV indicated that decreases in TCBF were not due to duration of the preparation or to TBI in the absence of hemorrhagic hypotension. We conclude that global and regional autoregulation are absent in response to hemorrhagic hypotension after TBI.

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Traumatic Brain Injury: Prognostic Value of Various Coma Scales, CT Scores & Their Comparison Based on Clinical Outcome

Galore International Journal of Health Sciences and Research ◽

10.52403/gijhsr.20210705 ◽

2021 ◽

Vol 6 (3) ◽

pp. 26-30

Author(s):

Ashrit Reddy Cheruku ◽

Suryanarayan Reddy V

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Glasgow Coma Scale ◽

Group Iv ◽

Coma Scale ◽

Group I ◽

Highly Sensitive ◽

Four Score ◽

Group Ii ◽

Gcs Score

Background: Traumatic brain injury (TBI) is common, carries a high morbidity and mortality and has no specific treatment. The Glasgow coma scale (GCS) is considered the gold standard for assessment of unconsciousness in patients with traumatic brain injury against which other scale are compared to overcome the disadvantages of GCS. Materials & Methods: This is Prospective Observational comparative study was conducted in total 128 who admitted with traumatic brain injury (TBI) in Department of General Surgery, Chalmeda Anand Rao Institute of Medical Sciences, Karimnagar during the period from November 2016 to November 2018. Results: A total of 128 (112 males) patients were included in the study. Among SMS, 0 is highly sensitive (72.22%), 2 is highly specific (80.43%). In GCS score < 8 was highly sensitive (97.22%) & GCS score 9 - 12 was highly specific (82.61%). In this study Marshall CT score of 4 - 6 (group II) has mortality 43.55% & CT score 1 - 3 (group I) was 13.64%. Where as in Rotterdam CT score was significant mortality with score 4 - 6 (group II) was 56.25% & CT score of 1 - 3 (group I) was 24.11%. In FOUR score with GCS, on 1 day with FOUR score 13 - 16 (group IV) has 5.56%, day 3, 13 - 16 (group IV) has 3.45%, day 7, 13 - 16 (group IV) has 3.13% & day 21, 13 - 16 (group IV) only 3.45% has mortality rate. Conclusion: if SMS is high there is more chance of survival, this helps in patients immediate segregation of patients in casualty. Also conclude that FOUR score has a high degree of internal consistency & is an accurate predictor of Mortality and neurologic outcome in TBI patients. Keywords: Simplified Motor Score, Glasgow Coma Scale, Marshall CT, Rotterdam CT, FOUR scale.

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

Journal of International Medical Research ◽

10.1177/147323000703500509 ◽

2007 ◽

Vol 35 (5) ◽

pp. 644-656 ◽

Cited By ~ 12

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.

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Omega-3 polyunsaturated fatty acid attenuates the inflammatory response by modulating microglia polarization through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway following experimental traumatic brain injury

Journal of Neuroinflammation ◽

10.1186/s12974-018-1151-3 ◽

2018 ◽

Vol 15 (1) ◽

Cited By ~ 43

Author(s):

Xiangrong Chen ◽

Chunnuan Chen ◽

Sining Fan ◽

Shukai Wu ◽

Fuxing Yang ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Fatty Acid ◽

Brain Injury ◽

Inflammatory Response ◽

Polyunsaturated Fatty Acid ◽

Omega 3 ◽

Microglia Polarization ◽

Experimental Traumatic Brain Injury

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Abnormalities on Perfusion CT and Intervention for Intracranial Hypertension in Severe Traumatic Brain Injury

Journal of Clinical Medicine ◽

10.3390/jcm9062000 ◽

2020 ◽

Vol 9 (6) ◽

pp. 2000

Author(s):

Shannon Cooper ◽

Cino Bendinelli ◽

Andrew Bivard ◽

Mark Parsons ◽

Zsolt J. Balogh

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Intracranial Hypertension ◽

Severe Traumatic Brain Injury ◽

Injury Severity ◽

Intervention Group ◽

Small Sample ◽

Perfusion Computed Tomography ◽

Group I ◽

Second Tier

The role of invasive intracranial pressure (ICP) monitoring in patients with severe traumatic brain injury (STBI) remain unclear. Perfusion computed tomography (CTP) provides crucial information about the cerebral perfusion status in these patients. We hypothesised that CTP abnormalities would be associated with the severity of intracranial hypertension (ICH). To investigate this hypothesis, twenty-eight patients with STBI and ICP monitors were investigated with CTP within 48 h from admission. Treating teams were blind to these results. Patients were divided into five groups based on increasing intervention required to control ICH and were compared. Group I required no intervention above routine sedation, group II required a single first tier intervention, group III required multiple different first-tier interventions, group IV required second-tier medical therapy and group V required second-tier surgical therapy. Analysis of the results showed demographics and injury severity did not differ among groups. In group I no patients showed CTP abnormality, while patients in all other groups had abnormal CTP (p = 0.003). Severe ischaemia observed on CTP was associated with increasing intervention for ICH. This study, although limited by small sample size, suggests that CTP abnormalities are associated with the need to intervene for ICH. Larger scale assessment of our results is warranted to potentially avoid unnecessary invasive procedures in head injury patients.

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Fabrication of aortic bioprosthesis by decellularization, fibrin glue coating and re-endothelization: a cell scaffold approach

Progress in Biomaterials ◽

10.1007/s40204-019-00122-2 ◽

2019 ◽

Vol 8 (3) ◽

pp. 197-210 ◽

Cited By ~ 4

Author(s):

Sonal Walawalkar ◽

Shahdab Almelkar

Keyword(s):

Endothelial Cells ◽

Fibrin Glue ◽

Cellular Proliferation ◽

Graft Patency ◽

Cell Viability Assay ◽

Ethanol Group ◽

Viability Assay ◽

Group I ◽

Group Ii ◽

Cellular Dna

Abstract Aortic dysfunctions (aneurysm, aortitis) lead to the most serious conditions related to aortic wall with life-threatening complications. The most common modality of management for such conditions is replacement (diseased part) of aorta by a larger diameter stent (reconstructive vascular surgery) which in itself is a big trial. The most natural way is to use a re-endothelized scaffold. Developing a scaffold with biomimetic properties is an experimental aim for most of the scientists and surgeons. We aim to structure a strategy to overcome the well-known problems associated with aorta. In this study, we plan to remold a larger diameter blood vessel such as aorta from xenogeneic origin using different protocols to decellularize and comparing them with normal aorta. The chemicals and enzymes used for bovine aorta decellularization are 1% SDS (group II), 70% ethanol + 0.25% trypsin (group III), 70% ethanol (group IV), and 0.25% trypsin (group V). Group I served as control (without decellularization). Histology and SEM study were conducted for cellular presence/absence in all scaffolds. Later, the scaffolds were coated with the fibrin glue (FG) and endothelial cells were proliferated over them. 3D images were taken showing the remolding of the endothelial cells on FG-coated surfaces. The re-endothelization was confirmed by lectin and vWF+/+ expression. Graft elasticity and burst pressure were confirmed by biomechanical tensile testing. Further, the absence of host tissue DNA and presence of cellular DNA after re-endothelialization were confirmed by PicoGreen assay. The acceptability for metabolically active cellular proliferation on scaffolds and its non-toxicity were proved by cell viability assay. Current findings accomplish that larger diameter aorta extracellular matrix scaffold (group II) can be fabricated and re-endothelialized to develop non-thrombotic surfaces with improved graft patency with promising results compared to other fabricated scaffold groups.

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Annexin A2 Deficiency Exacerbates Neuroinflammation and Long-Term Neurological Deficits after Traumatic Brain Injury in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms20246125 ◽

2019 ◽

Vol 20 (24) ◽

pp. 6125 ◽

Cited By ~ 5

Author(s):

Ning Liu ◽

Yinghua Jiang ◽

Joon Yong Chung ◽

Yadan Li ◽

Zhanyang Yu ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Inflammatory Response ◽

Neurovascular Unit ◽

Annexin A2 ◽

Tissue Loss ◽

Neurological Deficits ◽

Endogenous Factors ◽

The Brain

Our laboratory and others previously showed that Annexin A2 knockout (A2KO) mice had impaired blood–brain barrier (BBB) development and elevated pro-inflammatory response in macrophages, implying that Annexin A2 (AnxA2) might be one of the key endogenous factors for maintaining homeostasis of the neurovascular unit in the brain. Traumatic brain injury (TBI) is an important cause of disability and mortality worldwide, and neurovascular inflammation plays an important role in the TBI pathophysiology. In the present study, we aimed to test the hypothesis that A2KO promotes pro-inflammatory response in the brain and worsens neurobehavioral outcomes after TBI. TBI was conducted by a controlled cortical impact (CCI) device in mice. Our experimental results showed AnxA2 expression was significantly up-regulated in response to TBI at day three post-TBI. We also found more production of pro-inflammatory cytokines in the A2KO mouse brain, while there was a significant increase of inflammatory adhesion molecules mRNA expression in isolated cerebral micro-vessels of A2KO mice compared with wild-type (WT) mice. Consistently, the A2KO mice brains had a significant increase in leukocyte brain infiltration at two days after TBI. Importantly, A2KO mice had significantly worse sensorimotor and cognitive function deficits up to 28 days after TBI and significantly larger brain tissue loss. Therefore, these results suggested that AnxA2 deficiency results in exacerbated early neurovascular pro-inflammation, which leads to a worse long-term neurologic outcome after TBI.

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Ibuprofen attenuates the inflammatory response and allows formation of migratory neuroblasts from grafted stem cells after traumatic brain injury

Restorative Neurology and Neuroscience ◽

10.3233/rnn-2011-0606 ◽

2012 ◽

Vol 30 (1) ◽

pp. 9-19 ◽

Cited By ~ 2

Author(s):

U. Wallenquist ◽

K. Holmqvist ◽

A. Hånell ◽

N. Marklund ◽

L. Hillered ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Stem Cells ◽

Brain Injury ◽

Inflammatory Response

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Severe Traumatic Brain Injury (TBI) Modulates the Kinetic Profile of the Inflammatory Response of Markers for Neuronal Damage

Journal of Clinical Medicine ◽

10.3390/jcm9061667 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1667 ◽

Cited By ~ 3

Author(s):

Cora Rebecca Schindler ◽

Thomas Lustenberger ◽

Mathias Woschek ◽

Philipp Störmann ◽

Dirk Henrich ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Inflammatory Response ◽

Calcium Binding ◽

Injury Severity ◽

Neuronal Damage ◽

Severe Trauma ◽

Multiple Injuries ◽

Kinetic Profile ◽

Severe Tbi

The inflammatory response plays an important role in the pathophysiology of multiple injuries. This study examines the effects of severe trauma and inflammatory response on markers of neuronal damage. A retrospective analysis of prospectively collected data in 445 trauma patients (Injury Severity Score (ISS) ≥ 16) is provided. Levels of neuronal biomarkers (calcium-binding Protein B (S100b), Enolase2 (NSE), glial fibrillary acidic protein (GFAP)) and Interleukins (IL-6, IL-10) in severely injured patients (with polytrauma (PT)) without traumatic brain injury (TBI) or with severe TBI (PT+TBI) and patients with isolated TBI (isTBI) were measured upon arrival until day 5. S100b, NSE, GFAP levels showed a time-dependent decrease in all cohorts. Their expression was higher after multiple injuries (p = 0.038) comparing isTBI. Positive correlation of marker level after concomitant TBI and isTBI (p = 0.001) was noted, while marker expression after PT appears to be independent. Highest levels of IL-6 and -10 were associated to PT und lowest to isTBI (p < 0.001). In all groups pro-inflammatory response (IL-6/-10 ratio) peaked on day 2 and at a lower level on day 4. Severe TBI modulates kinetic profile of inflammatory response by reducing interleukin expression following trauma. Potential markers for neuronal damage have a limited diagnostic value after severe trauma because undifferentiated increase.

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