Systemic Inflammation Alters the Neuroinflammatory Response: A Prospective Clinical Trial in Traumatic Brain Injury.

Abstract Background: Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development, however how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition.Methods: TBI patients recruited to a previous randomized controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n=10 treatment arm, n=10 control arm). Cytokine concentrations were measured in arterial and venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 hours. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used.Results: The development of a systemic clinical infection results in an altered brain-ECF cytokine response (e.g. increase in G-CSF and decrease in PDGF-ABBB, p<0.05 respectively), even if adjusting for injury severity and demographic factors. rhIL1ra administration had a strong effect on the inflammatory response, independently altering different blood (n=6) and brain cytokine (n=3) levels. No substantial delayed temporal association between blood and brain compartments could be detected. Jugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen.Conclusions: Systemic inflammation, and infection in particular, alters cerebral cytokine levels, and rhIL1ra administration potently affects both systemic and cerebral cytokine levels. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, and stresses the need of adequate monitoring of inflammatory markers.

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Systemic inflammation alters the neuroinflammatory response: a prospective clinical trial in traumatic brain injury

Journal of Neuroinflammation ◽

10.1186/s12974-021-02264-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Philipp Lassarén ◽

Caroline Lindblad ◽

Arvid Frostell ◽

Keri L. H. Carpenter ◽

Mathew R. Guilfoyle ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Information Content ◽

Systemic Inflammation ◽

Injury Severity ◽

Extracellular Fluid ◽

Clinical Infection ◽

Mixed Effect ◽

Markers Of Inflammation ◽

Arterial Blood

Abstract Background Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development; however, how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition. Methods TBI patients recruited to a previous randomised controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n = 10 treatment arm, n = 10 control arm). Cytokine concentrations were measured in arterial and jugular venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 h. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used. Results Jugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen. No substantial delayed temporal associations between blood and brain compartments were detected. The development of a systemic clinical infection resulted in a significant decrease of IL1-ra, G-CSF, PDGF-ABBB, MIP-1b and RANTES (p < 0.05, respectively) in brain-ECF, even if adjusting for injury severity and demographic factors, while an increase in several cytokines could be seen in arterial blood. Conclusions Systemic inflammation, and infection in particular, alters cytokine levels with different patterns seen in brain and in blood. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, but novel prospective trials are warranted to confirm these associations. Graphical abstract

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Systemic Inflammation Alters The Neuroinflammatory Response: A Prospective Clinical Trial In Traumatic Brain Injury

10.21203/rs.3.rs-345717/v2 ◽

2021 ◽

Author(s):

Philipp Lassarén ◽

Caroline Lindblad ◽

Arvid Frostell ◽

Keri LH Carpenter ◽

Mathew R Guilfoyle ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Information Content ◽

Systemic Inflammation ◽

Injury Severity ◽

Extracellular Fluid ◽

Clinical Infection ◽

Mixed Effect ◽

Markers Of Inflammation ◽

Arterial Blood

Abstract Background: Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development, however how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition.Methods: TBI patients recruited to a previous randomized controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n=10 treatment arm, n=10 control arm). Cytokine concentrations were measured in arterial and jugular venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 hours. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used.Results: Jugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen. No substantial delayed temporal associations between blood and brain compartments were detected. The development of a systemic clinical infection resulted in a significant decrease of IL1-ra, G-CSF, PDGF-ABBB, MIP-1b and RANTES (p<0.05, respectively) in brain-ECF, even if adjusting for injury severity and demographic factors, while an increase in several cytokines could be seen in arterial blood. Conclusions: Systemic inflammation, and infection in particular, alters cytokine levels with different patterns seen in brain and in blood. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, and stresses the need of adequate monitoring of inflammatory markers.

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Cerebral Vascular and Metabolic Response to Sustained Systemic Inflammation in Ovine Traumatic Brain Injury

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/01.wcb.0000141516.61418.82 ◽

2004 ◽

Vol 24 (12) ◽

pp. 1400-1408 ◽

Cited By ~ 6

Author(s):

Henning D. Stubbe ◽

Christoph Greiner ◽

Hugo Van Aken ◽

Christian H. Rickert ◽

Martin Westphal ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Intracranial Pressure ◽

Inflammatory Response ◽

Systemic Inflammation ◽

Metabolic Response ◽

Cerebral Vasodilation ◽

Global Brain ◽

The Impact ◽

Cerebral Vascular

Traumatic brain injury (TBI) is frequently accompanied by a systemic inflammatory response secondary to multiple trauma, shock, or infections. This study investigated the impact of sustained systemic inflammation on cerebral hemodynamics and metabolism in ovine traumatic brain injury. Fifteen sheep were investigated for 14 hours. Head injury was induced with a nonpenetrating stunner in anesthetized, ventilated animals. One group (TBI/Endo, n = 6) subsequently received a continuous endotoxin infusion for 12 hours, whereas a second group (TBI, n = 6) received the carrier. Three instrumented animals served as sham controls. Head impact significantly increased intracranial pressure from 9 ± 4 mm Hg to 21 ± 15 mm Hg (TBI/Endo) and from 10 ± 3 mm Hg to 24 ± 19 mm Hg (TBI) (means ± SD). Internal carotid blood flow increased and cerebral vascular resistance decreased ( P < 0.05) during the hyperdynamic inflammatory response between 10 and 14 hours in the TBI/Endo group, whereas these parameters were at baseline level in the TBI group. Intracranial pressure remained unchanged during this period, but increased during hypercapnia. The CMRO2, PaCO2, and arterial hematocrit values were identical among the groups between 10 and 14 hours. It is concluded that chronic endotoxemia in ovine traumatic brain injury was associated with cerebral vasodilation uncoupled from global brain metabolism. Different mechanisms appear to induce cerebral vasodilation in response to inflammation and hypercapnia.

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Artifact removal from neurophysiological signals: impact on intracranial and arterial pressure monitoring in traumatic brain injury

Journal of Neurosurgery ◽

10.3171/2019.2.jns182260 ◽

2020 ◽

Vol 132 (6) ◽

pp. 1952-1960 ◽

Cited By ~ 1

Author(s):

Seung-Bo Lee ◽

Hakseung Kim ◽

Young-Tak Kim ◽

Frederick A. Zeiler ◽

Peter Smielewski ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neurological Status ◽

Cerebrovascular Reactivity ◽

Cerebral Hypoperfusion ◽

Clinical Parameters ◽

Artifact Removal ◽

Clinical Events ◽

Arterial Blood ◽

Before And After

OBJECTIVEMonitoring intracranial and arterial blood pressure (ICP and ABP, respectively) provides crucial information regarding the neurological status of patients with traumatic brain injury (TBI). However, these signals are often heavily affected by artifacts, which may significantly reduce the reliability of the clinical determinations derived from the signals. The goal of this work was to eliminate signal artifacts from continuous ICP and ABP monitoring via deep learning techniques and to assess the changes in the prognostic capacities of clinical parameters after artifact elimination.METHODSThe first 24 hours of monitoring ICP and ABP in a total of 309 patients with TBI was retrospectively analyzed. An artifact elimination model for ICP and ABP was constructed via a stacked convolutional autoencoder (SCAE) and convolutional neural network (CNN) with 10-fold cross-validation tests. The prevalence and prognostic capacity of ICP- and ABP-related clinical events were compared before and after artifact elimination.RESULTSThe proposed SCAE-CNN model exhibited reliable accuracy in eliminating ABP and ICP artifacts (net prediction rates of 97% and 94%, respectively). The prevalence of ICP- and ABP-related clinical events (i.e., systemic hypotension, intracranial hypertension, cerebral hypoperfusion, and poor cerebrovascular reactivity) all decreased significantly after artifact removal.CONCLUSIONSThe SCAE-CNN model can be reliably used to eliminate artifacts, which significantly improves the reliability and efficacy of ICP- and ABP-derived clinical parameters for prognostic determinations after TBI.

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Faculty Opinions recommendation of Differential influence of arterial blood glucose on cerebral metabolism following severe traumatic brain injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1158503.618678 ◽

2009 ◽

Author(s):

Arun Gupta

Keyword(s):

Traumatic Brain Injury ◽

Blood Glucose ◽

Brain Injury ◽

Severe Traumatic Brain Injury ◽

Cerebral Metabolism ◽

Arterial Blood ◽

Arterial Blood Glucose

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Altered speech patterns in subjects with post-traumatic headache due to mild traumatic brain injury

The Journal of Headache and Pain ◽

10.1186/s10194-021-01296-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Catherine D. Chong ◽

Jianwei Zhang ◽

Jing Li ◽

Teresa Wu ◽

Gina Dumkrieger ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Speech Production ◽

Mild Traumatic Brain Injury ◽

Mobile Application ◽

Speaking Rate ◽

Mixed Effect ◽

Effect Model ◽

Vowel Space ◽

Post Traumatic

Abstract Background/objective Changes in speech can be detected objectively before and during migraine attacks. The goal of this study was to interrogate whether speech changes can be detected in subjects with post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) and whether there are within-subject changes in speech during headaches compared to the headache-free state. Methods Using a series of speech elicitation tasks uploaded via a mobile application, PTH subjects and healthy controls (HC) provided speech samples once every 3 days, over a period of 12 weeks. The following speech parameters were assessed: vowel space area, vowel articulation precision, consonant articulation precision, average pitch, pitch variance, speaking rate and pause rate. Speech samples of subjects with PTH were compared to HC. To assess speech changes associated with PTH, speech samples of subjects during headache were compared to speech samples when subjects were headache-free. All analyses were conducted using a mixed-effect model design. Results Longitudinal speech samples were collected from nineteen subjects with PTH (mean age = 42.5, SD = 13.7) who were an average of 14 days (SD = 32.2) from their mTBI at the time of enrollment and thirty-one HC (mean age = 38.7, SD = 12.5). Regardless of headache presence or absence, PTH subjects had longer pause rates and reductions in vowel and consonant articulation precision relative to HC. On days when speech was collected during a headache, there were longer pause rates, slower sentence speaking rates and less precise consonant articulation compared to the speech production of HC. During headache, PTH subjects had slower speaking rates yet more precise vowel articulation compared to when they were headache-free. Conclusions Compared to HC, subjects with acute PTH demonstrate altered speech as measured by objective features of speech production. For individuals with PTH, speech production may have been more effortful resulting in slower speaking rates and more precise vowel articulation during headache vs. when they were headache-free, suggesting that speech alterations were related to PTH and not solely due to the underlying mTBI.

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217 The end-tidal and arterial carbon dioxide gradient in serious traumatic brain injury after pre-hospital emergency anaesthesia: a retrospective observational study

Emergency Medicine Journal ◽

10.1136/emj-2020-rcemabstracts.43 ◽

2020 ◽

Vol 37 (12) ◽

pp. 847.1-847

Author(s):

James Price ◽

Daniel Sandbach ◽

Ari Ercole ◽

Alastair Wilson ◽

Ed Barnard

Keyword(s):

Carbon Dioxide ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Thoracic Injury ◽

Secondary Brain Injury ◽

Hospital Emergency ◽

Hospital Arrival ◽

Arterial Blood ◽

End Tidal ◽

Emergency Anaesthesia

Aims/Objectives/BackgroundIn the United Kingdom (UK), 20% of patients with severe traumatic brain injury (TBI) receive pre-hospital emergency anaesthesia (PHEA). Current guidance recommends an end-tidal carbon dioxide (ETCO2) of 4.0–4.5kPa to achieve a low-normal arterial partial pressure of CO2 (PaCO2), and reduce secondary brain injury. This recommendation assumes a 0.5kPa ETCO2-PaCO2 gradient. However, the gradient in the acute phase of TBI is unknown. Our primary aim was to report the ETCO2-PaCO2 gradient of TBI patients at hospital arrival.Methods/DesignA retrospective cohort study of adult patients with serious TBI, who received a PHEA by a pre-hospital critical care team in the East of England between 1st April 2015 to 31st December 2017. Linear regression was performed to test for correlation and reported as R-squared (R2). A Bland-Altman plot was used to test for paired ETCO2 and PaCO2 agreement and reported with 95% confidence intervals (95%CI). ETCO2-PaCO2 gradient data were compared with a two-tailed, unpaired, t-test.Results/Conclusions107 patients were eligible for inclusion. Sixty-seven patients did not receive a PaCO2 sample within 30 minutes of hospital arrival and were therefore excluded. Forty patients had complete data and were included in the final analysis; per protocol.The mean ETCO2-PaCO2 gradient was 1.7 (±1.0) kPa, with only moderate correlation of ETCO2 and PaCO2 at hospital arrival (R2=0.23, p=0.002). The Bland-Altman bias was 1.7 (95%CI 1.4–2.0) kPa with upper and lower limits of agreement of 3.6 (95%CI 3.0–4.1) kPa and -0.2 (95%CI -0.8–0.3) kPa respectively. There was no significant gradient correlation in patients with a co-existing serious thoracic injury (R2=0.13, p=0.10), and this cohort had a larger ETCO2-PaCO2 gradient, 2.0 (±1.1) kPa, p=0.01. Patients who underwent pre-hospital arterial blood sampling had an arrival PaCO2 of 4.7 (±0.2) kPa.Lower ETCO2 targets than previously recommended may be safe and appropriate. The use of pre-hospital PaCO2 measurement is advocated.

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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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