Time-dependent changes of protein biomarker levels in the cerebrospinal fluid after blast traumatic brain injury

IntroductionThere is little systematic tracking or detailed analysis of investments in research and development for blast injury to support decision-making around research future funding.MethodsThis study examined global investments into blast injury-related research from public and philanthropic funders across 2000–2019. Research databases were searched using keywords, and open data were extracted from funder websites. Data collected included study title, abstract, award amount, funder and year. Individual awards were categorised to compare amounts invested into different blast injuries, the scientific approaches taken and analysis of research investment into blast traumatic brain injury (TBI).ResultsA total of 806 awards were identified into blast injury-related research globally, equating to US$902.1 million (m, £565.9m GBP). There was a general increase in year-on-year investment between 2003 and 2009 followed by a consistent decline in annual funding since 2010. Pre-clinical research received $671.3 m (74.4%) of investment. Brain-related injury research received $427.7 m (47.4%), orthopaedic injury $138.6 m (15.4%), eye injury $63.7 m (7.0%) and ear injury $60.5m (6.7%). Blast TBI research received a total investment of $384.3 m, representing 42.6% of all blast injury-related research. The U.S. Department of Defense funded $719.3 m (80%).ConclusionsInvestment data suggest that blast TBI research has received greater funding than other blast injury health areas. The funding pattern observed can be seen as reactive, driven by the response to the War on Terror, the rising profile of blast TBI and congressionally mandated research.

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Time-Dependent Changes in Microglia Transcriptional Networks Following Traumatic Brain Injury

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2019.00307 ◽

2019 ◽

Vol 13 ◽

Cited By ~ 9

Author(s):

Saef Izzy ◽

Qiong Liu ◽

Zhou Fang ◽

Sevda Lule ◽

Limin Wu ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Time Dependent ◽

Transcriptional Networks

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ELEVATION OF MATRIX METALLOPROTEINASES 3 AND 9 IN CEREBROSPINAL FLUID AND BLOOD IN PATIENTS WITH SEVERE TRAUMATIC BRAIN INJURY

Neurosurgery ◽

10.1227/01.neu.0000351768.11363.48 ◽

2009 ◽

Vol 65 (4) ◽

pp. 702-708 ◽

Cited By ~ 95

Author(s):

Mark Grossetete ◽

Jeremy Phelps ◽

Leopold Arko ◽

Howard Yonas ◽

Gary A. Rosenberg

Keyword(s):

Traumatic Brain Injury ◽

Cerebrospinal Fluid ◽

Brain Injury ◽

Matrix Metalloproteinases ◽

Blood Brain Barrier ◽

Normal Pressure Hydrocephalus ◽

Normal Pressure ◽

Brain Barrier ◽

Western Immunoblot ◽

Blood Brain

Abstract OBJECTIVE Traumatic brain injury (TBI) causes an increase in matrix metalloproteinases (MMPs), which are associated with neuroinflammation, blood-brain barrier disruption, hemorrhage, and cell death. We hypothesized that patients with TBI have an increase in MMPs in ventricular cerebrospinal fluid (CSF) and plasma. METHODS Patients with TBI and a ventricular catheter were entered into the study. Samples of CSF and plasma were collected at the time of catheter placement and at 24 and 72 hours after admission. Seven TBI patients were entered into the study, with 6 having complete data for analysis. Only patients who had a known time of insult that fell within a 6-hour window from initial insult to ventriculostomy were accepted into the study. Control CSF came from ventricular fluid in patients undergoing shunt placement for normal pressure hydrocephalus. Both MMP-2 and MMP-9 were measured with gelatin zymography and MMP-3 with Western immunoblot. RESULTS We found a significant elevation in the levels of the latent form of MMP-9 (92-kD) in the CSF obtained at the time of arrival (P < 0.05). Elevated levels of MMP-2 were detected in plasma at 72 hours, but not in the CSF. Using albumin from both CSF and blood, we calculated the MMP-9 index, which was significantly increased in the CSF, indicating endogenous MMP production. Western immunoblot showed elevated levels of MMP-3 in CSF at all times measured, whereas MMP-3 was not detected in the CSF of normal pressure hydrocephalus. CONCLUSION We show that MMPs are increased in the CSF of TBI patients. Although the number of patients was small, the results were robust and clearly demonstrated increases in MMP-3 and MMP-9 in ventricular CSF in TBI patients compared with controls. Although these preliminary results will need to be replicated, we propose that MMPs may be important in blood-brain barrier opening and hemorrhage secondary to brain injury in patients.

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P2-078: Neuroimaging and cerebrospinal fluid biomarkers in iraq and afghanistan veterans: Effects of deployment and blast concussion mild traumatic brain injury

Alzheimer s & Dementia ◽

10.1016/j.jalz.2015.06.615 ◽

2015 ◽

Vol 11 (7S_Part_11) ◽

pp. P513-P513

Author(s):

Elaine R. Peskind ◽

Eric C. Petrie ◽

Gail Li ◽

Donna Cross ◽

Vasily Yarnykh ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Cerebrospinal Fluid ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Cerebrospinal Fluid Biomarkers

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The Prognostic Significance of Biomarkers in Cerebrospinal Fluid Following Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis

SSRN Electronic Journal ◽

10.2139/ssrn.3941039 ◽

2021 ◽

Author(s):

Victor Schwartz Hvingelby ◽

Carsten Bjarkam ◽

Frantz Rom Poulsen ◽

Tiit Illimar Mathiesen ◽

Morten Thingemann Bøtker ◽

...

Keyword(s):

Systematic Review ◽

Traumatic Brain Injury ◽

Cerebrospinal Fluid ◽

Brain Injury ◽

Severe Traumatic Brain Injury ◽

Meta Analysis ◽

Prognostic Significance

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Severe Traumatic Brain Injury

10.2310/psych.2403 ◽

2018 ◽

Author(s):

Ryan Martin ◽

Lara Zimmermann ◽

Kee D. Kim ◽

Marike Zwienenberg ◽

Kiarash Shahlaie

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Intracranial Pressure ◽

Severe Traumatic Brain Injury ◽

Neurocritical Care ◽

Secondary Brain Injury ◽

Brain Oxygenation ◽

Barbiturate Coma ◽

Blast Traumatic Brain Injury ◽

Penetrating Traumatic Brain Injury

Traumatic brain injury remains a leading cause of death and disability worldwide. Patients with severe traumatic brain injury are best treated with a multidisciplinary, evidence-based, protocol-directed approach, which has been shown to decrease mortality and improve functional outcomes. Therapy is directed at the prevention of secondary brain injury through optimizing cerebral blood flow and the delivery of metabolic fuel (ie, oxygen and glucose). This is accomplished through the measurement and treatment of elevated intracranial pressure (ICP), the strict avoidance of hypotension and hypoxemia, and in some instances, surgical management. The treatment of elevated ICP is approached in a protocolized, tiered manner, with escalation of care occurring in the setting of refractory intracranial hypertension, culminating in either decompressive surgery or barbiturate coma. With such an approach, the rates of mortality secondary to traumatic brain injury are declining despite an increasing incidence of traumatic brain injury. This review contains 3 figures, 5 tables and 69 reference Key Words: blast traumatic brain injury, brain oxygenation, cerebral perfusion pressure, decompressive craniectomy, hyperosmolar therapy, intracranial pressure, neurocritical care, penetrating traumatic brain injury, severe traumatic brain injury

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