STUDY OF NEURON SPECIFIC ENOLASE (NSE) IN PERINATAL ASPHYXIA & ITS ROLE AS AN EARLY MARKER OF BRAIN INJURY

To explore the role of the interleukin (IL)-1β converting enzyme (ICE) in neuronal apoptosis, we designed a mutant ICE gene (C285G) that acts as a dominant negative ICE inhibitor. Microinjection of the mutant ICE gene into embryonal chicken dorsal root ganglial neurons inhibits trophic factor withdrawal–induced apoptosis. Transgenic mice expressing the fused mutant ICE-lacZ gene under the control of the neuron specific enolase promoter appeared neurologically normal. These mice are deficient in processing pro–IL-1β, indicating that mutant ICEC285G blocks ICE function. Dorsal root ganglial neurons isolated from transgenic mice were resistant to trophic factor withdrawal–induced apoptosis. In addition, the neurons isolated from newborn ICE knockout mice are similarly resistant to trophic factor withdrawal–induced apoptosis. After permanent focal ischemia by middle cerebral artery occlusion, the mutant ICEC285G transgenic mice show significantly reduced brain injury as well as less behavioral deficits when compared to the wild-type controls. Since ICE is the only enzyme with IL-1β convertase activity in mice, our data indicates that the mutant ICEC285G inhibits ICE, and hence mature IL-1β production, and through this mechanism, at least in part, inhibits apoptosis. Our data suggest that genetic manipulation using ICE family dominant negative inhibitors can ameliorate the extent of ischemia-induced brain injury and preserve neurological function.

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Correlation between brain injury biomarkers and Glasgow coma scale in pediatric sepsis

Paediatrica Indonesiana ◽

10.14238/pi52.2.2012.111-117 ◽

2012 ◽

Vol 52 (2) ◽

pp. 111

Author(s):

Nahari Arifin ◽

Irawan Mangunatmadja ◽

Antonius Pudjiadi ◽

Sudung O. Pardede

Keyword(s):

Brain Injury ◽

Analytical Study ◽

Brain Injuries ◽

Neuron Specific Enolase ◽

Maximum Level ◽

Inclusion Criteria ◽

Coma Scale ◽

Blood Specimens ◽

Pediatric Sepsis ◽

Increased Susceptibility

Background Sepsis in children, with or without multiple organfailure, causes increased susceptibility to brain injury due tosystemic insults. Brain injury in sepsis is difficult to recognizeclinically. Neuron-specific enolase (NSE) and S-lOOB have beenextensively studied in brain injuries and appear to be promisingalternative biomarkers.Objectives To determine if there is a correlation between theGlasgow coma scale (GCS) and NSE as well as S-lOOB levels, inchildren with sepsis.Methods We performed an analytical study on septic childrenaged > 2 years. GCS scores were assessed on the first and thirddays of admission. Blood specimens to test for NSE and S-lOOBwere drawn on the first day of admission and stored at -70QC forfurther analysis at the end of the study.Results Out of 35 patients, 30 met the inclusion criteria. Postanalysis,one subject with NSE above the maximum level wasexcluded. Negative correlations were found between GCS scoreand NSE, as well as between GCS and S-lOOB levels. Analysisrevealed a significant ROC for NSE, but not for S-lOOB. NSEconcentration of 8.1 /.lg/L was the cut-off point for GCS scoresbelow 12.Conclusions There were negative correlations between GCSand NSE levels, as well as between GCS and S- lOOB levels. Thepredictive value ofNSE level was a cut-off point of 8.1 /.lg/L forGCS scores below 12. [Paediatr lndones. 2012;52:111-17]

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Predictive value of neuron-specific enolase following moderate and severe traumatic brain injury: a systematic review and meta-analysis

Critical Care ◽

10.1186/cc10918 ◽

2012 ◽

Vol 16 (S1) ◽

Author(s):

E Mercier ◽

AF Turgeon ◽

A Boutin ◽

F Lauzier ◽

R Zarychanski ◽

...

Keyword(s):

Systematic Review ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Severe Traumatic Brain Injury ◽

Predictive Value ◽

Meta Analysis ◽

Neuron Specific Enolase

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Nanotherapeutic modulation of excitotoxicity and oxidative stress in acute brain injury

Nanobiomedicine ◽

10.1177/1849543520970819 ◽

2020 ◽

Vol 7 ◽

pp. 184954352097081

Author(s):

Rick Liao ◽

Thomas R Wood ◽

Elizabeth Nance

Keyword(s):

Oxidative Stress ◽

Brain Injury ◽

Calcium Influx ◽

Perinatal Asphyxia ◽

Pathological Process ◽

Global Brain Ischemia ◽

Excitatory Neurotransmitters ◽

Disease Site ◽

The Right ◽

Global Brain

Excitotoxicity is a primary pathological process that occurs during stroke, traumatic brain injury (TBI), and global brain ischemia such as perinatal asphyxia. Excitotoxicity is triggered by an overabundance of excitatory neurotransmitters within the synapse, causing a detrimental cascade of excessive sodium and calcium influx, generation of reactive oxygen species, mitochondrial damage, and ultimately cell death. There are multiple potential points of intervention to combat excitotoxicity and downstream oxidative stress, yet there are currently no therapeutics clinically approved for this specific purpose. For a therapeutic to be effective against excitotoxicity, the therapeutic must accumulate at the disease site at the appropriate concentration at the right time. Nanotechnology can provide benefits for therapeutic delivery, including overcoming physiological obstacles such as the blood–brain barrier, protect cargo from degradation, and provide controlled release of a drug. This review evaluates the use of nano-based therapeutics to combat excitotoxicity in stroke, TBI, and hypoxia–ischemia with an emphasis on mitigating oxidative stress, and consideration of the path forward toward clinical translation.

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LO86: Lack of association between four biomarkers and the presence of persistent post-concussion symptoms after a mild traumatic brain injury

CJEM ◽

10.1017/cem.2020.140 ◽

2020 ◽

Vol 22 (S1) ◽

pp. S38-S39

Author(s):

N. Le Sage ◽

J. Frenette ◽

J. Chauny ◽

S. Berthelot ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Clinical Data ◽

Neuron Specific Enolase ◽

Primary Outcome Measure ◽

S100b Protein ◽

Future Research ◽

Enzyme Linked Immunosorbent Assay ◽

Persistent Symptoms

Introduction: Mild Traumatic Brain Injury (mTBI) is a common problem: each year in Canada, its incidence is estimated at 500-600 cases per 100 000. Between 10 and 56% of mTBI patients develop persistent post-concussion symptoms (PPCS) that can last for more than 90 days. It is therefore important for clinicians to identify patients who are at risk of developing PPCS. We hypothesized that blood biomarkers drawn upon patient arrival to the Emergency Department (ED) could help predict PPCS. The main objective of this project was to measure the association between four biomarkers and the incidence of PPCS 90 days post mTBI. Methods: Patients were recruited in seven Canadian ED. Non-hospitalized patients, aged ≥14 years old with a documented mTBI that occurred ≤24 hrs of ED consultation, with a GCS ≥13 at arrival were included. Sociodemographic and clinical data as well as blood samples were collected in the ED. A standardized telephone questionnaire was administered at 90 days post ED visit. The following biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA): S100B protein, Neuron Specific Enolase (NSE), cleaved-Tau (c-Tau) and Glial fibrillary acidic protein (GFAP). The primary outcome measure was the presence of persistent symptoms at 90 days after mTBI, as assessed using the Rivermead Post-Concussion symptoms Questionnaire (RPQ). A ROC curve was constructed for each biomarker. Results: 1276 patients were included in the study. The median age for this cohort was 39 (IQR 23-57) years old, 61% were male and 15% suffered PPCS. The median values (IQR) for patients with PPCS compared to those without were: 43 pg/mL (26-67) versus 42 pg/mL (24-70) for S100B protein, 50 pg/mL (50-223) versus 50 pg/mL (50-199) for NSE, 2929 pg/mL (1733-4744) versus 3180 pg/mL (1835-4761) for c-Tau and 1644 pg/mL (650-3215) versus 1894 pg/mL (700-3498) for GFAP. For each of these biomarkers, Areas Under the Curve (AUC) were 0.495, 0.495, 0.51 and 0.54, respectively. Conclusion: Among mTBI patients, S100B protein, NSE, c-Tau or GFAP during the first 24 hours after trauma do not seem to be able to predict PPCS. Future research testing of other biomarkers is needed in order to determine their usefulness in predicting PPCS when combined with relevant clinical data.

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