Biomarkers for the Diagnosis, Prognosis, and Evaluation of Treatment Efficacy for Traumatic Brain Injury

Dash, Pramod K.; Zhao, Jing; Hergenroeder, Georgene W.; Moore, Anthony N.

doi:10.1016/j.nurt.2009.10.019

Cited by 177 publications

(141 citation statements)

References 151 publications

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“…CSF and serum levels of these markers have been shown to increase after moderate-tosevere TBI, presumably as a result of tissue damage and their release into the circulating fluid. 54,55 We examined whether or not the tissue level of GFAP and UCHL1 were affected by mild TBI. Our findings, illustrated in Figure 9, showed that there was a delayed increase in cortical tissue GFAP after mFPI, consistent with reports of elevated GFAP after a diffuse mild injury.…”

Section: Mtbi Pathway Analysismentioning

confidence: 99%

Analysis of Functional Pathways Altered after Mild Traumatic Brain Injury

Redell

Moore

Grill

et al. 2013

Journal of Neurotrauma

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Concussive injury (or mild traumatic brain injury; mTBI) can exhibit features of focal or diffuse injury patterns. We compared and contrasted the cellular and molecular responses after mild controlled cortical impact (mCCI; a focal injury) or fluid percussion injury (FPI; a diffuse injury) in rats. The rationale for this comparative analysis was to investigate the brain's response to mild diffuse versus mild focal injury to identify common molecular changes triggered by these injury modalities and to determine the functional pathways altered after injury that may provide novel targets for therapeutic intervention. Microarrays containing probes against 21,792 unique messenger RNAs (mRNAs) were used to investigate the changes in cortical mRNA expression levels at 3 and 24 h postinjury. Of the 354 mRNAs with significantly altered expression levels after mCCI, over 89% (316 mRNAs) were also contained within the mild FPI (mFPI) data set. However, mFPI initiated a more widespread molecular response, with over 2300 mRNAs differentially expressed. Bioinformatic analysis of annotated Gene Ontology molecular function and biological pathway terms showed a significant overrepresentation of genes belonging to inflammation, stress, and signaling categories in both data sets. We therefore examined changes in the protein levels of a panel of 23 cytokines and chemokines in cortical extracts using a Luminex-based bead immunoassay and detected significant increases in macrophage inflammatory protein (MIP)-1a (CCL3), GRO-KC (CXCL1), interleukin (IL)-1a, IL-1b, and IL-6. Immunohistochemical localization of MIP-1a and IL-1b showed marked increases at 3 h postinjury in the cortical vasculature and microglia, respectively, that were largely resolved by 24 h postinjury. Our findings demonstrate that both focal and diffuse mTBI trigger many shared pathobiological processes (e.g., inflammatory responses) that could be targeted for mechanism-based therapeutic interventions.

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Section: Mtbi Pathway Analysismentioning

confidence: 99%

Analysis of Functional Pathways Altered after Mild Traumatic Brain Injury

Redell

Moore

Grill

et al. 2013

Journal of Neurotrauma

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“…Also, studies available on candidate biomarkers that can possibly be used to diagnose TBI and predict post-injury functional outcome provide no information on whether the TBI biomarkers could be used as PTE biomarkers [61,62].…”

Section: Biomarkers For Epileptogenesis After Brain Injurymentioning

confidence: 99%

Epilepsy Related to Traumatic Brain Injury

2014

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Post-traumatic epilepsy accounts for 10-20 % of symptomatic epilepsy in the general population and 5 % of all epilepsy. During the last decade, an increasing number of laboratories have investigated the molecular and cellular mechanisms of post-traumatic epileptogenesis in experimental models. However, identification of critical molecular, cellular, and network mechanisms that would be specific for posttraumatic epileptogenesis remains a challenge. Despite of that, 7 of 9 proof-of-concept antiepileptogenesis studies have demonstrated some effect on seizure susceptibility after experimental traumatic brain injury, even though none of them has progressed to clinic. Moreover, there has been some promise that new clinically translatable imaging approaches can identify biomarkers for post-traumatic epileptogenesis. Even though the progress in combating post-traumatic epileptogenesis happens in small steps, recent discoveries kindle hope for identification of treatment strategies to prevent post-traumatic epilepsy in at-risk patients.

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“…Despite there being a number of biomarkers that have been shown to correlate with injury magnitude and survivability (5,13), there are few reliable methods to predict the clinical outcomes for TBI patients; therefore, there is a desperate need to identify more specific and sensitive biomarkers to serve as parameters for TBI management and prognosis.…”

Section: Travmatik Beyin Hasarının Prognozuyla Ventriküler Beyin Omurmentioning

confidence: 99%

Matrix metalloproteinase-9 in the ventricular cerebrospinal ﬂuid correlated with the prognosis of traumatic brain injury

Liu¹,

Chen²,

Lee³

et al. 2013

Turkish Neurosurgery

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AIm: Matrix metalloproteinase 9 (MMP-9) has been shown to be a potential biomarker for outcome prediction after neuron damage. This study investigated whether MMP-9 could be used for outcome prediction after traumatic brain injury (TBI). mATERIAL and mETHods: For the TBI group, cerebrospinal fluid (CSF) was collected at different days after surgery from 6 head injury patients who had received surgical intervention with external ventricular drainage insertion. CSF collected from non-TBI patients (N=85) diagnosed with isolated hydrocephalus by a ventricular puncture during a ventriculo-peritoneal shunt surgery was used as control. REsuLTs:The mean concentration of MMP-9 in the CSF of 85 non-TBI patients was determined to be 1.172±0.859 ng/mL. We found that the CSF MMP-9 concentration from TBI patients was elevated immediately after head injury with a median of 1.926 ng/mL (range, 0.673 to 24.990). Despite an early increase in the concentration of MMP-9, levels decreased within 72 hrs and nearly reached the normal range. Nevertheless, the concentration of MMP-9 was negatively correlated with the Glasgow Coma Scale (γ = -0.337, p = 0.013).CoNCLusIoN: MMP-9 concentration in the CSF of TBI patients correlated with neurological outcome and may represent an early indicator for the prognosis of this condition. KEywoRds:Cerebrospinal fluid, Biomarker, Matrix metalloproteinase-9, Traumatic brain injury, Glasgow Coma Scale ÖZ AmAÇ: Matriks metalloproteinaz 9'un (MMP-9) nöron hasarından sonra sonuçların tahmin edilmesinde olası bir biyobelirteç olduğu gösterilmiştir. Bu çalışma, MMP-9'un travmatik beyin hasarından sonra sonucu öngörmek için kullanılıp, kullanılamayacağını incelemiştir. yÖNTEm ve GEREÇLER: Travmatik beyin hasarı grubunda eksternal ventriküler drenaj yerleştirilmesiyle cerrahi girişim yapılmış 6 kafa travması hastasında cerrahi sonrasında farklı günlerde beyin omurilik sıvısı (BOS) toplanmıştır. Kontrol olarak bir ventriküloperitoneal şant cerrahisi sırasında ventriküler ponksiyon ile izole hidrosefali tanısı konmuş, travmatik beyin hasarı olmayan hastalardan BOS toplanmıştır (N=85).BuLGuLAR: Travmatik beyin hasarı olmayan 85 hastanın BOS'unda ortalama MMP-9 konsantrasyonunun 1,172±0,859 ng/mL olduğu bulunmuştur. Travmatik beyin hasarı hastalarında BOS MMP-9 konsantrasyonunun kafa travmasından hemen sonra medyan 1,926 ng/mL (aralık, 0,673 -24,990) değeriyle yükseldiğini bulduk. MMP-9 konsantrasyonunda erken bir artışa rağmen seviyeler 72 saat içinde azaldı ve hemen hemen normal aralığa döndü. Yine de MMP-9 konsantrasyonu Glasgow Koma Skalası ile negatif korelasyon gösterdi (γ = -0,337, p = 0,013).soNuÇ: MMP-9 konsantrasyonu travmatik beyin hasarlı hastaların BOS'unda nörolojik sonuçla korelasyon gösterdi ve böylece prognoz için erken bir gösterge olabileceği düşünüldü.ANAHTAR sÖZCÜKLER: Beyin omurilik sıvısı, Biyobelirteç, Matriks metalloproteinaz-9, Travmatik beyin hasarı, Glasgow Koma Skalası

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Biomarkers for the Diagnosis, Prognosis, and Evaluation of Treatment Efficacy for Traumatic Brain Injury

Cited by 177 publications

References 151 publications

Analysis of Functional Pathways Altered after Mild Traumatic Brain Injury

Analysis of Functional Pathways Altered after Mild Traumatic Brain Injury

Epilepsy Related to Traumatic Brain Injury

Matrix metalloproteinase-9 in the ventricular cerebrospinal ﬂuid correlated with the prognosis of traumatic brain injury

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Biomarkers for the Diagnosis, Prognosis, and Evaluation of Treatment Efficacy for Traumatic Brain Injury

Cited by 177 publications

References 151 publications

Analysis of Functional Pathways Altered after Mild Traumatic Brain Injury

Analysis of Functional Pathways Altered after Mild Traumatic Brain Injury

Epilepsy Related to Traumatic Brain Injury

Matrix metalloproteinase-9 in the ventricular cerebrospinal &#64258;uid correlated with the prognosis of traumatic brain injury

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Matrix metalloproteinase-9 in the ventricular cerebrospinal ﬂuid correlated with the prognosis of traumatic brain injury