scholarly journals Elevated serum miR-93, miR-191, and miR-499 are noninvasive biomarkers for the presence and progression of traumatic brain injury

2016 ◽  
Vol 137 (1) ◽  
pp. 122-129 ◽  
Author(s):  
Ting Yang ◽  
Jiaxi Song ◽  
Xiaomin Bu ◽  
Cheng Wang ◽  
Jia Wu ◽  
...  
2016 ◽  
Vol 17 (6) ◽  
pp. 739-755 ◽  
Author(s):  
Shenandoah Robinson ◽  
Jesse L. Winer ◽  
Justin Berkner ◽  
Lindsay A. S. Chan ◽  
Jesse L. Denson ◽  
...  

OBJECTIVE Traumatic brain injury (TBI) is a leading cause of death and severe morbidity for otherwise healthy full-term infants around the world. Currently, the primary treatment for infant TBI is supportive, as no targeted therapies exist to actively promote recovery. The developing infant brain, in particular, has a unique response to injury and the potential for repair, both of which vary with maturation. Targeted interventions and objective measures of therapeutic efficacy are needed in this special population. The authors hypothesized that MRI and serum biomarkers can be used to quantify outcomes following infantile TBI in a preclinical rat model and that the potential efficacy of the neuro-reparative agent erythropoietin (EPO) in promoting recovery can be tested using these biomarkers as surrogates for functional outcomes. METHODS With institutional approval, a controlled cortical impact (CCI) was delivered to postnatal Day (P)12 rats of both sexes (76 rats). On postinjury Day (PID)1, the 49 CCI rats designated for chronic studies were randomized to EPO (3000 U/kg/dose, CCI-EPO, 24 rats) or vehicle (CCI-veh, 25 rats) administered intraperitoneally on PID1–4, 6, and 8. Acute injury (PID3) was evaluated with an immunoassay of injured cortex and serum, and chronic injury (PID13–28) was evaluated with digitized gait analyses, MRI, and serum immunoassay. The CCI-veh and CCI-EPO rats were compared with shams (49 rats) primarily using 2-way ANOVA with Bonferroni post hoc correction. RESULTS Following CCI, there was 4.8% mortality and 55% of injured rats exhibited convulsions. Of the injured rats designated for chronic analyses, 8.1% developed leptomeningeal cyst–like lesions verified with MRI and were excluded from further study. On PID3, Western blot showed that EPO receptor expression was increased in the injured cortex (p = 0.008). These Western blots also showed elevated ipsilateral cortex calpain degradation products for αII-spectrin (αII-SDPs; p < 0.001), potassium chloride cotransporter 2 (KCC2-DPs; p = 0.037), and glial fibrillary acidic protein (GFAP-DPs; p = 0.002), as well as serum GFAP (serum GFAP-DPs; p = 0.001). In injured rats multiplex electrochemiluminescence analyses on PID3 revealed elevated serum tumor necrosis factor alpha (TNFα p = 0.01) and chemokine (CXC) ligand 1 (CXCL1). Chronically, that is, in PID13–16 CCI-veh rats, as compared with sham rats, gait deficits were demonstrated (p = 0.033) but then were reversed (p = 0.022) with EPO treatment. Diffusion tensor MRI of the ipsilateral and contralateral cortex and white matter in PID16–23 CCI-veh rats showed widespread injury and significant abnormalities of functional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD); MD, AD, and RD improved after EPO treatment. Chronically, P13–P28 CCI-veh rats also had elevated serum CXCL1 levels, which normalized in CCI-EPO rats. CONCLUSIONS Efficient translation of emerging neuro-reparative interventions dictates the use of age-appropriate preclinical models with human clinical trial–compatible biomarkers. In the present study, the authors showed that CCI produced chronic gait deficits in P12 rats that resolved with EPO treatment and that chronic imaging and serum biomarkers correlated with this improvement.


2021 ◽  
Vol 16 ◽  
pp. 117727192110534
Author(s):  
Ker Rui Wong ◽  
William T O’Brien ◽  
Mujun Sun ◽  
Glenn Yamakawa ◽  
Terence J O’Brien ◽  
...  

Introduction: Serum neurofilament light (NfL) is an emerging biomarker of traumatic brain injury (TBI). However, the effect of peripheral injuries such as long bone fracture and skeletal muscle injury on serum NfL levels is unknown. Therefore, the aim of this study was to determine whether serum NfL levels can be used as a biomarker of TBI in the presence of concomitant peripheral injuries. Methods: Rats were randomly assigned to one of four injury groups: polytrauma (muscle crush + fracture + TBI; n = 11); peripheral injuries (muscle crush + fracture + sham-TBI; n = 12); TBI-only (sham-muscle crush + sham-fracture + TBI; n = 13); and triple-sham (n = 7). At 2-days post-injury, serum levels of NfL were quantified using a Simoa HD-X Analyzer. Results: Compared to triple-sham rats, serum NfL concentrations were higher in rats with peripheral injuries-only, TBI-only, and polytrauma. When compared to peripheral injury-only rats, serum NfL levels were higher in TBI-only and polytrauma rats. No differences were found between TBI-only and polytrauma rats. Conclusion: Serum NfL levels did not differ between TBI-only and polytrauma rats, indicating that significant peripheral injuries did not affect the sensitivity and specificity of serum NfL as a biomarker of moderate TBI. However, the finding of elevated serum NfL levels in rats with peripheral injuries in the absence of a TBI suggests that the presence of such injuries may limit the utility of NfL as a biomarker of less severe TBI (eg, concussion).


2020 ◽  
Vol 48 (5) ◽  
pp. 030006052092245
Author(s):  
Yu-rong Wang ◽  
Qing-bin Zheng ◽  
Guang-fa Wei ◽  
Li-jun Meng ◽  
Qing-ling Feng ◽  
...  

Purpose Disease severity and inflammatory response status are closely related to a poor prognosis and must be assessed in patients with severe traumatic brain injury (STBI) before intensive care unit (ICU) discharge. Whether elevated serum procalcitonin (PCT) levels can predict a poor prognosis in STBI patients before ICU discharge is unclear. Methods This retrospective observational cohort study enrolled 199 STBI patients who were in the ICU for at least 48 hours and survived after discharge. Based on serum PCT levels at discharge, patients were divided into the high-PCT group (PCT ≥ 0.25 ng/mL) and the low-PCT group (PCT < 0.25 ng/mL). We assessed the relationship between serum PCT levels and a poor prognosis. Results The high-PCT group had a higher rate of adverse outcomes compared with the low-PCT group. Multivariate logistic regression analysis showed that the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, white blood cell (WBC) count, C-reactive protein (CRP) level, and PCT level at discharge were significantly associated with adverse outcomes. Conclusions Elevated PCT levels at ICU discharge were associated with a poor prognosis in STBI patients. The serum PCT level as a single indicator has limited value for clinical decision-making.


2017 ◽  
Vol 36 (4) ◽  
pp. 314-321 ◽  
Author(s):  
Branislava Stefanović ◽  
Olivera Đurić ◽  
Sanja Stanković ◽  
Srđan Mijatović ◽  
Krstina Doklestić ◽  
...  

SummaryBackground: The objective of our study was to determine the serum concentrations of protein S100B and neuron specific enolase (NSE) as well as their ability and accuracy in the prediction of early neurological outcome after a traumatic brain injury. Methods: A total of 130 polytraumatized patients with the associated traumatic brain injuries were included in this prospective cohort study. Serum protein S100B and NSE levels were measured at 6, 24, 48 and 72 hours after the injury. Early neurological outcome was scored by Glasgow Outcome Scale (GOS) on day 14 after the brain injury. Results: The protein S100B concentrations were maximal at 6 hours after the injury, which was followed by an abrupt fall, and subsequently slower release in the following two days with continual and significantly increased values (p<0.0001) in patients with poor outcome. Secondary increase in protein S100B at 72 hours was recorded in patients with lethal outcome (GOS 1). Dynamics of NSE changes was characterized by a secondary increase in concentrations at 72 hours after the injury in patients with poor outcome. Conclusion: Both markers have good predictive ability for poor neurological outcome, although NSE provides better discriminative potential at 72 hours after the brain injury, while protein S100B has better discriminative potential for mortality prediction.


2012 ◽  
Vol 91 (2) ◽  
pp. 230-239 ◽  
Author(s):  
Shuguang Yang ◽  
Yanhong Ma ◽  
Yong Liu ◽  
Haiping Que ◽  
Changqiang Zhu ◽  
...  

2022 ◽  
Vol Volume 18 ◽  
pp. 47-55
Author(s):  
Xin-Jiang Yan ◽  
Yang-Bo Li ◽  
Wei Liu ◽  
Hua-Yong Wu ◽  
Guo-Feng Yu

Author(s):  
Ridha Dharmajaya ◽  
Dina Keumala Sari ◽  
Ratna Akbari Ganie

Beratnya suatu cedera kepala akibat trauma akan membuat gangguan saraf pusat. Kerusakan saraf ini dapat dinilai dengan petandabiokimia yang tepat. Pemakaian petanda biokimia terhadap kerusakan otak mendapatkan perhatian yang banyak terutama ProteinS100B. Protein S100B adalah suatu ikatan kalsium dan protein yang meningkat cepat sesaat setelah cedera kepala. Kesulitannya adalahuntuk memastikan, berapa lama Protein S100B ini harus diukur. Jika berhubungan dengan kerusakan otak, ia tidak selalu terjadi pada24 jam pertama. Dapat terjadi pada 48–72 jam pasca cedera kepala, bahkan 120 jam pada kecederaan tersebut. Penelitian ini bertujuanuntuk mendapatkan kenasaban antara Protein S100B dengan GOS sebagai faktor peramalan yang akurat, mudah, tidak menyakitkan,untuk cedera kepala berat. Pengambilan serum darah untuk pemeriksaan kadar Protein S100B dilakukan pada 24, 48, 72 dan 120 jampasca trauma. Selanjutnya pengukuran dilakukan dengan menggunakan Enzyme Linked Immunosorbent Assay (ELISA). Keluaran pasienpasca perawatan dinilai menggunakan penggolongan Glasgow Outcome Scale (GOS), tiga bulan pasca kecederaan. Hasil pengukurankadar Protein S100B pada 120 jam pasca cedera kepala berat menunjukkan hubungan berlawanan yang kuat terhadap keluaran pasien.Pasien cedera kepala berat dengan kadar Protein S100B 120 jam pasca trauma yang tinggi, memiliki hasil keluaran yang buru


e-CliniC ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Ferry Sudarsono ◽  
Eko Prasetyo ◽  
Maximillian Ch. Oley ◽  
Fima L. F. G. Langi

 Abstract: Elevated serum laminin levels in patients with traumatic brain injury (TBI) have been documented, but studies on its ability to predict outcomes based on the CT Marshall and Glasgow Coma Scale (GCS) classification are still unclear. This study was aimed to evaluate the relationship between serum laminin levels and Marshall CT as well as GCS classification in COT patients. This was an observational and analytical study with a cross-sectional design. A scan was used to determine the CT Marshall and GCS classification in order to obtain the level of consciousness. Venous blood samples for laminin were drawn less than 24 hours post-trauma. Age and gender were recorded, and the variable selection was carried out gradually. Proportional regression models were used to assess changes in the CT Marshall and GCS classification associated with laminin levels. The result showed that the 32 patients with COT had a mean laminin level of 818.4 pg/mL. Patients were distributed almost uniformly in the six categories of the CT Marshall classification. Furthermore, the final regression model consisted of patients with the CT Marshall IV-VI classification having a serum laminin level of 316.74 pg/mL (95% CI 206.88; 426.60 pg/mL; p<0.001) higher than that of I-III. Meanwhile, after controlling for a number of other variables, the difference increased to 401.06 pg/mL (95% CI 264.84; 563.28 pg/ mL; p<0.001). The individual consciousness levels were measured by using GCS which consist of an inverse relationship with serum laminin levels. Each increase in the mean of GCS rate decreased the laminin value to about 49.10 pg/mL (95% CI 23.33; 74.96 pg/mL; p<0.001). In conclusion, laminin has a significant correlation with the CT Marshall and GCS classifications in patients with COT.Keywords: laminin, traumatic brain injury (TBI)  Abstrak: Peningkatan kadar serum laminin pada pasien dengan cedera otak akibat trauma (COT) telah didokumentasikan, namun studi tentang kemampuannya untuk memrediksi hasil berdasarkan klasifikasi CT Marshall dan GCS (Glasgow Coma Scale) masih terbatas. Penelitian ini bertujuan untuk mengevaluasi hubungan antara kadar laminin serum dengan klasifikasi CT Marshall dan GCS pada pasien COT. Jenis penelitian ialah analitik observasional dengan desain potong lintang. Pemeriksaan CT-scan digunakan untuk menentukan klasifikasi CT Marshall dan GCS digunakan untuk menentukan tingkat kesadaran. Sampel darah vena untuk laminin diambil kurang dari 24 jam pasca trauma. Usia dan jenis kelamin juga dicatat. Seleksi variabel dilakukan secara bertahap. Digunakan model regresi proporsional untuk menilai perubahan klasifikasi CT Marshall dan GCS terkait dengan kadar laminin. Hasil penelitian mendapatkan 32 pasien dengan COT yang masuk ke Instalasi Rawat Darurat Bedah (IRDB). Kadar rerata laminin ialah 818,4 pg/mL. Pasien didistribusikan hampir seragam dalam enam kategori dari klasifikasi CT Marshall. Model regresi akhir terdiri dari penderita dengan klasifikasi CT Marshall IV-VI rata-rata memiliki kadar laminin serum 316,74 pg/mL (95% CI 206,88; 426,60 pg/mL; p<0,001) lebih tinggi daripada mereka dengan kategori I-III. Setelah sejumlah variabel lain dikontrol, selisih tersebut bahkan naik menjadi 401,06 pg/mL (95% CI 264,84; 563,28 pg/mL; p<0,001). Tingkat kesadaran individu, diukur menggunakan GCS, sebaliknya memiliki hubungan terbalik dengan kadar laminin serum. Setiap kenaikan angka GCS rata-rata menurunkan nilai laminin hingga sekitar 49,10 pg/mL (95% CI 23,33; 74,96 pg/mL; p<0,001). Simpulan penelitian ini ialah laminin mempunyai korelasi bermakna dengan klasifikasi CT Marshall dan GCS pada pasien dengan COT.Kata kunci: laminin, cedera otak akibat trauma (COT)


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