Isotope Dilution Analysis of Myelin Basic Protein Degradation After Brain Injury

Author(s):  
Andrew K. Ottens
2012 ◽  
Vol 116 (1) ◽  
pp. 246-253 ◽  
Author(s):  
Robert E. Ayer ◽  
Nazanin Jafarian ◽  
Wanqiu Chen ◽  
Richard L. Applegate ◽  
Austin R. T. Colohan ◽  
...  

Object Intracranial surgery causes cortical injury from incisions, hemorrhage, retraction, and electrocautery. The term “surgical brain injury” (SBI) has been developed to categorize this injury inherent to the procedure. Neuroinflammation plays a significant role in SBI. Traditional antiinflammatory therapies are often limited by their immunosuppressive side effects and poor CNS penetration. This study uses mucosal tolerance to develop an immune system that is tolerant to brain myelin basic protein (MBP) so that inflammation can be suppressed in a timely and site-specific manner following surgical disruption of the blood-brain barrier. Methods A standard SBI model using CD57 mice was used. Nasopharyngeal mucosa was exposed to vehicle, ovalbumin, or MBP to develop mucosal tolerance to these antigens. Immunological tolerance to MBP was confirmed in vivo through hypersensitivity testing. Neurological scores, cerebral edema, and interleukin (IL)–1β and transforming growth factor (TGF)–β1 cytokine levels were measured 48 hours postoperatively. Results Hypersensitivity testing confirmed the development of immune tolerance to MBP. Myelin basic protein–tolerant mice demonstrated reduced neurological injury, less cerebral edema, decreased levels of IL-1β, and increased levels of TGFβ1 following SBI. Conclusions Developing preoperative immunological tolerance to brain antigens through mucosal tolerance provides neuroprotection, reduces brain edema, and modulates neuroinflammation following SBI.


Author(s):  
Juan Sebastian Cruz-Méndez ◽  
María Paula Herrera-Sánchez ◽  
Ángel Enrique Céspedes-Rubio ◽  
Iang Schroniltgen Rondón-Barragán

Abstract Background Myelin basic protein (MBP) is one of the most important structural components of the myelin sheaths in both central and peripheral nervous systems. MBP has several functions including organization of the myelin membranes, reorganization of the cytoskeleton during the myelination process, and interaction with the SH3 domain in signaling pathways. Likewise, MBP has been proposed as a marker of demyelination in traumatic brain injury and chemical exposure. Methods The aim of this study was to molecularly characterize the myelin basic protein a (mbpa) gene from the Colombian native fish, red-bellied pacu, Piaractus brachypomus. Bioinformatic tools were used to identify the phylogenetic relationships, physicochemical characteristics, exons, intrinsically disordered regions, and conserved domains of the protein. Gene expression was assessed by qPCR in three models corresponding to sublethal chlorpyrifos exposure, acute brain injury, and anesthesia experiments. Results mbpa complete open reading frame was identified with 414 nucleotides distributed in 7 exons that encode 137 amino acids. MBPa was recognized as belonging to the myelin basic protein family, closely related with orthologous proteins, and two intrinsically disordered regions were established within the sequence. Gene expression of mbpa was upregulated in the optic chiasm of the chlorpyrifos exposed fish in contrast to the control group. Conclusions The physicochemical computed features agree with the biological functions of MBP, and basal gene expression was according to the anatomical distribution in the tissues analyzed. This study is the first molecular characterization of mbpa from the native species Piaractus brachypomus.


Author(s):  
Simone Bohnert ◽  
Christoph Wirth ◽  
Werner Schmitz ◽  
Stefanie Trella ◽  
Camelia-Maria Monoranu ◽  
...  

AbstractThe aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury.


2021 ◽  
pp. 1-6
Author(s):  
Camilla Omann ◽  
Kendall M. Lawrence ◽  
Mallory L. Hunt ◽  
James K. Moon ◽  
Jamuna Buchanan ◽  
...  

Abstract Objectives: The objective of this study was to investigate changes in serum biomarkers of acute brain injury, including white matter and astrocyte injury during chronic foetal hypoxaemia. We have previously shown histopathological changes in myelination and neuronal density in fetuses with chronic foetal hypoxaemia at a level consistent with CHD. Methods: Mid-gestation foetal sheep (110 ± 3 days gestation) were cannulated and attached to a pumpless, low-resistance oxygenator circuit, and incubated in a sterile fluid environment mimicking the intrauterine environment. Fetuses were maintained with an oxygen delivery of 20–25 ml/kg/min (normoxemia) or 14–16 ml/kg/min (hypoxaemia). Myelin Basic Protein and Glial Fibrillary Acidic Protein serum levels in the two groups were assessed by ELISA at baseline and at 7, 14, and 21 days of support. Results: Based on overlapping 95% confidence intervals, there were no statistically significant differences in either Myelin Basic Protein or Glial Fibrillary Acidic Protein serum levels between the normoxemic and hypoxemic groups, at any time point. No statistically significant correlations were observed between oxygen delivery and levels of Myelin Basic Protein and Glial Fibrillary Acidic Protein. Conclusion: Chronic foetal hypoxaemia during mid-gestation is not associated with elevated serum levels of acute white matter (Myelin Basic Protein) or astrocyte injury (Glial Fibrillary Acidic Protein), in this model. In conjunction with our previously reported findings, our data support the hypothesis that the brain dysmaturity with impaired myelination found in fetuses with chronic hypoxaemia is caused by disruption of normal developmental pathways rather than by direct cellular injury.


2006 ◽  
Vol 98 (3) ◽  
pp. 700-712 ◽  
Author(s):  
Ming Cheng Liu ◽  
Veronica Akle ◽  
Wenrong Zheng ◽  
Jason Kitlen ◽  
Barbara O'Steen ◽  
...  

2017 ◽  
Vol 51 (2) ◽  
pp. 157-165
Author(s):  
Le Zhang ◽  
Zhong-Yuan Ren ◽  
Jin-Long Ma ◽  
Xiao-Ping Xia

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