Topic Overview and Questions
Acute brain injury often triggers lesions, which, in their turn, may affect the immune system of a patient to a considerable degree (Venereau, Ceriotti, & Bianchi, 2015). As a result, the latter is likely to develop immunosuppression, which will lead to the change in the brain-immune signaling (Frank, Weber, Watkins, & Maier, 2015). Thus, encouraging damage-associated molecular pattern (DAMP) signals in a patient should be viewed as the means of addressing the identified aftermath of a brain injury, especially when meeting the needs of patients that have suffered a stroke (Edye, Lopez-Castejon, Allan, & Brough, 2013).
In their article, Liesz et al. (2015) shed light on the use of HMGB1 signaling as a part of DAMP signals as a way of addressing the problems associated with immune modulation (Korbelik, 2016). Furthermore, the authors of the study consider the effects of soluble mediators that are emitted from the patient’s brain as the possible solution for the problems associated with the interaction between the immune system and the brain that occurs after a stroke (Liesz et al., 2015).
The research, therefore, raises the question of whether the study of brain-released alarmins, in general, and high mobility group proteins, such as HMGB1, in particular, may help determine whether there is a connection between systemic brain injuries and the changes in the peripheral immune system activity (Tintor et al., 2013). The results of the research indicate that a significant rise in the HMGB1 serum concentrations can be observed after a severe brain injury (Liesz et al., 2015). The study outcomes also point to the fact that neither neutralization of antibodies, nor the RAGE receptor removal as the means of preventing the release of HMGB1 and the further drop in the immune levels, as well as the sensory-motor deficit in patients has any tangible effect (Versluys, Tarkowski, & Van den Ende, 2017). Further experiments, however, showed that HMGB1-RAGE signaling could be used as a tool for identifying and preventing the incidences of immune-mediated complications in stroke victims (Liesz et al., 2015).
Critical Review of the Findings
The fact that a noticeable rise in the HMGB1 serum concentration levels occurs only in the instances of large infarcts shows that the use of the identified tool may not be viewed as sensible when addressing the issues associated with minor strokes. In other words, the study results show that the use of the serum may fail to have the expected positive outcomes in the incidences that involve mild strokes (McDonald et al., 2014). Therefore, there is a threat that the suggested approach may be less efficient than expected (Yang et al., 2015).
Nevertheless, it is remarkable that the results of the study also pointed to a significant drop in the infarct volume levels, as well as a reduction in the neurological deficit rates, and among mice. Furthermore, the fact that the number of lethal outcomes has been reduced greatly needs to be listed among the essential outcomes of the experiment needs to be mentioned: “Intriguingly, despite the lack of effect on infarct size and neurological deficit, 7 d mortality was substantially reduced in RAGE/mice (p 0.008, n 22) and tended also to be lower in anti-HMGB1-treated mice (p 0.07, n 17)” (Liesz et al., 2015, p. 588).
The analysis of the biological maturity of HMGB1 should also be brought up among the advantages of the study. A deeper insight into the modifications of HMGB1 is rather welcome given the lack of information about the subject matter (Asai & Asai, 2013), as well as the absence of consistency in managing the identified problem (Kroemer & Galluzzi, 2016). The opportunities in nursing and healthcare that the analysis provided by Liesz et al. (2015) are truly ample. Thus, the quality of care can be increased significantly.
A detailed characterization of the early phase after brain injury should also be considered one of the primary strengths of the paper. Apart from making a compelling argument about the use of HMGB1 in reducing the threat of a lethal outcome (Gero et al., 2013), Liesz et al. (2015) also convey an important message about the means of detecting the problem at the earliest stages of its development and, therefore, managing it in a manner as efficient and expeditious as possible (Hackam, Afrazi, Good, & Sodhi, 2013). Given the mortality rates in the identified area, one must admit that the significance of the identified element of the findings is very high (Moller, 2014).
Finally, the discovery of the connection between RAGE and myeloid-derived suppressor cells (MDSC) serves as the basis for the further design of a comprehensive treatment strategy and a nursing approach. By measuring the levels of RAGE in the patient, one will be able to identify the threats to their health and, thus, design an appropriate treatment strategy (Li, Chaichana, Rodarte, Quiñones-Hinojosa, & Guerrero-Cazares, 2014). Therefore, the findings of the study can be deemed as outstandingly useful for a better understanding of the subject matter (Liesz et al., 2015).
Paper Significance: A Brief Summary
The incidences of a brain injury are quite common; therefore, the effects that they have on the patient’s immune system need to be studied extensively so that the framework for addressing the problem successfully could be designed. Which is even more important, the very nature of the issues developed by the patient after the injury needs to be studied closer. Thus, the connection between the HMGB1 release after the brain damage and the signaling process mediated with the help of the RAGE receptors and be explored in a more detailed manner.
Herein lies the significance of the research under analysis. Liesz et al. (2015) shed light on the issue of addressing immune system issues triggered by acute brain trauma, i.e., the area that has not been explored thoroughly yet and, therefore, needs further analysis. As a result, prerequisites for an all-embracing follow-up study can be created. Which is even more important, the findings of the article by Liesz et al. (2015) can be viewed as the foundation for building a new and improved approach toward managing the needs of people that have suffered a stroke or experienced another kind of brain injury.
In other words, the results of the study create the basis for a significant improvement in the quality of care. By focusing on the identification of the links between the HMGB1 release and the signaling process, one will be able to detect the emerging issues at the earliest stages of their development and, therefore, prevent the problem from growing out of proportion. Furthermore, the use of the study findings is likely to prevent the development of comorbidities in patients. Setting the premises for a rapid improvement of the quality of care, the study findings should be viewed as quite significant.
Asai C & Asai, A (2013) Involvement of toll-like receptors in ischemic stroke induced neuronal damage. Journal of Neurological Disorders & Stroke 2(2): 1051-1053.
Edye, ME, Lopez-Castejon, G, Allan, SM, Brough, D (2013) Acidosis drives damage-associated molecular pattern (DAMP)-induced interleukin-1 secretion via a caspase-1-independent pathway. Journal of Biological Chemistry 288(42): 30485-30494. Web.
Frank, MG, Weber, MD, Watkins, RL, Maier, SF (2015) Stress sounds the alarmin: the role of the danger-associated molecular pattern HMGB1 in stress-induced neuroinflammatory priming. Brain, Behavior, and Immunity 48(1): 1-7. Web.
Gero, D, Szoleczky, P, Modis, K, Pribis, JP, Al-Abed, Y, Yang, H,… Szabo, C (2013) Identification of Pharmacological Modulators of HMGB1-Induced Inflammatory Response by Cell-Based Screening. PLoS One 8(6): 1-18. Web.
Hackam, DJ., Afrazi, A, Good, M, Sodhi, CP (2013) Innate immune signaling in the pathogenesis of necrotizing enterocolitis. Clinical and Developmental Immunology 2013(475415): 1-11. Web.
Korbelik, M (2016) Sphingolipid activity in oxidative stress response and tumor immunity. Austin Journal of Vaccines & Immunotherapeutics 3(1): 1008-1009.
Kroemer, G, Galluzzi, L (2016) Autophagy-dependent danger signaling and adaptive immunity to poorly immunogenic tumors. Oncotarge 1(1): 1-7.
Li, Q, Chaichana, KL, Rodarte, JJ, Quiñones-Hinojosa, A, Guerrero-Cazares, H (2014) Mesenchymal stem cells as alternative therapy for brain disorders and their interaction with the immune system. In Neuro-Immune Interactions in the Adult Central Nervous System (pp. 87-108). Hauppauge, NY: Nova Science Publishers, Inc.
Liesz, A, Dalpke, A, Mracsko, E, Antoine, DJ, Roth, S, Zhou, W,… Veltkamp, R (2015) DAMP signaling is a key pathway inducing immune modulation after brain injury. Journal of Neuroscience 35(2): 583–598. Web.
McDonald, KA, Huang, H, Tohme, S, Loughran, P, Ferrero, K, Billiar, T, & Tsung, A (2014) Toll-like receptor 4 (TLR4) antagonist eritoran tetrasodium attenuates liver ischemia and reperfusion injury through inhibition of high-mobility group box protein B1 (HMGB1) signaling. Molecular Medicine 20(1): 639–648. Web.
Moller, AR (2014) The role of neuroplasticity and the immune system in recovery from strokes and other forms of brain trauma. Journal of Neurology & Stroke 1(3): 16.
Tintor, N, Ross, A, Kanehara, K, Yamada, K, Fan, L, Kemmerling, B,…Saijoa, Y (2013) Layered pattern receptor signaling via ethylene and endogenous elicitor peptides during Arabidopsis immunity to bacterial infection. PNAS Early Edition 110: 1-6. Web.
Venereau, E, Ceriotti, C, & Bianchi, ME (2015) DAMPs from cell death to new life. Frontiers in Immunology 1(1): 1-11. doi:10.3389/fimmu.2015.00422
Versluys, M, Tarkowski, LP, & Van den Ende, W (2017) Fructans as DAMPs or MAMPs: Evolutionary prospects, cross-tolerance, and multistress resistance potential. Perspective 7(1): 1-7. Web.
Yang, H, Wang, H, Ju, Z, Raga, ZZ, Lundbäck, P, Long, W,… Al-Abed, Y (2015) MD-2 is required for disulfide HMGB1–dependent TLR4 signaling. Journal of Experimental Medicine 212(1): 5-14. Web.