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Understanding The Impact Of Ischemic Stroke On Peripheral Immune Responses


Ischemic stroke is also known as cerebral ischemia or brain ischemia. Ischemic stroke is most common types of stroke which accounts for more than 87% of the stroke case in the UK. In this type of stroke, a blockage occurs in the artery that supplies blood and oxygen to brain. As a result, there is lack of oxygen and blood supply to the brain cells and tissues which contribute to the death of and damage to the brain cells. Clinical studied have shown that there is potential relationship between the stroke and the immune response. Evidence suggests that the factors involved in the peripheral immune system are associated with inflammation at the post-stroke condition.


This research proposal aims to make a comprehensive discussion on how the ischemic stroke impacts the procedures and factors involve in the peripheral immune system. Here the study will present a literature review in which it will compare and review the data of different relevant research papers in relation to discuss the selected research topic. The expected outcome of this research proposal is to present an evidence-based research study on the impacts of ischemic stroke on the peripheral immune system, that will assist health practitioners and nurses to develop the clear understanding about this topic.


Following an ischemic stroke in human body there occurs several chances in different body organs, especially in spleen and brain. These changes are strongly associated with instigating the organs involve in the peripheral immune system to develop the necessary immune response against the structural and functional changes thereby bringing the interna environment of body hack to the normal state.


This research study aims to discuss how Ischemic stroke impacts on the functional process of the peripheral immune system. This study also aims to discuss the important roles of spleen and brain in developing peripheral immunes response following a stroke.


Ischemic stroke has potential impacts on the peripheral immune’s response

Null hypothesis:

Ischemic stroke does not impact on the peripheral immune’s response

Background to investigation (literature review):

Ischemic stroke leads to stroke-initiated infection (SAI) which accounts for more than 20% of the death at the post stroke condition (Rayasam et al. 2018). Spleen is the highly vascularized lymphoid organ that is severely affected after the ischemic stroke which cause structural and functional changes in spleen. Spleen consists of while pulp and red pulp. The red pulp plays crucial roles in maintaining proper immune response against any bacteria or microbes enter into body. Red pulp contains several immunes response cells such as B cell, NK cells, microphases monocytes and lymphoid cell which are strongly associated with generating the specific immune response thereby preparing body to develop the specific antibody against antigen (bacteria or microbe) thereby protecting body from any kind of infection Jayaraj et al. 2019). Spleen acts as the reservoir of various immunes cells which are associated in developing the necessary proinflammatory responses during and after the ischemic stoke. At the post stroke condition there is high chances of causing SAI inside the body (Meng et al. 2019). Due to the development of stroke-initiated infection (SAI) the red pulp of spleen becomes activated which then activates the T cell and B cell region. Then from the T cell zone there is secretion of the T cells and dendritic cells that act as the potential innate immune cell. On the other hand, B cells are secreted from the B cell zone. After activation, B cells, T cells and dendritic cells leave spleen and develop the immune response by secreting cytokines that protect the body from any kind of infection and injuries insides the body. After an ischemic stroke there is high risk of infection in different organs inside the body thereby the enhancing the risk towards mortality and morbidity. Splenic marginal zone (MZ) B cells are the innate like lymphocytes that develop strong defense system early against any stroke related bacterial infection (Yang et al. 2017). In case of post stroke infection, the body is unable to develop the defense system due to the lack of production of Splenic marginal zone (MZ) B cells, which causes deficiency inn capturing the blood borne antigens and the suppression of the circulating IgM. This condition is associated with the repeated bacterial infection in lung, which leads to reduced ability of lung alveoli to be involved in the gaseous exchanges. Immediate after stroke, splenic B-cells causes the subsequent changes in the peripheral immunes system by activating the immunes elements such as lymphocytes, CD++ factors and macrophages (Wang et al. 2018). These elements then activate the Follicular Dendritic Cell (FDC) network which located in the B cells. These network plays crucial roles in producing high amount of CD 21 factors and associated antigens which then work against the infection thereby protecting the body from any kind of bacterial infection. As stated by Li et al. (2018), Splenic marginal zone (MZ) B cells plays significant roles in maintaining apparent differentiation as well as separating brain from the peripheral circulation. The Splenic marginal zone (MZ) B cells is involved in maintaining proper balance among all the solutes, cells and files at the blood brain interface thereby maintaining the hemostatic environment inside the spleen. Ischemic stroke develops the immunes response in the peripheral circulation by eliciting the activation of that different subset of immunological factors such as macrophages, cytokines and immunoglobulin receptors. In the post-stroke condition, there is subsequence damages and repair in the Splenic marginal zone (MZ) B cells which is strongly associated with the changes in the peripheral immune system (Yang et al. 2017). After ischemic stroke peripheral immunes cells undergo the necessary intracellular mechanism during which they interact with the Splenic marginal zone (MZ) B cells thereby making the dynamic chances in the integrity and structure of Splenic marginal zone (MZ) B cells.

Rayasam et al. (2018) mentioned in this study that although the clear reason behind the interception of brain and peripheral immunes system after the stroke is still obscure the clinical evidence suggests that, in the post stroke there is sever damage in the BBB which send signal to the immune cells in the peripheral immunes system thereby activating the peripheral immune repose into the circulation. On of the drawback of this research paper is it fails to discuss the proper reason behind this activation of the peripheral immune cells immediate after the damage of BBB following a stroke. In this context Rayasam et al. (2018) mentioned that the activation of the peripheral immunes cells by the brain signal following stroke associated with initiating the effectives changes inside the body after the stroke to maintain proper homeostasis condition inside the brain that can assist the brain cells back to their normal functions.

Rayasam et al. (2018) also mentioned in this research paper that, the interaction of peripheral immune cell with the BBB causes the dynamic changes in the structure and function of BBB. After causing these changes in the BBB, the immune cells can subsequently entry into the brain and then detect the chemoattractant gradient thereby imitating the neuroimmune interaction. In this context Wang et al. (2018) mentioned that the peripheral immune cells while entering through the damaged BBB on their way to brain there can occurs two types of incidence such as whether it can lead to exacerbate the danged condition of BBB of it can provides the proper protection to the BBB for initiating its repair and remodelling process. On the contrary Shi et al. (2018) argued in this context by stating that there is no proper clinical evidence regarding the two types of interception with the BBB and the peripheral immunes cells while penetrating through the changed as well as damaged BBB.

Following the damage of BB there occurs the detachment of different endothelium cells that triggers the leucocytes entry into the brain (Jayaraj et al. 2019, Meng et al. 2019). Then the further infiltration of peripheral immunes factors such as leucocytes, macrophages and neutrophil which lead to the activation of intracellular adhesion molecule‐1(ICAM‐1) t thereby promoting vasoconstriction (Venkat et al. 2018.). As a result, different proinflammatory substances are produces such as histamine, TNF- α and protease that leads to the neurotoxicity and degradation of BBB.

Experimental design (research method):

Search method:

Research method is the process that outlines the systematic pathways that a researcher follows for accomplishing any research study. Search strategy is one of the important aspects on the research methods which present the tools or methods that a researcher has used to search for the relevant databased (Oztemel and Gursev, 2020). In primary research, researcher generally used the qualitative and qualitative methods to collect statistical data. On the other hand, in case of the secondary research, researcher use online database, key terms ad Boolean logic for searching het appropriate researcher papers.

In this research study, the researcher has used the clinical online database for collecting the relevant research paper. Here researcher has used CINHAL, MEDLINE. British National Index, PubMed, psych info and Cochrane Library (Central Register of Controlled Trials). Although search by using the PubMed has been removes afterward as it is seen that majority of the research papers that are searcher by using this online database are repeated. As stated by Snyder (2019), a good research needs a comprehensive and well-organized search which will assist the researcher to search such research papers that can provide relevant as well as authentic and valid information about the research topic. Here by using these online databases, researcher is able to select the authentic, trustworthy and high value research papers which will assist the researcher to answer the research question n and meet the research aim and objectives. For collecting the authentic and highly relevant research papers, by using the online database, the researcher of this study has used the following key terms that assisted the researcher to narrow the literature search.

Key terms:

research database research database research database

Boolean operator:

In this study the researcher has used the Boolean operator for narrowing the literature search thereby collecting only the relevant and specific research peppers. As mentioned by Oztemel and Gursev (2020), use of Boolean logic is highly effective search tool that enables the research to narrow the search result thereby selective authentic, highly valid and trustworthy research papers. Here researcher has used AND OR logic gate by using the key terms which assisted the researcher to select evidence based and high value research papers. The Boolean logic that is used in this study is as follows:

Brain* OR Central Nervous System* AND Stroke* OR Ischemic stroke *AND Blood Brain Barrier (BBB)* AND Peripheral immunes system* And Cytokines* AND lymphocytes* OR immunes system*.

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Millstones of investigation:

Researcher will follow a preset timescale to accomplish this entire research study. The timescale set for completing this research study is 3 weeks. During this time, researchers will make further research on selected research papers in terms of collecting the authentic database from them, which will assist the researcher to conduct systematic data analysis of collected evidences. As mentioned by Chernyadyev et al. (2018), before starting nay investigation researcher must set the milestone which will guide the researcher to plan, execute and accomplish the entire research study systematically. During the planning stages of this research study the researcher will set the objectives and aim of this study. In the execution stage researcher execute the proposed research methods, research strategies and the expected outcomes of the research process. In the accomplishment stage, researcher will use the relevant research design, research approach, data collection and analysis tool thereby meeting research objectives. For accomplishing this study researcher will follow the below mentioned time scale that will assist the researcher to accomplish the research study systemically.

research database

Reference list:

Alishahi, M., Farzaneh, M., Ghaedrahmati, F., Nejabatdoust, A., Sarkaki, A. and Khoshnam, S.E., 2019. NLRP3 inflammasome in ischemic stroke: as possible therapeutic target. International Journal of Stroke, 14(6), pp.574-591.

Huang, X., Hussain, B. and Chang, J., 2021. Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms. CNS neuroscience & therapeutics, 27(1), pp.36-47.

Jayaraj, R.L., Azimullah, S., Beiram, R., Jalal, F.Y. and Rosenberg, G.A., 2019. Neuroinflammation: friend and foe for ischemic stroke. Journal of neuroinflammation, 16(1), pp.1-24.

Khoshnam, S.E., Winlow, W., Farzaneh, M., Farbood, Y. and Moghaddam, H.F., 2017. Pathogenic mechanisms following ischemic stroke. Neurological Sciences, 38(7), pp.1167-1186.

Lasek-Bal, A., Jedrzejowska-Szypulka, H., Student, S., Warsz-Wianecka, A., Zareba, K., Puz, P., Bal, W., Pawletko, K. and Lewin-Kowalik, J., 2019. The importance of selected markers of inflammation and blood-brain barrier damage for short-term ischemic stroke prognosis. J Physiol Pharmacol, 70(2), pp.209-217.

Li, Y., Zhu, Z.Y., Huang, T.T., Zhou, Y.X., Wang, X., Yang, L.Q., Chen, Z.A., Yu, W.F. and Li, P.Y., 2018. The peripheral immune response after stroke—a double edge sword for blood‐brain barrier integrity. CNS neuroscience & therapeutics, 24(12), pp.1115-1128.

Meng, H., Zhao, H., Cao, X., Hao, J., Zhang, H., Liu, Y., Zhu, M.S., Fan, L., Weng, L., Qian, L. and Wang, X., 2019. Double-negative T cells remarkably promote neuroinflammation after ischemic stroke. Proceedings of the National Academy of Sciences, 116(12), pp.5558-5563.

Rayasam, A., Hsu, M., Kijak, J.A., Kissel, L., Hernandez, G., Sandor, M. and Fabry, Z., 2018. Immune responses in stroke: how the immune system contributes to damage and healing after stroke and how this knowledge could be translated to better cures?. Immunology, 154(3), pp.363-376.

Shi, K., Wood, K., Shi, F.D., Wang, X. and Liu, Q., 2018. Stroke-induced immunosuppression and poststroke infection. Stroke and vascular neurology, 3(1), pp.34-41.

Venkat, P., Chen, J. and Chopp, M., 2018. Exosome-mediated amplification of endogenous brain repair mechanisms and brain and systemic organ interaction in modulating neurological outcome after stroke. Journal of Cerebral Blood Flow & Metabolism, 38(12), pp.2165-2178.

Wang, X., Xuan, W., Zhu, Z.Y., Li, Y., Zhu, H., Zhu, L., Fu, D.Y., Yang, L.Q., Li, P.Y. and Yu, W.F., 2018. The evolving role of neuro‐immune interaction in brain repair after cerebral ischemic stroke. CNS neuroscience & therapeutics, 24(12), pp.1100-1114.

Yang, B., Hamilton, J.A., Valenzuela, K.S., Bogaerts, A., Xi, X., Aronowski, J., Mays, R.W. and Savitz, S.I., 2017. Multipotent adult progenitor cells enhance recovery after stroke by modulating the immune response from the spleen. Stem cells, 35(5), pp.1290-1302.

Yang, L., Han, B., Zhang, Z., Wang, S., Bai, Y., Zhang, Y., Tang, Y., Du, L., Xu, L., Wu, F. and Zuo, L., 2020. Extracellular Vesicle–Mediated Delivery of Circular RNA SCMH1 Promotes Functional Recovery in Rodent and Nonhuman Primate Ischemic Stroke Models. Circulation, 142(6), pp.556-574.

Zakeri, A., Jadhav, A.P., Sullenger, B.A. and Nimjee, S.M., 2021. Ischemic stroke in COVID-19-positive patients: an overview of SARS-CoV-2 and thrombotic mechanisms for the neurointerventionalist. Journal of neurointerventional surgery, 13(3), pp.202-206.

Oztemel, E. and Gursev, S., 2020. Literature review of Industry 4.0 and related technologies. Journal of Intelligent Manufacturing, 31(1), pp.127-182.

Snyder, H., 2019. Literature review as a research methodology: An overview and guidelines. Journal of Business Research, 104, pp.333-339.

Chernyadyev, S.A., Ufimtseva, M.A., Vishnevskaya, I.F., Bochkarev, Y.M., Ushakov, A.A., Beresneva, T.A., Galimzyanov, F.V. and Khodakov, V.V., 2018. Fournier’s gangrene: literature review and clinical cases. Urologia internationalis, 101, pp.91-97.

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