Abstract
Cerebral stroke has assorted causes, disrupting the cerebral blood flow and subsequently damaging the brain tissues in affected areas. Stroke is the third primary cause of death and disability in adults around the globe. In approximately 25–40% of cerebral stroke patients, the neurological signs are initiated during the early hours. The mechanism involved in the pathophysiology of cerebral stroke are oxidative stress and inflammation. Oxidative stress takes place when there is an impairment to the balance of antioxidant generation with reactive oxygen species (ROS) and other free radicals/oxidants. The brain is extremely vulnerable to oxidative stress owing to the high consumption of body oxygen to produce energy and free radicals, which may cause damage to the main cellular components, such as lipids, proteins, and DNA, and contributing to late-stage apoptosis and inflammation. Inflammation plays significant role in the pathogenesis of cerebral stroke and associated brain damage. Experimentally and clinically, ischemic brain injury takes place because of the initiation of severe and extended inflammatory progression. These processes include activation of brain microglial cells, production of pro-inflammatory mediators (cytokines and chemokines), and infiltration of numerous inflammatory cells such as neutrophils, T-cells, monocyte/macrophages, and natural killer cells into the ischemic brain regions, which initiates neuronal injuries and cell death mechanisms. In this chapter, we focus on the cellular and molecular evidence for oxidative stress and inflammation in cerebral stroke. In addition, we highlight certain current findings and knowledge of the neuroprotective strategies that target oxidative stress/inflammation and their implications in the pathogenesis of cerebral stroke.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- BBB:
-
Blood–brain barrier
- NO:
-
Nitric oxide
- RNS:
-
Reactive nitrogen species
- ROS:
-
Reactive oxygen species
- SOD:
-
Superoxide dismutase
- TNF:
-
Tumor necrosis factor
References
Donnan, G. A., Fisher, M., Macleod, M., & Davis, S. M. (2008). Stroke. Lancet, 371(9624), 1612–1623.
Lo, E. H., Dalkara, T., & Moskowitz, M. A. (2003). Mechanisms, challenges and opportunities in stroke. Nature Reviews. Neuroscience, 4(5), 399–415.
Kriz, J., & Lalancette-Hebert, M. (2009). Inflammation, plasticity and real-time imaging after cerebral ischemia. Acta Neuropathologica, 117(5), 497–509.
Lakhan, S. E., Kirchgessner, A., & Hofer, M. (2009). Inflammatory mechanisms in ischemic stroke: Therapeutic approaches. Journal of Translational Medicine, 7, 97.
Dirnagl, U., Iadecola, C., & Moskowitz, M. A. (1999). Pathobiology of ischaemic stroke: An integrated view. Trends in Neurosciences, 22(9), 391–397.
Kim, Y., Davidson, J. O., Green, C. R., Nicholson, L. F., O’’Carroll, S. J., & Zhang, J. (2017). Connexins and pannexins in cerebral ischemia. Biochimica et Biophysica Acta, 1860(1), 224–236.
Muir, K. W., Tyrrell, P., Sattar, N., & Warburton, E. (2007). Inflammation and ischaemic stroke. Current Opinion in Neurology, 20(3), 334–342.
Yilmaz, G., & Granger, D. N. (2008). Cell adhesion molecules and ischemic stroke. Neurological Research, 30(8), 783–793.
Emsley, H. C., & Hopkins, S. J. (2008). Acute ischaemic stroke and infection: Recent and emerging concepts. Lancet Neurology, 7(4), 341–353.
McColl, B. W., Allan, S. M., & Rothwell, N. J. (2009). Systemic infection, inflammation and acute ischemic stroke. Neuroscience, 158(3), 1049–1061.
Baird, T. A., Parsons, M. W., Barber, P. A., Butcher, K. S., Desmond, P. M., Tress, B. M., Colman, P. G., Jerums, G., Chambers, B. R., & Davis, S. M. (2002). The influence of diabetes mellitus and hyperglycaemia on stroke incidence and outcome. Journal of Clinical Neuroscience, 9(6), 618–626.
Elkind, M. S., Cheng, J., Rundek, T., Boden-Albala, B., & Sacco, R. L. (2004). Leukocyte count predicts outcome after ischemic stroke: The Northern Manhattan Stroke Study. Journal of Stroke and Cerebrovascular Diseases, 13(5), 220–227.
McColl, B. W., Rothwell, N. J., & Allan, S. M. (2007). Systemic inflammatory stimulus potentiates the acute phase and CXC chemokine responses to experimental stroke and exacerbates brain damage via interleukin-1- and neutrophil-dependent mechanisms. The Journal of Neuroscience, 27(16), 4403–4412.
Amantea, D., Nappi, G., Bernardi, G., Bagetta, G., & Corasaniti, M. T. (2009). Post-ischemic brain damage: Pathophysiology and role of inflammatory mediators. The FEBS Journal, 276(1), 13–26.
Kriz, J. (2006). Inflammation in ischemic brain injury: Timing is important. Critical Reviews in Neurobiology, 18(1–2), 145–157.
Schilling, M., Besselmann, M., Leonhard, C., Mueller, M., Ringelstein, E. B., & Kiefer, R. (2003). Microglial activation precedes and predominates over macrophage infiltration in transient focal cerebral ischemia: A study in green fluorescent protein transgenic bone marrow chimeric mice. Experimental Neurology, 183(1), 25–33.
Tanaka, R., Komine-Kobayashi, M., Mochizuki, H., Yamada, M., Furuya, T., Migita, M., Shimada, T., Mizuno, Y., & Urabe, T. (2003). Migration of enhanced green fluorescent protein expressing bone marrow-derived microglia/macrophage into the mouse brain following permanent focal ischemia. Neuroscience, 117(3), 531–539.
Buck, B. H., Liebeskind, D. S., Saver, J. L., Bang, O. Y., Yun, S. W., Starkman, S., Ali, L. K., Kim, D., Villablanca, J. P., Salamon, N., Razinia, T., & Ovbiagele, B. (2008). Early neutrophilia is associated with volume of ischemic tissue in acute stroke. Stroke, 39(2), 355–360.
Gerhard, A., Neumaier, B., Elitok, E., Glatting, G., Ries, V., Tomczak, R., Ludolph, A. C., & Reske, S. N. (2000). In vivo imaging of activated microglia using [11C]PK11195 and positron emission tomography in patients after ischemic stroke. Neuroreport, 11(13), 2957–2960.
Lindsberg, P. J., Carpen, O., Paetau, A., Karjalainen-Lindsberg, M. L., & Kaste, M. (1996). Endothelial ICAM-1 expression associated with inflammatory cell response in human ischemic stroke. Circulation, 94(5), 939–945.
Price, C. J., Menon, D. K., Peters, A. M., Ballinger, J. R., Barber, R. W., Balan, K. K., Lynch, A., Xuereb, J. H., Fryer, T., Guadagno, J. V., & Warburton, E. A. (2004). Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: An imaging-based study. Stroke, 35(7), 1659–1664.
Vidale, S., Consoli, A., Arnaboldi, M., & Consoli, D. (2017). Postischemic inflammation in acute stroke. Journal of Clinical Neurology, 13(1), 1–9.
Zhu, Y., Yang, G. Y., Ahlemeyer, B., Pang, L., Che, X. M., Culmsee, C., Klumpp, S., & Krieglstein, J. (2002). Transforming growth factor-beta 1 increases bad phosphorylation and protects neurons against damage. The Journal of Neuroscience, 22(10), 3898–3909.
Bonaventura, A., Liberale, L., Vecchie, A., Casula, M., Carbone, F., Dallegri, F., & Montecucco, F. (2016). Update on inflammatory biomarkers and treatments in ischemic stroke. International Journal of Molecular Sciences, 17(12).
Barone, F. C., & Feuerstein, G. Z. (1999). Inflammatory mediators and stroke: New opportunities for novel therapeutics. Journal of Cerebral Blood Flow and Metabolism, 19(8), 819–834.
Ferrarese, C., Mascarucci, P., Zoia, C., Cavarretta, R., Frigo, M., Begni, B., Sarinella, F., Frattola, L., & De Simoni, M. G. (1999). Increased cytokine release from peripheral blood cells after acute stroke. Journal of Cerebral Blood Flow and Metabolism, 19(9), 1004–1009.
Lucas, S. M., Rothwell, N. J., & Gibson, R. M. (2006). The role of inflammation in CNS injury and disease. British Journal of Pharmacology, 147(Suppl 1), S232–S240.
Spera, P. A., Ellison, J. A., Feuerstein, G. Z., & Barone, F. C. (1998). IL-10 reduces rat brain injury following focal stroke. Neuroscience Letters, 251(3), 189–192.
Swanson, R. A., Ying, W., & Kauppinen, T. M. (2004). Astrocyte influences on ischemic neuronal death. Current Molecular Medicine, 4(2), 193–205.
Kim, J. S., Gautam, S. C., Chopp, M., Zaloga, C., Jones, M. L., Ward, P. A., & Welch, K. M. (1995). Expression of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 after focal cerebral ischemia in the rat. Journal of Neuroimmunology, 56(2), 127–134.
Dimitrijevic, O. B., Stamatovic, S. M., Keep, R. F., & Andjelkovic, A. V. (2007). Absence of the chemokine receptor CCR2 protects against cerebral ischemia/reperfusion injury in mice. Stroke, 38(4), 1345–1353.
Hughes, P. M., Allegrini, P. R., Rudin, M., Perry, V. H., Mir, A. K., & Wiessner, C. (2002). Monocyte chemoattractant protein-1 deficiency is protective in a murine stroke model. Journal of Cerebral Blood Flow and Metabolism, 22(3), 308–317.
Soriano, S. G., Amaravadi, L. S., Wang, Y. F., Zhou, H., Yu, G. X., Tonra, J. R., Fairchild-Huntress, V., Fang, Q., Dunmore, J. H., Huszar, D., & Pan, Y. (2002). Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury. Journal of Neuroimmunology, 125(1–2), 59–65.
Coyle, J. T., & Puttfarcken, P. (1993). Oxidative stress, glutamate, and neurodegenerative disorders. Science, 262(5134), 689–695.
Cuzzocrea, S., Riley, D. P., Caputi, A. P., & Salvemini, D. (2001). Antioxidant therapy: A new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacological Reviews, 53(1), 135–159.
Allen, C. L., & Bayraktutan, U. (2009). Oxidative stress and its role in the pathogenesis of ischaemic stroke. International Journal of Stroke, 4(6), 461–470.
Davis, S. M., & Pennypacker, K. R. (2017). Targeting antioxidant enzyme expression as a therapeutic strategy for ischemic stroke. Neurochemistry International, 107, 23–32.
Yamagata, K., Ichinose, S., Miyashita, A., & Tagami, M. (2008). Protective effects of ebselen, a seleno-organic antioxidant on neurodegeneration induced by hypoxia and reperfusion in stroke-prone spontaneously hypertensive rat. Neuroscience, 153(2), 428–435.
Ozkan, O. V., Yuzbasioglu, M. F., Ciralik, H., Kurutas, E. B., Yonden, Z., Aydin, M., Bulbuloglu, E., Semerci, E., Goksu, M., Atli, Y., Bakan, V., & Duran, N. (2009). Resveratrol, a natural antioxidant, attenuates intestinal ischemia/reperfusion injury in rats. The Tohoku Journal of Experimental Medicine, 218(3), 251–258.
Duan, X., Wen, Z., Shen, H., Shen, M., & Chen, G. (2016). Intracerebral hemorrhage, oxidative stress, and antioxidant therapy. Oxidative Medicine and Cellular Longevity, 2016, 1203285.
Zhao, H., Han, Z., Ji, X., & Luo, Y. (2016). Epigenetic regulation of oxidative stress in ischemic stroke. Aging and Disease, 7(3), 295–306.
Zhao, S. C., Ma, L. S., Chu, Z. H., Xu, H., Wu, W. Q., & Liu, F. (2017). Regulation of microglial activation in stroke. Acta Pharmacologica Sinica, 38(4), 445–458.
Duris, K., Lipkova, J., & Jurajda, M. (2017). Cholinergic anti-inflammatory pathway and stroke. Current Drug Delivery, 14(4), 449–457.
Chen, C., Chu, S. F., Liu, D. D., Zhang, Z., Kong, L. L., Zhou, X., & Chen, N. H. (2018). Chemokines play complex roles in cerebral ischemia. Neurochemistry International, 112, 146–158.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Tiwari, S.K., Mishra, P., Rajavashisth, T. (2019). Inflammation, Oxidative Stress, and Cerebral Stroke: Basic Principles. In: Patnaik, R., Tripathi, A., Dwivedi, A. (eds) Advancement in the Pathophysiology of Cerebral Stroke. Springer, Singapore. https://doi.org/10.1007/978-981-13-1453-7_2
Download citation
DOI: https://doi.org/10.1007/978-981-13-1453-7_2
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-1452-0
Online ISBN: 978-981-13-1453-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)