Cited by 238Neuroinflammation and Neurodegeneration MechanismsAcute Ischemic Stroke ManagementTraumatic Brain Injury and Neurovascular Disturbances

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Inflammation in Ischemic Brain Injury: Timing Is Important

Kriz, Jasna·2006·Critical Reviews™ in Neurobiology

DOI 10.1615/critrevneurobiol.v18.i1-2.150

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Abstract

Inflammation is a defense reaction against diverse insults that serves to remove noxious agents and to limit their detrimental effects. There is increasing evidence that post-ischemic inflammation plays an important role in brain ischemia. However, whether inflammatory processes are deleterious or beneficial to recovery is presently a matter of debate and controversy. Experimentally and clinically, stroke is followed by an acute and a prolonged inflammatory response characterized by the production of inflammatory cytokines, leukocyte and monocyte infiltration in the brain, and the activation of resident glial cells. These events may contribute to ischemic brain injury. Several groups report conflicting results regarding the role of inflammation and effects of anti-inflammatory treatments in cerebral ischemia. Experimental studies employing knockout mice for different cytokines and chemokines provide only partial answers. This highlights the importance of clarifying the role of the immune response in pathological changes at the site of ischemic lesions in the brain. Here, we describe dual effects of the brain's inflammatory response and new evidence for a neuroprotective role of proliferating microglial cells in ischemia. In addition, we discuss a potential role of post-ischemic inflammation in brain regeneration and modulation of synaptic plasticity.

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Background
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Self-citation
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Background
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Background
Retracted
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Background
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Background
[Retracted] Therapeutical Significance of Serpina3n Subsequent Cerebral Ischemia via Cytotoxic Granzyme B Inactivation
Aslam, M. S., Aslam, M. S., Aslam, K. S., et al. (2022) · BioMed Research International · doi:10.1155/2022/1557010 · Cited by 10
“This multifaceted pathophysiology involves stimulation of numerous immune responses that leads to neuroinflammation with heterogenous forms of neuronal death [4].”
Background
Retracted
Neuronal Damage Using Fluoro-Jade B Histofluorescence and Gliosis in the Gerbil Septum Submitted to Various Durations of Cerebral Ischemia
Park, C. W., Lee, J., Ahn, J. H., Lee, D. H., Cho, G., Yan, B. C., Park, J. H., Kim, I. H., Lee, H. Y., Won, M., et al. (2013) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-013-9967-y · Cited by 10
“Like many other neurodegenerative disorders, reactive gliosis associated with cerebral ischemia involves both astrocytes and microglia (Kriz 2006).”
Background
Role of Microglia in Stroke
Cipriani, R., Domerq, M., Martín, A., & Matute, C. (2024) · Advances in neurobiology · doi:10.1007/978-3-031-55529-9_23 · Cited by 10
Analysis of Neutrophil/Lymphocyte ratio and Thiol/Disulfide homeostasis parameters in patients admitted to the emergency department with ischemic stroke
Yilmaz, A. B., Gökhan, Ş., Şener, A., et al. (2018) · Pakistan Journal of Medical Sciences · doi:10.12669/pjms.346.16242 · Cited by 9
The role of medical gas in stroke: an updated review
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Differential anti-ischemic efficacy and therapeutic time window of trans- and cis-hinokiresinols: Stereo-specific antioxidant and anti-inflammatory activities
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Neutrophil-Mediated Progression of Mild Cognitive Impairment to Dementia
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“…occurs a few hours after occlusion and reaches maximal levels at early time Neutrophils move rapidly from the bone marrow and conduct an innate immune response that occurs a few hours after occlusion and reaches maximal levels at early time points of one to three of one to three days [109,111].”
Background
L‐F001, a multifunctional fasudil–lipoic acid dimer, antagonizes hypoxic–ischemic brain damage by inhibiting the TLR4/MyD88 signaling pathway
Zhou, R., Wu, L., Jin, N., et al. (2023) · Brain and Behavior · doi:10.1002/brb3.3280 · Cited by 8
“Oxygen radicals cause cell death not only due to direct hypoxic–ischemic damage but also due to ischemia reperfusion (reoxygenation), which promotes the continuous occurrence of necrosis–apoptosis (Hassell et al., 2015; Kriz, 2006).”
Background
Inflammation, Oxidative Stress, and Cerebral Stroke: Basic Principles
Tiwari, S. K., Mishra, P., & Rajavashisth, T. B. (2019) · Springer eBooks · doi:10.1007/978-981-13-1453-7_2 · Cited by 9
Melissa officinalis: a memory enhancer remedy
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“Stroke is the fourth leading cause of death worldwide and the major cause of disability, ischemic injury is associated with inflammation and free radical metabolites (Kriz, 2006).”
Background
Nonselective Cation Channels and Links to Hippocampal Ischemia, Aging, and Dementia
MacDonald, J. F., Belrose, J. C., Xie, Y., & Jackson, M. F. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-4756-6_37 · Cited by 8
MRS3997, a dual adenosine A2A/A2B receptor agonist, reduces brain ischemic damage and alleviates neuroinflammation in rats
Dettori, I., Bulli, I., Venturini, M., Magni, G., Cherchi, F., Rossi, F., Lee, H., Pedata, F., Jacobson, K. A., Pugliese, A. M., et al. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110214 · Cited by 7
“As known from the literature, already from the first hours after an ischemic insult an overactivation of microglial cells occurs (Block et al., 2007; Kriz, 2006; Schwartz, 2003), that triggers morphological changes in astrocytes (R ¨ ohl et al., 2007).”
Differential effect of transient global ischaemia on the levels of γ‐aminobutyric acid type A (GABAA) receptor subunit mRNAs in young and older rats
Montori, S., Dos-Anjos, S., Poole, A. V., Regueiro-Purriños, M. M., Llorente, I. L., Darlison, M. G., Fernández‐López, A., & Martínez‐Villayandre, B. (2012) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2012.01254.x · Cited by 7
Spatial and Temporal MRI Profile of Ischemic Tissue after the Acute Stages of a Permanent Mouse Model of Stroke
Bogaert-Buchmann, A., Poittevin, M., Po, C., Dupont, D., Sebrié, C., 冨田, 裕., Tran‐Dinh, A., Seylaz, J., Pinard, E., Méric, P., et al. (2013) · The Open Neuroimaging Journal · doi:10.2174/1874440001307010004 · Cited by 7
microRNA‑196a attenuates ischemic brain injury in rats by directly targeting high mobility group A1
Hu, J., & Shen, W. (2019) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2019.7152 · Cited by 7
“In addition, ischemic brain injury has been suggested to be associated with widespread molecular and biochemical changes, inf lammatory responses, oxidative stress, free radical production and neuronal apoptosis (34-36).”
Background
Decreased a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 activity and neurologic outcome in patients with successful resuscitation of out-of-hospital cardiac arrest: A prospective observational study
Ohbe, H., Kudo, D., Yamanouchi, S., et al. (2016) · Journal of Critical Care · doi:10.1016/j.jcrc.2016.08.011 · Cited by 6
“Systemic inflammation may exacerbate local processes in the brain in ischemic brain injury [31].”
Background
Anti-Inflammatory Properties of Botanical Extracts Contribute to Their Protective Effects in Brain Edema in Cerebral Ischemia
Panickar, K. S. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-411462-3.00001-1 · Cited by 6
Galanin's implications for post-stroke improvement
Song, J., & Kim, O. Y. (2016) · Anatomy & Cell Biology · doi:10.5115/acb.2016.49.4.223 · Cited by 6
Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents
Choudhary, R. C., Shoaib, M., Hayashida, K., Yin, T., Miyara, S. J., d'Abramo, C., Heuser, W., Shinozaki, K., Kim, N., Takegawa, R., et al. (2023) · Cells · doi:10.3390/cells12111548 · Cited by 6
“Furthermore, inflammatory processes start immediately after ischemia and lead to cerebral injury [64,65] through several phases.”
Background
Effects of subcutaneous low molecular weight heparin and intravenous unfractionated heparin on serum S100 concentrations in patients with cerebrovascular diseases
Wang, S., Wang, L., Zhang, X., et al. (2011) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2011.794 · Cited by 5
“Infl ammatory processes have been indicated to play the key, mainly detrimental roles in the pathophysiological changes of ischemic stroke (1) .”
Background
Serum inflammatory markers after postcardiac arrest resuscitation: Surrogate markers of efficacy, therapeutic targets, or innocent bystanders*
Qureshi, A. I. (2008) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181843e62 · Cited by 4
Effects of lysophosphatidic acid receptor 5 on NLRC4 inflammasome in brain tissues of transient cerebral ischemia/reperfusion rat
Zhang, X., Huang, T., Lang, L., & Yu, L. (2022) · Human & Experimental Toxicology · doi:10.1177/09603271221078870 · Cited by 4
MacGreen mice: a novel tool to investigate inflammation following experimental stroke
Chen, S., Bennet, L., & McGregor, A. L. (2015) · Journal of Experimental Stroke and Translational Medicine · doi:10.4172/1939-067x.1000143 · Cited by 5
Morphological and immunohistochemical analysis of proteins CASPASE 3 and XIAP in rats subjected to cerebral ischemia and chronic alcoholism
Schiavoni, V. S., da Silva, J. P., Neto, F. S. L., de Assis, M. L. C., Tazima, M. D. F. G. S., de Carvalho, C. A. M., Tirapelli, D. P. D. C., Carlotti, C. G., Colli, B. O., & Tirapelli, L. F. (2018) · Acta Cirúrgica Brasileira · doi:10.1590/s0102-865020180080000001 · Cited by 4
N-3 polyunsaturated fatty acids induce granulopoiesis and early monocyte polarization in the bone marrow of a tMCAO rat model
Horváth, E., Huţanu, A., Orădan, A. V., Chiriac, L., Muntean, D.-L., Nagy, E. E., & Dobreanu, M. (2019) · Revista română de medicină de laborator · doi:10.2478/rrlm-2019-0004 · Cited by 3
“Some authors found that the very first infiltrating elements are neutrophils (from 30 minutes to 12 hours), (6, 7, 8) whereas others observed the early recruitment of blood-derived macrophages (at 12 hours) and a later appearance of neutrophils (1-3 days) (9), which is why the target of this research was the bone marr…”
BackgroundInfluential
Cord Blood as a Treatment for Stroke
Willing, A. E., & Foran, E. A. (2014) · Springer eBooks · doi:10.1007/978-3-319-11481-1_5 · Cited by 3
“In a review of the field, Kriz (Kriz 2006) suggested that after a stroke there is an early proliferative, neuroprotective response followed by a later pro-inflammatory response.”
Background
Anti-inflammatory Effects of Different Fractions Isolated from Modified Boyanghwano-tang Extract in LPS-stimulated Microglial Cells
Son, H. Y., & Park, Y. (2009) · The Korea Journal of Herbology · Cited by 3
Metabolic Alterations in Acute Cerebral Ischemia.
Poenaru, A. M., Ionescu, M., Albu, C. V., Rogoveanu, I., & Bălşeanu, T. A. (2022) · PubMed Central · doi:10.12865/chsj.48.03.02 · Cited by 2
“02 257 High serum cholesterol is also associated with a higher risk of ischemic stroke in the large cerebral arteries [18,23].”
Background
Injury to repair: Functions of microglia and monocyte-derived cells in ischemic stroke
Martynowicz, R., Sullivan, D. P., & Batra, A. (2025) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2025.108422 · Cited by 4
A novel long-galanin peptide from non-mammalian vertebrates mitigates the inflammatory response in IBD models via the biased GALR2/β-arrestin2 pathway
Lai, S., Kong, X., Xue, J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-66335-1 · Cited by 2
“Additionally,galaninisimportantinpost-strokein ﬂ ammation,contributing to the in ﬁ ltration of leukocytes and monocytes in the brain 57 .”
Protective Role of Galanin during Chemically Induced Inflammation in Zebrafish Larvae
Nowik, N., Przyborowska, A., Sienkiewicz, W., et al. (2021) · Biology · doi:10.3390/biology10020099 · Cited by 2
“Galanin plays an important part in poststroke inflammation, including the secretion of inflammatory cytokines and leukocyte/monocyte infiltration in the brain [13].”
Stem Cells: How We Could Restore the Brain Function After Ischemic Damage
Kokaia, Z., & Darasalia, V. (2015) · Springer eBooks · doi:10.1007/978-4-431-54490-6_7 · Cited by 2
Perilesional Gliosis Is Associated with Outcome after Perinatal Stroke
Yu, S. S., Lam, C., Shinde, S., et al. (2021) · Journal of Pediatric Neurology · doi:10.1055/s-0041-1728687 · Cited by 2
MAPK and pro-inflammatory mediators in the walls of brain blood vessels following cerebral ischemia
Maddahi, A. (2012) · Lund University Publications (Lund University) · Cited by 2
Derangement in Homeostasis of Neutrophil Elastase and its Inhibitory Systems in Ischemic Stroke Patients
Kunder, M., Kutty, A. V. M., & Lakshmaiah, V. (2023) · Biomedical & Pharmacology Journal · doi:10.13005/bpj/2669 · Cited by 1
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Yan, H. Q., Osier, N. D., Korpon, J. R., Bales, J. W., Kline, A. E., Wagner, A. K., & Dixon, C. E. (2015) · Cited by 1
MICROGLIA ACTIVATION IN A RODENT MODEL OF AN ALCOHOL USE DISORDER: THE IMPORTANCE OF PHENOTYPE, INITIATION, AND DURATION OF ACTIVATION
Marshall, S. A. (2013) · UKnowledge (University of Kentucky) · Cited by 1
Vascular Inflammation in Ischemic Stroke: Adhesion Receptors Controlling Leukocyte–Endothelial Interactions
Rodrigues, S. F., & Granger, D. N. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8915-3_3 · Cited by 1
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Authors: Kriz, J.
Venue: Critical Reviews™ in Neurobiology
Publisher: Begell House
Published: 2006
Volume: 18
Issue: 1-2
Pages: 145-157
ISSN: 0892-0915 (ISSN-L)
DOI: 10.1615/critrevneurobiol.v18.i1-2.150
OpenAlex: W1982308497
Cited by: 238
References: 0
Citations by year: 2026: 3 · 2025: 3 · 2024: 13 · 2023: 12 · 2022: 11 · 2021: 8 · 2020: 7 · 2019: 21 · 2018: 10 · 2017: 8 · 2016: 13 · 2015: 13 · 2014: 21 · 2013: 23 · 2012: 18
FWCI: 3.92
Type: journal article
Language: en
Open access: closed
Locations: Critical Reviews in Neurobiology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords: post-ischemic inflammation, cerebral ischemia, stroke, neuroinflammation, inflammatory cytokines, leukocyte infiltration, monocyte infiltration, glial activation, microglia, neuroprotection, anti-inflammatory therapy, cytokine knockout mice, brain regeneration, synaptic plasticity
MeSH terms: Animals, Brain Ischemia, Chemotaxis, Leukocyte, Encephalitis, Gliosis, Humans, Cytokines, Microglia, Cytoprotection, Brain Infarction, Cell Proliferation

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Inflammation in Ischemic Brain Injury: Timing Is Important

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