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Impact of aging and comorbidities on ischemic stroke outcomes in preclinical animal models: A translational perspective

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Neuroinflammation, Stem Cells, and Stroke

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Cholesterol metabolic reprogramming mediates microglia-induced chronic neuroinflammation and hinders neurorestoration following stroke

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Leveraging single-cell RNA sequencing to unravel the impact of aging on stroke recovery mechanisms in mice

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Repair-associated macrophages increase after early-phase microglia attenuation to promote ischemic stroke recovery

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Microglial Responses to Brain Injury and Disease: Functional Diversity and New Opportunities

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A New Gene Set Identifies Senescent Cells and Predicts Senescence-Associated Pathways Across Tissues

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A Unique Type of Highly-Activated Microglia Evoking Brain Inflammation via Mif/Cd74 Signaling Axis in Aged Mice

Jin, C., Shao, Y., Zhang, X., Xiang, J., Zhang, R., Sun, Z., Mei, S., Zhou, J., Zhang, J., & Shi, L. (2021) · Aging and Disease · doi:10.14336/ad.2021.0520 · Cited by 53 · see citing works

Sevoflurane preconditioning protects experimental ischemic stroke by enhancing anti‐inflammatory microglia/macrophages phenotype polarization through GSK‐3β/Nrf2 pathway

Cai, M., Sun, S., Wang, J., Dong, B., Yang, Q., Li, T. X., Dong, H., Wang, S., & Hou, W. (2021) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13715 · Cited by 51 · see citing works

Intranasal delivery of interleukin-4 attenuates chronic cognitive deficits via beneficial microglial responses in experimental traumatic brain injury

Pu, H., Ma, C., Zhao, Y., Wang, Y., Zhang, W., Miao, W., Yu, F., Hu, X., Shi, Y., Leak, R. K., et al. (2021) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x211028680 · Cited by 47 · see citing works

STAT1 Contributes to Microglial/Macrophage Inflammation and Neurological Dysfunction in a Mouse Model of Traumatic Brain Injury

Zhao, Y., Ma, C., Chen, C., Li, S., Wang, Y., Yang, T., Stetler, R. A., Bennett, M. V. L., Dixon, C. E., Chen, J., et al. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.0682-22.2022 · Cited by 44 · see citing works

Oxidative stress as a bridge between age and stroke: A narrative review

Feng, S., Yang, M., Liu, S., He, Y. G., Deng, S., & Gong, Y. (2023) · Journal of Intensive Medicine · doi:10.1016/j.jointm.2023.02.002 · Cited by 47 · see citing works

Alzheimer’s genes in microglia: a risk worth investigating

Sudwarts, A., & Thinakaran, G. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00679-4 · Cited by 46 · see citing works

Microglia dynamic response and phenotype heterogeneity in neural regeneration following hypoxic-ischemic brain injury

Quan, H., & Zhang, R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1320271 · Cited by 44 · see citing works

Early onset senescence and cognitive impairment in a murine model of repeated mTBI

Schwab, N., Ju, Y., & Hazrati, L.-N. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01190-x · Cited by 39 · see citing works

Microglial heterogeneity in the ischemic stroke mouse brain of both sexes

del Águila, Á., Zhang, R., Yu, X., Dang, L., Xu, F., Zhang, J., Jain, V., Tian, J., Zhong, X., Sheng, H., et al. (2024) · Genome Medicine · doi:10.1186/s13073-024-01368-7 · Cited by 38 · see citing works

Imperatorin inhibits mitogen‐activated protein kinase and nuclear factor kappa‐B signaling pathways and alleviates neuroinflammation in ischemic stroke

Ge, J., Deng, S., Xue, Z., Liu, P., Yu, L., Li, J., Xia, S., Gu, Y., Bao, X., Lan, Z., et al. (2021) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13748 · Cited by 32 · see citing works

Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain

Lü, J., Li, H., Zhang, G., Yang, F., Zhang, X., Ping, A., Xu, Z., Gu, Y., Wang, R., Ying, D., et al. (2023) · Research · doi:10.34133/research.0287 · Cited by 30 · see citing works

Age-Related Alterations in Immune Function and Inflammation: Focus on Ischemic Stroke

Chen, Q.-X., Wu, M.-M., Tang, Q., Yan, P., & Zhu, L.-W. (2023) · Aging and Disease · doi:10.14336/ad.2023.0721-1 · Cited by 34 · see citing works

Inhibition of TGFβ-activated kinase 1 promotes inflammation-resolving microglial/macrophage responses and recovery after stroke in ovariectomized female mice

Liu, Y., Li, S., Wang, R., Pu, H., Zhao, Y., Ye, Q., & Shi, Y. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105257 · Cited by 26 · see citing works

A high fat, sugar, and salt Western diet induces motor‐muscular and sensory dysfunctions and neurodegeneration in mice during aging: Ameliorative action of metformin

Hong, S., Nagayach, A., Lü, Y., Peng, H., Duong, Q.-V., Pham, N. B., Vuong, C. A., & Bazan, N. G. (2021) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13726 · Cited by 24 · see citing works

The promise of exosome applications in treating central nervous system diseases

Mattingly, J., Li, Y., Bihl, J. C., & Wang, J. (2021) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13743 · Cited by 23 · see citing works

The age-dependent immune response to ischemic stroke

Tuohy, M. C., Hillman, E. M. C., Marshall, R. S., & Agalliu, D. (2022) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2022.102670 · Cited by 23 · see citing works

Targeted ablation of signal transducer and activator of transduction 1 alleviates inflammation by microglia/macrophages and promotes long-term recovery after ischemic stroke

Han, W., Pu, H., Li, S., Liu, Y., Zhao, Y., Xu, M., Chen, C., Wu, Y., Yang, T., Ye, Q., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02860-4 · Cited by 23 · see citing works

NG2 ‐glia crosstalk with microglia in health and disease

Zhang, Z., Li, X., Zhou, H., & Zhou, J. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13948 · Cited by 20 · see citing works

Bystanders or not? Microglia and lymphocytes in aging and stroke

Chauhan, A., & Nguyen, J. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.360345 · Cited by 21 · see citing works

Established and emerging techniques for the study of microglia: visualization, depletion, and fate mapping

Bobotis, B. C., Halvorson, T., Carrier, M., & Tremblay, M. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1317125 · Cited by 21 · see citing works

Metabolomic and transcriptional profiling reveals bioenergetic stress and activation of cell death and inflammatory pathways in vivo after neuronal deletion of NAMPT

Lundt, S., Zhang, N., Li, J.-L., Zhang, Z., Zhang, L., Wang, X., Bao, R., Cai, F., Sun, W., Ge, W., et al. (2021) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x21992625 · Cited by 19 · see citing works

Proposed practical protocol for flow cytometry analysis of microglia from the healthy adult mouse brain: Systematic review and isolation methods’ evaluation

Srakočić, S., Josić, P., Trifunović, S., Gajović, S., Grčević, D., & Glasnović, A. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.1017976 · Cited by 18 · see citing works

Activation of Swell1 in microglia suppresses neuroinflammation and reduces brain damage in ischemic stroke

Chen, B., Xie, C., Shi, T., Yue, S., Li, W., Huang, G., Zhang, Y., & Liu, W. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105936 · Cited by 18 · see citing works

The Need for New Biomarkers to Assist with Stroke Prevention and Prediction of Post-Stroke Therapy Based on Plasma-Derived Extracellular Vesicles

Popescu-Drigă, M. V., Cătălin, B., Olaru, D. G., Słowik, A., Plesnila, N., Hermann, D. M., & Popa‐Wagner, A. (2021) · Biomedicines · doi:10.3390/biomedicines9091226 · Cited by 18 · see citing works

Stroke-Induced Neurological Dysfunction in Aged Mice Is Attenuated by Preconditioning with Young Sca-1+ Stem Cells

Wlodarek, L., Alibhai, F. J., Wu, J., Li, S., & Li, R. (2022) · Stem Cells · doi:10.1093/stmcls/sxac019 · Cited by 17 · see citing works

Transcriptomics, single-cell sequencing and spatial sequencing-based studies of cerebral ischemia

Liu, J., Qing, T., He, M., Liu, X., Wu, Z., Huang, M., Liu, Z., Zhang, Y., Li, Z., Yang, W., et al. (2025) · European journal of medical research · doi:10.1186/s40001-025-02596-2 · Cited by 14 · see citing works

The Role of Aging in Intracerebral Hemorrhage

Huang, B., Chen, A., Sun, Y., & He, Q. (2024) · Brain Sciences · doi:10.3390/brainsci14060613 · Cited by 15 · see citing works

CLEC7A Knockdown Alleviates Ischemic Stroke by Inhibiting Pyroptosis and Microglia Activation

Li, W., Feng, X., Zhang, M., Wang, K., Huang, K., Zhao, Z., & Xia, M. (2024) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2312219 · Cited by 13 · see citing works

FBXO10 prevents chronic unpredictable stress‐induced behavioral despair and cognitive impairment through promoting RAGE degradation

Li, J., Zeng, Q.-C., Su, W., Song, M., Xie, M., & Mao, L. (2021) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13727 · Cited by 12 · see citing works

Microglia, the brain’s double agent

Yenari, M. A. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20968993 · Cited by 11 · see citing works

Brain and blood single-cell transcriptomics in acute and subacute phases after experimental strokePreprint

García‐Bonilla, L., Shahanoor, Z., Sciortino, R. K., Nazarzoda, O., Racchumi, G., Iadecola, C., & Anrather, J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.31.535150 · Cited by 12 · see citing works

Brain-targeted mild hypothermia ameliorates ischemic brain injury and promotes stroke recovery in aged mice

Lyu, J., Liu, L., Guo, M., Li, S., Su, W., Liu, J., & Ji, X. (2025) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x251346307 · Cited by 10 · see citing works

Transcriptional and neuroprotective effects of hexokinase-2 inhibitors administered after stroke

Won, S. J., Uruk, G., Mai, N., Tu, C., Ogut, D., Asatryan, S., Mocanu, E., Shon, R., Kim, K. S., Awakoaiye, K., et al. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03594-1 · Cited by 9 · see citing works

Stem cell-mediated recovery in stroke: partnering with the immune system

McMillan, N., McMillan, A., Kiliaan, P. C. J., Yahya, T., Thakkar, R., Weiner, H. L., Smirnakis, S. M., Yavagal, D. R., & Izzy, S. (2025) · Nature reviews. Neuroscience · doi:10.1038/s41583-025-00985-4 · Cited by 9 · see citing works

Integrative analysis of single-cell and bulk RNA sequencing unveils the senescence landscape in ischemic stroke

Fu, L., Yu, B., Zhang, Y., Cao, S., lv, B., Tian, Y., Chen, H., Yang, S., Hu, Y., Hua, J., et al. (2023) · Aging · doi:10.18632/aging.204804 · Cited by 11 · see citing works

Microglial deactivation by adeno‐associated virus expressing small‐hairpin GCH1 has protective effects against neuropathic pain development in a spinothalamic tract‐lesion model

Jung, H. H., Koh, C. S., Park, M., Kim, J. H., Woo, H., Lee, H., & Chang, J. W. (2021) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13751 · Cited by 6 · see citing works

A New Gene Set Identifies Senescent Cells and Predicts Senescence-Associated Pathways Across Tissues

(2021) · doi:10.21203/rs.3.rs-1034608/v1 · Cited by 6 · see citing works

Microglial AT1R Conditional Knockout Ameliorates Hypoperfusive Cognitive Impairment by Reducing Microglial Inflammatory Responses

Li, D., Zhang, Q., Yang, X., Zhang, G., Wang, J., Zhang, R., & Liu, Y. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.02.002 · Cited by 5 · see citing works

The Aging Immune System: A Critical Attack on Ischemic Stroke

Xu, W., Guo, Y., Zhao, L., Fu, R., Qin, X., Zhang, Y., Cheng, X., & Xu, S. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04464-2 · Cited by 5 · see citing works

Regulatory T cells promote microglia-mediated synapse engulfment and functional recovery via the OPN-CD74 axis after spinal cord injury in mice

Liu, R., Yan, H., Liu, X., Xie, Y., Li, Y., Wang, Z., Huang, H., Yu, Z., Qu, W., Wang, M., et al. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03661-7 · Cited by 5 · see citing works

Emerging Techniques for the Study of Microglia: Visualization, Depletion and Fate MappingPreprint

Bobotis, B. C., Halvorson, T., Carrier, M., & Tremblay, M. (2023) · Preprints.org · doi:10.20944/preprints202308.2190.v1 · Cited by 3 · see citing works

The meal Maketh the Microglia: Why studying microglial phagocytosis is critical to stroke research

Morrison, V. E., & Bix, G. J. (2023) · Neurochemistry International · doi:10.1016/j.neuint.2023.105488 · Cited by 3 · see citing works

Comprehensive analysis of multiple species identifies novel molecular signatures and pathways involved in aging

Cai, W., Chong, K., Zhou, B., Zhao, Y., Lao, B., & Yin, L. (2025) · Genomics · doi:10.1016/j.ygeno.2025.111161 · Cited by 2 · see citing works

Heterogeneity of Microglia in Ischemic Stroke from the Perspective of Single-Cell RNA Sequencing: Subset Characteristics, Mechanisms and Therapeutic Potential

Tian, D., Yang, J., Wang, Z., Lan, J., Shi, T., Xu, S., Zhao, M., He, P., Wang, J., & Xing, L. (2026) · Journal of Central Nervous System Disease · doi:10.1177/11795735261452744 · Cited by 2 · see citing works

Endothelial-specific ACKR1 overexpression attenuates macrophage infiltration and blood–brain barrier disruption after ischemic stroke

Guo, M., Fang, H., Tang, S., Shao, Q., Liu, J., & Ji, X. (2026) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x261461872 · Cited by 2 · see citing works

Microglial Responses to MSC-EVs Treatment in Animal and Cellular Models of Ischemic Stroke: a Systematic Review with Meta-analysis

Bernardi, L. P., Schlickmann, T. H., Carello‐Collar, G., Bastiani, M. A. D., Zimmer, E. R., Braganhol, E., Rohden, F., & Souza, D. O. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05025-x · Cited by 2 · see citing works

Transcriptomic Analysis of lncRNAs and their mRNA Networks in Cerebral Ischemia in Young and Aged Mice

Zeng, Y., Xue, T., Zhang, D., & Lv, M. (2023) · Combinatorial Chemistry & High Throughput Screening · doi:10.2174/1386207326666230619091603 · Cited by 2 · see citing works

IFN-β as a therapeutic agent for influenza A virus infection in old mice

Wu, W., Alexander, J. S., Song, Y., Booth, J. L., Ford, A. K., Metcalf, J. P., & Drevets, D. A. (2026) · GeroScience · doi:10.1007/s11357-026-02198-8 · Cited by 1 · see citing works

From Gene Discovery to Stroke Risk: C5orf24's Pivotal Role Uncovered

Gao, R., Xu, Y., Zhang, M., Zeng, Q., Zhu, G., Su, W., & Wang, R. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04802-y · Cited by 1 · see citing works

Potential Involvement of Keratan Sulfate in the Heterogeneity of Microglia

Ohgomori, T., & Jinno, S. (2021) · Trends in Glycoscience and Glycotechnology · doi:10.4052/tigg.2038.1e

Potential Involvement of Keratan Sulfate in the Heterogeneity of Microglia

Ohgomori, T., & Jinno, S. (2021) · Trends in Glycoscience and Glycotechnology · doi:10.4052/tigg.2038.1j

Impact of the NAD+ salvage pathway on the motor system and bioenergetics

Lundt, S. (2023) · doi:10.32469/10355/96990

Additional file 2 of Targeted ablation of signal transducer and activator of transduction 1 alleviates inflammation by microglia/macrophages and promotes long-term recovery after ischemic stroke

Han, W., Pu, H., Li, S., Liu, Y., Zhao, Y., Xu, M., Chen, C., Wu, Y., Yang, T., Ye, Q., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26607454

Additional file 1 of Targeted ablation of signal transducer and activator of transduction 1 alleviates inflammation by microglia/macrophages and promotes long-term recovery after ischemic stroke

Han, W., Pu, H., Li, S., Liu, Y., Zhao, Y., Xu, M., Chen, C., Wu, Y., Yang, T., Ye, Q., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26607451

Aging Inhibits Emergency Angiogenesis and Exacerbates Neuronal Damage by Downregulating DARS2

Liu, D., Weng, M., Wang, R., Fu, W., Zhang, L., Wang, C., Liu, M., Shen, T., Ren, J., Song, Y., et al. (2026) · Journal of Inflammation Research · doi:10.2147/jir.s527147

Endothelial energy failure as a therapeutic target in elderly strokes

Nasoohi, S., Ebrahimi, F., Brown, C. M., & Huber, J. D. (2026) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x261437917

Microglial state transitions dominate the brain immune response in the subacute phase after cardiac arrest

Dang, L., Zhang, R., Zhang, J., He, P., Yu, X., Rehman, A. U., del Águila, Á., Jain, V., Tian, J., Xu, E., et al. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03874-4

Dysfunctional Mitochondria in Microglia Drive Cognitive Aging and Neurodegeneration via cGAS–STING

Ma, G., Wang, E., Yan, X., Xu, X. X., Li, X. Y., Ma, X., Yang, W.-H., Zeng, J., & Xie, X. (2026) · Neuroscience Bulletin · doi:10.1007/s12264-026-01657-8 · Cited by 1 · see citing works

TREM2 deficiency causes region-specific brain effects in a mouse model of cerebral amyloid angiopathy

Mercado, C., Amaro, A., Martínez-Pinto, J., Vidal, R., Jury, N., & Lasagna‐Reeves, C. A. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-04065-x

Early infiltration of ischemia-conditioned Tregs attenuates BBB damage via suppressing neutrophil extracellular traps in ischemic stroke

Li, H., Zhang, X., Lü, J., Lu, L., Chen, J., Ping, A., Lu, Y., Jin, Z., Tang, S., Wang, R., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118102

Transcriptomic and functional studies reveal undermined chemotactic and angiostimulatory properties of aged microglia during stroke recovery

Jiang, L., Mu, H., Xu, F., Xie, D., Su, W., Xu, J., Sun, Z., Liu, S., Luo, J., Shi, Y., et al. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20902542 · Cited by 45 · see citing works

Abstract 109: Depletion of Microglia Does Not Improve Functional Outcomes in Aged Mice After Transient Focal Ischemia

Lee, S. M., Hudobenko, J., Lee, J., McCullough, L. D., & Chauhan, A. (2020) · Stroke · doi:10.1161/str.51.suppl_1.109

Decoding the Transcriptional Response to Ischemic Stroke in Young and Aged Mouse Brain

Androvic, P., Kirdajova, D., Tureckova, J., Zucha, D., Rohlova, E., Abaffy, P., Kriska, J., Valny, M., Anderova, M., Kubista, M., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107777 · Cited by 118 · see citing works

Transcriptomic characterization of microglia activation in a rat model of ischemic stroke

Deng, W., Mandeville, E. T., Terasaki, Y., Li, W., Holder, J. C., Chuang, A. T., Ning, M., Arai, K., Lo, E. H., & Xing, C. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20932870 · Cited by 69 · see citing works

Abstract P727: Single-Cell RNA Sequencing Identifies Ifi27l2a as a Novel Gene Involved in Regulating Microglial Inflammation in the Context of Aging and Stroke

Kim, G. S., Stephenson, J. M., Wu, T., Gutierrez, M. E. C., Wythe, J. D., & Marrelli, S. P. (2021) · Stroke · doi:10.1161/str.52.suppl_1.p727