Collaborators GBDS. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18:439–58.

Article  Google Scholar 

Phipps MS, Cronin CA. Management of acute ischemic stroke. BMJ. 2020;368:l6983.

Article  PubMed  Google Scholar 

Gu Z, Cui J, Brown S, Fridman R, Mobashery S, Strongin AY, et al. A highly specific inhibitor of matrix metalloproteinase-9 rescues laminin from proteolysis and neurons from apoptosis in transient focal cerebral ischemia. J Neurosci. 2005;25:6401–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cui J, Chen S, Zhang C, Meng F, Wu W, Hu R, et al. Inhibition of MMP-9 by a selective gelatinase inhibitor protects neurovasculature from embolic focal cerebral ischemia. Mol Neurodegener. 2012;7:21.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci. 2009;32:638–47.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Asahi M, Asahi K, Jung JC, del Zoppo GJ, Fini ME, Lo EH. Role for matrix metalloproteinase 9 after focal cerebral ischemia: effects of gene knockout and enzyme inhibition with BB-94. J Cereb Blood Flow Metab. 2000;20:1681–9.

Article  CAS  PubMed  Google Scholar 

Mi Y, Qi G, Vitali F, Shang Y, Raikes AC, Wang T, et al. Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration. Nat Metab. 2023;5:445–65.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen ZP, Wang S, Zhao X, Fang W, Wang Z, Ye H, et al. Lipid-accumulated reactive astrocytes promote disease progression in epilepsy. Nat Neurosci. 2023;26:542–54.

Article  CAS  PubMed  Google Scholar 

Ioannou MS, Jackson J, Sheu SH, Chang CL, Weigel AV, Liu H, et al. Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity. Cell. 2019;177:1522–35.e14.

Article  CAS  PubMed  Google Scholar 

Morant-Ferrando B, Jimenez-Blasco D, Alonso-Batan P, Agulla J, Lapresa R, Garcia-Rodriguez D, et al. Fatty acid oxidation organizes mitochondrial supercomplexes to sustain astrocytic ROS and cognition. Nat Metab. 2023;5:1290–302.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li X, Zhang J, Li D, He C, He K, Xue T, et al. Astrocytic ApoE reprograms neuronal cholesterol metabolism and histone-acetylation-mediated memory. Neuron. 2021;109:957–70.e8.

Article  CAS  PubMed  Google Scholar 

Lee H, Cho S, Kim MJ, Park YJ, Cho E, Jo YS, et al. ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes. Cell Rep. 2023;42:113183.

Article  CAS  PubMed  Google Scholar 

Tcw J, Qian L, Pipalia NH, Chao MJ, Liang SA, Shi Y, et al. Cholesterol and matrisome pathways dysregulated in astrocytes and microglia. Cell. 2022;185:2213–33.e25.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hernandez-Anzaldo S, Brglez V, Hemmeryckx B, Leung D, Filep JG, Vance JE, et al. Novel role for matrix metalloproteinase 9 in modulation of cholesterol metabolism. J Am Heart Assoc. 2016;5:e004228.

Macrae IM. Preclinical stroke research-advantages and disadvantages of the most common rodent models of focal ischaemia. Br J Pharmacol. 2011;164:1062–78.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ji Y, Gao Q, Ma Y, Wang F, Tan X, Song D, et al. An MMP-9 exclusive neutralizing antibody attenuates blood-brain barrier breakdown in mice with stroke and reduces stroke patient-derived MMP-9 activity. Pharm Res. 2023;190:106720.

Article  CAS  Google Scholar 

Lopez T, Mustafa Z, Chen C, Lee KB, Ramirez A, Benitez C, et al. Functional selection of protease inhibitory antibodies. Proc Natl Acad Sci USA. 2019;116:16314–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li Y, Chopp M, Chen J, Wang L, Gautam SC, Xu YX, et al. Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab. 2000;20:1311–9.

Article  CAS  PubMed  Google Scholar 

Takao K, Kobayashi K, Hagihara H, Ohira K, Shoji H, Hattori S, et al. Deficiency of schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and behavioral phenotypes related to schizophrenia. Neuropsychopharmacology. 2013;38:1409–25.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dubal DB, Kashon ML, Pettigrew LC, Ren JM, Finklestein SP, Rau SW, et al. Estradiol protects against ischemic injury. J Cereb Blood Flow Metab. 1998;18:1253–8.

Article  CAS  PubMed  Google Scholar 

Carswell HV, Dominiczak AF, Macrae IM. Estrogen status affects sensitivity to focal cerebral ischemia in stroke-prone spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2000;278:H290–4.

Article  CAS  PubMed  Google Scholar 

Ji YB, Wu YM, Ji Z, Song W, Xu SY, Wang Y, et al. Interrupted intracarotid artery cold saline infusion as an alternative method for neuroprotection after ischemic stroke. Neurosurgical Focus 2012; 33:E10.

Ji YB, Gao Q, Tan XX, Huang XW, Ma YZ, Fang C, et al. Lithium alleviates blood-brain barrier breakdown after cerebral ischemia and reperfusion by upregulating endothelial Wnt/beta-catenin signaling in mice. Neuropharmacology. 2021;186:108474.

Article  CAS  PubMed  Google Scholar 

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–8.

Article  CAS  PubMed  Google Scholar 

Bouscary A, Quessada C, Rene F, Spedding M, Turner BJ, Henriques A, et al. Sphingolipids metabolism alteration in the central nervous system: Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Semin Cell Dev Biol. 2021;112:82–91.

Article  CAS  PubMed  Google Scholar 

Limaye V, Li X, Hahn C, Xia P, Berndt MC, Vadas MA, et al. Sphingosine kinase-1 enhances endothelial cell survival through a PECAM-1-dependent activation of PI-3K/Akt and regulation of Bcl-2 family members. Blood. 2005;105:3169–77.

Article  CAS  PubMed  Google Scholar 

Mizugishi K, Yamashita T, Olivera A, Miller GF, Spiegel S, Proia RL. Essential role for sphingosine kinases in neural and vascular development. Mol Cell Biol. 2005;25:11113–21.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kloska A, Malinowska M, Gabig-Ciminska M, Jakobkiewicz-Banecka J. Lipids and lipid mediators associated with the risk and pathology of ischemic stroke. Int J Mol Sci. 2020;21:3618.

Purroy F, Ois A, Jove M, Arque G, Sol J, Mauri-Capdevila G, et al. Lipidomic signature of stroke recurrence after transient ischemic attack. Sci Rep. 2023;13:13706.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang XX, Li L, Jiang RH, Yu JB, Sun YQ, Shan J, et al. Lipidomic analysis identifies long-chain acylcarnitine as a target for ischemic stroke. J Adv Res. 2024;61:133–49.

Article  CAS  PubMed  Google Scholar 

ElAli A, Doeppner TR, Zechariah A, Hermann DM. Increased blood-brain barrier permeability and brain edema after focal cerebral ischemia induced by hyperlipidemia: role of lipid peroxidation and calpain-1/2, matrix metalloproteinase-2/9, and RhoA overactivation. Stroke. 2011;42:3238–44.

Article  CAS  PubMed  Google Scholar 

Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010;119:7–35.

Article  PubMed