{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:33:52Z","timestamp":1790393632083,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Feng Yuan Hospital and the Ministry of Health and Welfare, Taiwan","award":["101"],"award-info":[{"award-number":["101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>In stroke patients, the development of acute kidney injury (AKI) is closely linked with worse outcomes and increased mortality. In this study, the interplay between post-stroke and AKI and treatment options was investigated in a rodent model of hemorrhagic stroke. Intrastriatal collagenase injection for 24 h caused neurological deficits, hematoma formation, brain edema, apoptosis, blood\u2013brain barrier disruption, oxidative stress, and neuroinflammation in Sprague Dawley rats. Elevation of serum blood urea nitrogen, serum creatinine, urine cytokine-induced neutrophil chemoattractant-1, and urine Malondialdehyde, as well as moderate histological abnormality in the kidney near the glomerulus, indicated evidence of kidney dysfunction. The accumulation of podocalyxin DNA in urine further suggested a detachment of podocytes and structural deterioration of the glomerulus. Circulating levels of stress hormones, such as epinephrine, norepinephrine, corticosterone, and angiotensin II were elevated in rats with intracerebral hemorrhage. Osmotic agent glycerol held promising effects in alleviating post-stroke brain injury and kidney dysfunction. Although the detailed protective mechanisms of glycerol have yet to be determined, the intrastriatal collagenase injection hemorrhagic stroke model in rats allowed us to demonstrate the functional and structural integrity of glomerulus are targets that are vulnerable to post-stroke injury and stress hormones could be surrogates of remote communications.<\/jats:p>","DOI":"10.3390\/antiox10040623","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T11:21:38Z","timestamp":1618831298000},"page":"623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Glycerol Improves Intracerebral Hemorrhagic Brain Injury and Associated Kidney Dysfunction in Rats"],"prefix":"10.3390","volume":"10","author":[{"given":"Cheng-Yi","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Surgery, Feng Yuan Hospital, Taichung City 420, Taiwan"},{"name":"Department of Veterinary Medicine, National Chung Hsing University, Taichung City 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-Ho","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, National Chung Hsing University, Taichung City 402, Taiwan"},{"name":"Department of Pediatrics, Tungs\u2019 Taichung Metro Harbor Hospital, Taichung City 435, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Ri","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Urology, Taichung Veterans General Hospital, Taichung City 407, Taiwan"},{"name":"Department of Nursing, HungKuang University, Taichung City 433, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Chuan","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Urology, Tungs\u2019 Taichung Metro Harbor Hospital, Taichung City 435, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Lan","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung City 407, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5105-5285","authenticated-orcid":false,"given":"Wen-Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, National Chung Hsing University, Taichung City 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8991-6394","authenticated-orcid":false,"given":"Yu-Hsiang","family":"Kuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Chung Shan Medical University, Taichung City 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Jung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung City 407, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung City 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"165260","DOI":"10.1016\/j.bbadis.2018.09.012","article-title":"Current advances in ischemic stroke research and therapies","volume":"1866","author":"Barthels","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Arnold, J., Ng, K.P., Sims, D., Gill, P., Cockwell, P., and Ferro, C. (2018). Incidence and impact on outcomes of acute kidney injury after a stroke: A systematic review and meta-analysis. BMC Nephrol., 19.","DOI":"10.1186\/s12882-018-1085-0"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1159\/000499029","article-title":"Incidence, risk factors, and biomarkers predicting ischemic or hemorrhagic stroke associated acute kidney injury and outcome: A retrospective study in a general intensive care unit","volume":"47","author":"Jiang","year":"2019","journal-title":"Blood Purif."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1177\/0271678X19890931","article-title":"Brain-kidney interaction: Renal dysfunction following ischemic stroke","volume":"40","author":"Zhao","year":"2020","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000479338","article-title":"Acute kidney injury following acute ischemic stroke and intracerebral hemorrhage: A meta-analysis of prevalence rate and mortality risk","volume":"45","author":"Ziai","year":"2018","journal-title":"Cerebrovasc. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"104483","DOI":"10.1016\/j.jstrokecerebrovasdis.2019.104483","article-title":"Gastrodin attenuates neuronal apoptosis and neurological deficits after experimental intracerebral hemorrhage","volume":"29","author":"Liu","year":"2020","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"20041","DOI":"10.1074\/jbc.RA118.001858","article-title":"miR-27a-3p protects against blood-brain barrier disruption and brain injury after intracerebral hemorrhage by targeting endothelial aquaporin-11","volume":"293","author":"Xi","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11768","DOI":"10.18632\/aging.103342","article-title":"L-3-n-butylphthalide attenuates inflammation response and brain edema in rat intracerebral hemorrhage model","volume":"12","author":"Zeng","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.brainres.2018.09.012","article-title":"Glutathione peroxidase 4 participates in secondary brain injury through mediating ferroptosis in a rat model of intracerebral hemorrhage","volume":"1701","author":"Zhang","year":"2018","journal-title":"Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s00210-018-1523-3","article-title":"Modulation of brain ACE and ACE2 may be a promising protective strategy against cerebral ischemia\/reperfusion injury: An experimental trial in rats","volume":"391","author":"Messiha","year":"2018","journal-title":"Naunyn. Schmiedebergs Arch. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s11011-015-9749-y","article-title":"Chromium supplementation improved post-stroke brain infarction and hyperglycemia","volume":"31","author":"Chen","year":"2016","journal-title":"Metab. Brain Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"F345","DOI":"10.1152\/ajprenal.00032.2020","article-title":"Endothelial prolyl hydroxylase 2 is necessary for angiotensin II-mediated renal fibrosis and injury","volume":"319","author":"Zhao","year":"2020","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.brainresbull.2017.06.018","article-title":"The effect of monascin on hematoma clearance and edema after intracerebral hemorrhage in rats","volume":"134","author":"Wang","year":"2017","journal-title":"Brain Res. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1111\/jon.12736","article-title":"CT-based classification of acute cerebral edema: Association with intracranial pressure and outcome","volume":"30","author":"Lietke","year":"2020","journal-title":"J. Neuroimaging"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s12028-018-0535-7","article-title":"Mannitol and hypertonic saline reduce swelling and modulate inflammatory markers in a rat model of intracerebral hemorrhage","volume":"29","author":"Schreibman","year":"2018","journal-title":"Neurocrit. Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/iub.1972","article-title":"Ischemic preconditioning improved renal ischemia\/reperfusion injury and hyperglycemia","volume":"71","author":"Li","year":"2019","journal-title":"IUBMB Life"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ejphar.2017.10.021","article-title":"Effect of monoamine oxidase inhibitors on ischaemia\/reperfusion-induced acute kidney injury in rats","volume":"818","author":"Tsutsui","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1161\/01.STR.0000151328.70519.e9","article-title":"Neurochemical monitoring of glycerol therapy in patients with ischemic brain edema","volume":"36","author":"Berger","year":"2005","journal-title":"Stroke"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1080\/01616412.1999.11741015","article-title":"Glycerol attenuates the adherence of leukocytes in rat pial venules after transient middle cerebral artery occlusion","volume":"21","author":"Ishikawa","year":"1999","journal-title":"Neurol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0022-510X(02)00465-3","article-title":"Effect of glycerol on ischemic cerebral edema assessed by magnetic resonance imaging","volume":"209","author":"Sakamaki","year":"2003","journal-title":"J. Neurol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1001\/jamapediatrics.2016.4151","article-title":"Clinical characteristics, risk factors, and outcomes associated with neonatal hemorrhagic stroke: A population-based case-control study","volume":"171","author":"Cole","year":"2017","journal-title":"JAMA Pediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"147007","DOI":"10.1016\/j.brainres.2020.147007","article-title":"Curcumin-loaded nanoemulsion improves haemorrhagic stroke recovery in wistar rats","volume":"1746","author":"Marques","year":"2020","journal-title":"Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1111\/j.1440-1681.2008.04942.x","article-title":"Intraperitoneal glycerol induces oxidative stress in rat kidney","volume":"35","author":"Rieger","year":"2008","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lin, S.Y., Wang, Y.Y., Chang, C.Y., Wu, C.C., Chen, W.Y., Kuan, Y.H., LiaoL, S.L., and Chen, C.J. (2020). Effects of b-adrenergic blockade on metabolic and inflammatory responses in a rat model of ischemic stroke. Cells, 9.","DOI":"10.3390\/cells9061373"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.12659\/MSM.915119","article-title":"Lipoxin A4 methyl ester reduces early brain injury by inhibition of the nuclear factor kappa B (NF-kappaB)-dependent matrix metallopeptidase 9 (MMP-9) pathway in a rat model of intracerebral hemorrhage","volume":"25","author":"Song","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"77","DOI":"10.2147\/NDT.S120496","article-title":"The role of heme oxygenase-1 (HO-1) in the regulation of inflammatory reaction, neuronal cell proliferation and apoptosis in rats after intracerebral hemorrhage (ICH)","volume":"13","author":"Fan","year":"2016","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_27","first-page":"3920","article-title":"MicroRNA-146a protects against intracerebral hemorrhage by inhibiting inflammation and oxidative stress","volume":"18","author":"Qu","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1161\/STROKEAHA.116.014601","article-title":"Renal dysfunction is associated with poststroke discharge disposition and in-hospital mortality: Findings from get with the guidelines-stroke","volume":"48","author":"Fonarow","year":"2017","journal-title":"Stroke"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jstrokecerebrovasdis.2012.06.005","article-title":"Acute kidney injury is associated with increased hospital mortality after stroke","volume":"23","author":"Khatri","year":"2014","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"616","DOI":"10.2215\/CJN.04110808","article-title":"Long-term prognosis of acute kidney injury after first acute stroke","volume":"4","author":"Tsagalis","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7679","DOI":"10.1038\/s41598-019-44194-3","article-title":"Angiotensin II-mediated MYH9 downregulation causes structural and functional podocyte injury in diabetic kidney disease","volume":"9","author":"Kang","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1515\/jpem-2020-0138","article-title":"Role of urinary NGAL and KIM-1 as biomarkers of early kidney injury in obese prepubertal children","volume":"33","author":"Polidori","year":"2020","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1620\/tjem.218.35","article-title":"D-ribose attenuates ischemia\/reperfusion-induced renal injury by reducing neutrophil activation in rats","volume":"218","author":"Sato","year":"2009","journal-title":"Tohoku. J. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1097\/SHK.0000000000000478","article-title":"AP39, a mitochondrially targeted hydrogen sulfide donor, exerts protective effects in renal epithelial cells subjected to oxidative stress in vitro and in acute renal injury in vivo","volume":"45","author":"Ahmad","year":"2016","journal-title":"Shock"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1007\/s00125-012-2661-7","article-title":"Urinary podocalyxin is an early marker for podocyte injury in patients with diabetes: Establishment of a highly sensitive ELISA to detect urinary podocalyxin","volume":"55","author":"Hara","year":"2012","journal-title":"Diabetologia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1159\/000312883","article-title":"Absence of gelatinase (MMP-9) or collagenase (MMP-13) attenuates adriamycin-induced albuminuria and glomerulosclerosis","volume":"115","author":"Sakamaki","year":"2010","journal-title":"Nephron. Exp. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12869","DOI":"10.18632\/aging.103343","article-title":"miR-183-5p alleviates early injury after intracerebral hemorrhage by inhibiting heme oxygenase-1 expression","volume":"12","author":"Wang","year":"2020","journal-title":"Aging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3389\/fnagi.2016.00124","article-title":"Intracranial pressure elevation 24 h after ischemic stroke in aged rats is prevented by early, short hypothermia treatment","volume":"8","author":"Murtha","year":"2016","journal-title":"Front. Aging Neurosci."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/4\/623\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:49:50Z","timestamp":1760161790000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/4\/623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,19]]},"references-count":38,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["antiox10040623"],"URL":"https:\/\/doi.org\/10.3390\/antiox10040623","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,19]]}}}