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Post\u2010cardiac arrest syndrome (PCAS) may be related to an early systemic inflammatory response leading to exaggerated and sustained neuroinflammation. Therefore, early intervention with targeted drug delivery to attenuate neuroinflammation may greatly improve therapeutic outcomes. Using a clinically relevant asphyxia CA model, we demonstrate that a single (i.p.) dose of dendrimer\u2010N\u2010acetylcysteine conjugate (D\u2010NAC), can target \u201cactivated\u201d microglial cells following CA, leading to an improvement in post\u2010CA survival rate compared to saline (86% vs. 45%). D\u2010NAC treatment also significantly improved gross neurological score within 4\u00a0h of treatment (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and continued to show improvement at 48\u2009h (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Specifically, there was a substantial impairment in motor responses after CA, which was subsequently improved with D\u2010NAC treatment (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). D\u2010NAC also mitigated hippocampal cell density loss seen post\u2010CA in the CA1 and CA3 subregions (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). These results demonstrate that early therapeutic intervention even with a single D\u2010NAC bolus results in a robust sustainable improvement in long\u2010term survival, short\u2010term motor deficits, and neurological recovery. Our current work lays the groundwork for a clinically relevant therapeutic approach to treating post\u2010CA syndrome.<\/jats:p>","DOI":"10.1002\/btm2.10259","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T03:50:25Z","timestamp":1631591425000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Systemic administration of dendrimer N\u2010acetyl cysteine improves outcomes and survival following cardiac arrest"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1731-7111","authenticated-orcid":false,"given":"Hiren R.","family":"Modi","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering The Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Brain Trauma Neuroprotection Branch, Center for Military Psychiatry and Neuroscience Walter Reed Army Institute of Research (WRAIR)  Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qihong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Center for Blood Oxygen Transport and Hemostasis (CBOTH), Department of Pediatrics University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah J.","family":"Olmstead","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth S.","family":"Khoury","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nirnath","family":"Sah","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Payam","family":"Gharibani","sequence":"additional","affiliation":[{"name":"Department of Neurology The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rishi","family":"Sharma","sequence":"additional","affiliation":[{"name":"Center for Nanomedicine, Department of Ophthalmology Wilmer Eye Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3712-7836","authenticated-orcid":false,"given":"Rangaramanujam M.","family":"Kannan","sequence":"additional","affiliation":[{"name":"Center for Nanomedicine, Department of Ophthalmology Wilmer Eye Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujatha","family":"Kannan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9981-9395","authenticated-orcid":false,"given":"Nitish V.","family":"Thakor","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resuscitation.2005.03.021"},{"issue":"4","key":"e_1_2_10_3_1","first-page":"e29","article-title":"Heart disease and stroke statistics\u20142015 update: a report from the American Heart Association","volume":"131","author":"Mozaffarian D","year":"2015","journal-title":"Circulation"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000558"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000485"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","unstructured":"SansS KestelootH KromhoutDo ForceT.The burden of cardiovascular diseases mortality in Europe: task force of the European society of cardiology on cardiovascular mortality and morbidity statistics in. 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