{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:37:04Z","timestamp":1792841824831,"version":"4.5.0"},"reference-count":37,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82060342"],"award-info":[{"award-number":["82060342"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Natural Science Foundation of Ningxia Province","award":["2023A1433"],"award-info":[{"award-number":["2023A1433"]}]},{"name":"Natural Science Foundation of Ningxia Province","award":["2019AAC02003"],"award-info":[{"award-number":["2019AAC02003"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cannabis &amp; Cannabinoid Research"],"published-print":{"date-parts":[[2026,12,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Improving long-term survival rates after cardiac arrest (CA) is an important clinical challenge. The endocannabinoid 2-arachidonoylglycerol (2-AG) exerts endogenous neuroprotective and anti-inflammatory effects; its hydrolysis by monoacylglycerol lipase (MAGL) not only terminates 2-AG signaling but also releases arachidonic acid (AA), a precursor to multiple proinflammatory mediators. We hypothesized that inhibiting MAGL with JZL184 would improve neurological outcomes after CA by increasing the levels of 2-AG and suppressing AA-induced inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      In a clinical cohort, we assess the correlations between plasma endocannabinoid levels and the neurological outcomes of CA patients at 7 days postresuscitation. In rat models of asphyxia-induced CA, the animals were randomly allocated to the Sham, cardiopulmonary resuscitation (CPR), or CPR + JZL184 (16 mg\/kg, intraperitoneal) groups. Within 7 days after the return of spontaneous circulation (ROSC), we assessed survival, neurological deficit scores (NDSs), spatial memory, cerebral edema, cerebral blood volume (CBV) (\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      functional ultrasound), and the levels of key lipid mediators (2-AG, AEA, AA, TXB2, and PGs) in the brain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A favorable outcome was associated with higher 2-AG levels at 6 h and lower AA levels at 1 and 5 days after ROSC among the patients (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.05). In rats, JZL184 treatment significantly increased the 7-day survival rate, improved NDSs and memory function, attenuated cerebral edema, and promoted cerebral microcirculatory recovery (CBV,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.01). Mechanistically, JZL184 robustly increased cerebral 2-AG levels while reducing the levels of AA and its proinflammatory metabolites (TXB2 and PGs,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The MAGL inhibitor JZL184 confers substantial neuroprotection after CA and CPR by modulating the lipid mediator network in the brain. It alleviates cerebral injury and improves survival and neurological recovery primarily by increasing the levels of 2-AG and concurrently suppressing the AA-induced inflammatory cascade.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/25785125261490165","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:03:57Z","timestamp":1790399037000},"page":"439-451","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Monoacylglycerol Lipase Inhibition by JZL184 Improves Neurological Outcomes and Survival after Cardiac Arrest via 2-AG-Mediated Restoration of Cerebral Microcirculation"],"prefix":"10.1177","volume":"11","author":[{"given":"Nan","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, People\u2019s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, People\u2019s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanrong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, People\u2019s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongjie","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, People\u2019s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Cao","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, People\u2019s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenhui","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, People\u2019s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, People\u2019s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Yang","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaozhang","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, People\u2019s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China."},{"name":"Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8937-9143","authenticated-orcid":false,"given":"Kerong","family":"Hai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, People\u2019s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, 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