title: Telmisartan reduced cerebral edema by inhibiting NLRP3 inflammasome in mice with cold brain injury.
abstract: The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury (TBI) and the potential mechanisms related to the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) pyrin domain-containing 3 (NLRP3) inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier (BBB) integrity, the neurological function and histological injury were assessed, at the same time, the mRNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein (ASC) and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation.
authors.affiliation: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Shang-Long
authors.initials: SL
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. mweike@163.com.
authors.forename: Wei-Ke
authors.initials: WK
authors.lastname: Mao
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage; D001565:Benzoates / Q000008:administration & dosage; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D020170:Caspase 1 / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D058847:Inflammasomes / Q000009:adverse effects / Q000235:genetics; D020382:Interleukin-18 / Q000096:biosynthesis*; D053583:Interleukin-1beta / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D000077333:Telmisartan
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; C587672:IL1B protein, mouse; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D020170:Caspase 1; D000077333:Telmisartan
keywords: NLRP3 inflammasome; cerebral edema; inflammation; telmisartan; traumatic brain injury