N-Methyl-D-Aspartate Receptors Antagonist Prevents Secondary Ischemic Brain Injury Associated With Lipopolysaccharide-Induced Sepsis-Like State Presumably via Immunomodulatory Actions
Copyright © 2022 Taheri, Sardari, Hermann and Sepehri..
Infection is a major reason for poor stroke outcomes, and sepsis is a major cause of stroke-elated deaths. We herein examined whether NMDA receptor blockade, which was reported to exert anti-inflammatory actions, protects against the deleterious consequences of lipopolysaccharide (LPS)-induced sepsis-like state in adult male NMRI mice exposed to transient intraluminal middle cerebral artery occlusion (MCAO). At 24 h post-ischemia, vehicle or Escherichia coli LPS (2 or 4 mg/kg) was intraperitoneally administered, whereas 30 min later vehicle or ketamine (10 mg/kg), which is a non-competitive NMDA receptor antagonist, was intraperitoneally applied. Delivery of LPS at a dosage of 4 mg/kg induced a sepsis-like state characterized by a rectal temperature reduction by ∼4.0°C, increased neurological deficits in Clark score, cylinder and open-field tests, increased brain infarct volume and reduced neuronal survival in the previously ischemic tissue. Notably, additional treatment with ketamine (10 mg/kg) significantly attenuated the sepsis-associated rectal temperature reduction by ∼1.5°C, reduced neurological deficits, reduced infarct volume, and promoted neuronal survival. Ketamine alone did not influence infarct volume or neurological deficits. Real-time PCR data analysis showed that GFAP, CD86, CD206, IL-1β, and IL-10 mRNA levels were significantly increased in ischemic brains of LPS-treated compared with vehicle-treated mice. Additional treatment with ketamine significantly decreased IL-1β and IL-10, but not GFAP, CD86, and CD206 mRNA levels. Our data show that ketamine at a dose that on its own does not confer neuroprotection reverses the adverse effects of LPS-induced sepsis-like state post-ischemia, presumably via immunomodulatory actions.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2022 |
---|---|
Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
---|---|
Enthalten in: |
Frontiers in cellular neuroscience - 16(2022) vom: 01., Seite 881088 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Taheri, Golnar [VerfasserIn] |
---|
Links: |
---|
Themen: |
Focal cerebral ischemia |
---|
Anmerkungen: |
Date Revised 16.07.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
---|
doi: |
10.3389/fncel.2022.881088 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM341909548 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM341909548 | ||
003 | DE-627 | ||
005 | 20231226012844.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3389/fncel.2022.881088 |2 doi | |
028 | 5 | 2 | |a pubmed24n1139.xml |
035 | |a (DE-627)NLM341909548 | ||
035 | |a (NLM)35669105 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Taheri, Golnar |e verfasserin |4 aut | |
245 | 1 | 0 | |a N-Methyl-D-Aspartate Receptors Antagonist Prevents Secondary Ischemic Brain Injury Associated With Lipopolysaccharide-Induced Sepsis-Like State Presumably via Immunomodulatory Actions |
264 | 1 | |c 2022 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Revised 16.07.2022 | ||
500 | |a published: Electronic-eCollection | ||
500 | |a Citation Status PubMed-not-MEDLINE | ||
520 | |a Copyright © 2022 Taheri, Sardari, Hermann and Sepehri. | ||
520 | |a Infection is a major reason for poor stroke outcomes, and sepsis is a major cause of stroke-elated deaths. We herein examined whether NMDA receptor blockade, which was reported to exert anti-inflammatory actions, protects against the deleterious consequences of lipopolysaccharide (LPS)-induced sepsis-like state in adult male NMRI mice exposed to transient intraluminal middle cerebral artery occlusion (MCAO). At 24 h post-ischemia, vehicle or Escherichia coli LPS (2 or 4 mg/kg) was intraperitoneally administered, whereas 30 min later vehicle or ketamine (10 mg/kg), which is a non-competitive NMDA receptor antagonist, was intraperitoneally applied. Delivery of LPS at a dosage of 4 mg/kg induced a sepsis-like state characterized by a rectal temperature reduction by ∼4.0°C, increased neurological deficits in Clark score, cylinder and open-field tests, increased brain infarct volume and reduced neuronal survival in the previously ischemic tissue. Notably, additional treatment with ketamine (10 mg/kg) significantly attenuated the sepsis-associated rectal temperature reduction by ∼1.5°C, reduced neurological deficits, reduced infarct volume, and promoted neuronal survival. Ketamine alone did not influence infarct volume or neurological deficits. Real-time PCR data analysis showed that GFAP, CD86, CD206, IL-1β, and IL-10 mRNA levels were significantly increased in ischemic brains of LPS-treated compared with vehicle-treated mice. Additional treatment with ketamine significantly decreased IL-1β and IL-10, but not GFAP, CD86, and CD206 mRNA levels. Our data show that ketamine at a dose that on its own does not confer neuroprotection reverses the adverse effects of LPS-induced sepsis-like state post-ischemia, presumably via immunomodulatory actions | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a focal cerebral ischemia | |
650 | 4 | |a ischemic stroke | |
650 | 4 | |a neuroinflammantion | |
650 | 4 | |a neurological deficits | |
650 | 4 | |a sepsis | |
700 | 1 | |a Sardari, Maryam |e verfasserin |4 aut | |
700 | 1 | |a Hermann, Dirk M |e verfasserin |4 aut | |
700 | 1 | |a Sepehri, Houri |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Frontiers in cellular neuroscience |d 2007 |g 16(2022) vom: 01., Seite 881088 |w (DE-627)NLM18392083X |x 1662-5102 |7 nnns |
773 | 1 | 8 | |g volume:16 |g year:2022 |g day:01 |g pages:881088 |
856 | 4 | 0 | |u http://dx.doi.org/10.3389/fncel.2022.881088 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 16 |j 2022 |b 01 |h 881088 |