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.