Ischemia/reperfusion (I/R) injury is the leading cause of death following
cardiac arrest (CA) and
cardiopulmonary resuscitation (
CPR). γδT cells are suggested to aggravate blood-brain barrier (BBB) injury in various
pathological processes. We herein investigate the effects of γδT cells inhibitor (UC7-13D5) against I/R injury post-CA/
CPR. C57BL/6 mice were subjected to CA through injection of KCL (70 μL of 0.5 mol/L) and cessation of
mechanical ventilation followed by
CPR. Flow cytometry was performed to measure the proportion of CD3-positive cells after
intraperitoneal injection of 200 μg UC7-13D5 at 6 h, 24 h, and 48 h post-
resuscitation into mice. Neurological scores and modified neurological severity scores were assessed to examine neurological functions.
Brain edema was estimated via brain water content measurements. Immunohistochemistry of
caspase-3 and immunofluorescence staining of
claudin-1, ZO-1 and CD31 were performed to detect neuronal apoptosis, BBB integrity and angiogenesis. Microvascular morphology in the cortical area was assessed via H&E staining. Oxidative stress was determined by measuring
malondialdehyde,
myeloperoxidase,
xanthine oxidase,
superoxide dismutase, and
glutathione peroxidase activities. Western blotting was performed to measure the
protein levels of Nuclear factor-E2-related factor 2 (Nrf2) and
Heme oxygenase-1 (HO-1). UC7-13D5 effectively depleted γδT cells. Inhibition of γδT cells improved neurological deficits and reduced
brain edema post-CA/
CPR. γδT cells depletion attenuated neuronal apoptosis, BBB disruption and oxidative stress and promoted angiogenesis following CA/
CPR. Inhibition of γδT cells facilitated the activation of the Nrf2/HO-1 pathway in CA/
CPR-induced mice. Inhibition of γδT cells alleviates neurological deficits and
cerebral edema in mice with CA/
CPR by inhibiting neuronal apoptosis, BBB disruption and oxidative stress, and promoting angiogenesis via activation of the Nrf2/HO-1 pathway.