Effects of Txk‑mediated activation of NF‑κB signaling pathway on neurological deficit and oxidative stress after ischemia‑reperfusion in rats

Abstract

Ischemic stroke is an extremely mortal cerebrovascular disease, and neuroinflammation and oxidative stress emerge as important traits of ischemic stroke. However, as an inflammation-associated factor, Txk tyrosine kinases (Txk) has been poorly studied in neuroscience research. The aim of the present study was to investigate the role of Txk after ischemia-reperfusion (I/R) in vivo and in vitro , observe the association between Txk knockdown and neurological deficit and oxidative stress, and to explore whether the process was mediated by the activation of nuclear factor (NF)-κB signaling pathway. Middle cerebral artery occlusion (MCAO), oxygen and glucose deprivation/reperfusion (OGD/R) model and western blotting have been used to simulate the I/R injury to analyze the expression, and to approximate the localization of Txk, respectively. Brain infarct volume, neurological score, brain water content, apoptosis and oxidative stress assays in vivo and apoptosis, cellular viability, the LDH release and oxidative stress assays in vitro were observed using a Txk-knockdown lentivirus. Finally, NF-κB overexpression lentivirus was applied to discuss whether the role of Txk following I/R was regulated by the NF-κB signaling pathway. The results show that the Txk expression peaked at 24 h after MCAO and 6 h after OGD/R, respectively. Txk molecules gradually entered the nucleus after MCAO and OGD/R. The Txk-knockdown lentivirus resulted in decreased brain infarct volume, neurological score, brain water content, apoptosis and oxidative stress after MCAO in vivo . Besides, Txk knockdown decreased apoptosis, LDH release, oxidative stress, and increased cellular viability, after ODG in vitro . Finally, NF-κB overexpression reversed the process of neurological deficit and oxidative stress after Txk regulation in vivo and vitro . Overall, the present study suggests that Txk potentially regulates apoptosis, neurological deficit, and oxidative stress after I/R, by entering the nucleus. NF-κB maybe the downstream target factor of Txk.

Neuroprotective Effects of an N-Salicyloyl Tryptamine Derivative against Cerebral Ischemia/Reperfusion Injury

“…After cerebral I/R injury, the generation of ROS increases, creating an imbalance between production and clearance that triggers inflammation and cell death by mutilating proteins, DNA, and RNA . Many antioxidants lessen cerebral I/R injury, strongly suggesting that the regulation of oxidative stress is an appealing prospective therapeutic target for minimizing cerebral I/R injury. , After cerebral I/R damage, oxygen free radicals are created, SOD viability is lowered, and the MDA concentration is raised, leading to lipid peroxidation, which further inhibits nerve cell function and causes brain damage. , It was discovered that administering LZWL02003 to LPS-stimulated microglia inhibited the increase in ROS and, consequently, the inflammatory response . However, no previous research has indicated that LZWL02003 can lessen the oxidative damage induced by cerebral I/R.…”

“…31,32 After cerebral I/R damage, oxygen free radicals are created, SOD viability is lowered, and the MDA concentration is raised, leading to lipid peroxidation, which further inhibits nerve cell function and causes brain damage. 33,34 It was discovered that administering LZWL02003 to LPS-stimulated microglia inhibited the increase in ROS and, consequently, the inflammatory response. 10 However, no previous research has indicated that LZWL02003 can lessen the oxidative damage induced by cerebral I/R.…”

Fermented Mentha arvensis administration provides neuroprotection against transient global cerebral ischemia in gerbils and SH-SY5Y cells via downregulation of the MAPK signaling pathway

“…In transient global cerebral ischemic stroke, sudden cerebral blood flow is occluded, causing a lack of oxygen and glucose supply to brain tissues leading to irreparable neuronal injury [ 4 ]. Transient global cerebral ischemic stroke is a life-threatening cerebrovascular disease in which neuroinflammation and oxidative stress are prominent features [ 5 ].…”

Olanzapine Ameliorates Ischemic Stroke-like Pathology in Gerbils and H2O2-Induced Neurotoxicity in SH-SY5Y Cells via Inhibiting the MAPK Signaling Pathway

“…When this balance is altered by abnormal stimuli, cells may undergo oxidative stress, leading to the production of a huge amount of reactive oxygen species (ROS) by mitochondria [ 6 ]. Excessive production of ROS (including the superoxide radical, O 2 · − ) contributes to neuronal cell damage by disrupting cell membranes, damaging DNA, and triggering cellular apoptosis [ 7 , 8 , 9 ]. Antioxidant superoxide dismutase enzymes (SODs) are able to convert O 2 · − into hydrogen peroxide (H 2 O 2 ) and oxygen (O 2 ).…”