LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

Abstract

Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases.

Retracted: RNA interference‐mediated silencing of S100B improves nerve function recovery and inhibits hippocampal cell apoptosis in rat models of ischemic stroke

“…An elevation in brain water content and MDA levels, along with a decline in SOD activity were observed in the NC, MCAO, and blank groups, while all the results were entirely opposite for the siRNA‐S100B group. Abundant studies have shown that patients with ischemic stroke have increased brain water content, which can result in brain edema . SOD is a brain antioxidant enzyme whose activity plays a crucial role in the diagnosis of ischemic stroke but decreases after ischemic stroke, as demonstrated by Vani et al MDA is a crucial biomarker of lipid peroxidation, which forms when the cellular membrane disrupts after leaking into blood and extracellular space, thus exacerbating IS .…”

“…Abundant studies have shown that patients with ischemic stroke have increased brain water content, which can result in brain edema. 27,28 SOD is a brain antioxidant enzyme whose activity plays a crucial role in the diagnosis of ischemic stroke but decreases after ischemic stroke, as demonstrated by Vani et al 29 MDA is a crucial biomarker of lipid peroxidation, 30 which forms when the cellular membrane disrupts after leaking into blood and extracellular space, thus exacerbating IS. 31 Our results were also consistent with a report published by Nejad et al, suggesting that MDA level is considerably higher in patients with ischemic stroke.…”

Dietary teasaponin ameliorates alteration of gut microbiota and cognitive decline in diet-induced obese mice

“…Therefore, the systemic accumulation of toxins, induced by a HF diet may contribute to inflammation in the hippocampus. It has been reported that activated microglial cells release pro-inflammatory cytokines IL-1 and TNF-α, which contribute to the neurodegenerative process 46 . The activation of astrocytes is known to induce innate and adaptive immunity 47 and astroglial responses were assessed in the present study by GFAP immunostaining.…”

Alpinia oxyphylla Miq extract reduces cerebral infarction by downregulating JNK-mediated TLR4/T3JAM- and ASK1-related inflammatory signaling in the acute phase of transient focal cerebral ischemia in rats

“…Post-ischemic inflammation, one of the main pathological features in the early stage of cerebral I/R injury, contributes to the release of pro-inflammatory mediators, which exacerbate cerebral infarction [ 39 ]. Studies have reported that TLR4 expressed on microglia and astrocytes plays a crucial role in the generation of pro-inflammatory cytokines in the initial stage of cerebral I/R injury, whereas pharmacological interventions alleviate cerebral infarction by inhibiting TLR4-mediated microglial and astrocytic activation in the ischemic area in the acute phase of transient MCAo [ 40 ].…”