Efficacy of phosphocreatine pre-administration on XIAP and Smac in ischemic penumbra of rats with focal cerebral ischemia reperfusion injury

Abstract

Purpose: To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemiareperfusion injury (CIRI). Methods: A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B [intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model], and group C [intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model]. After 24 h for reperfusion, the neurological function was evaluated and the tissue was sampled to detect expression of XIAP, Smac and caspase-3 positive cells in the ischemic penumbra so as to observe the apoptosis. Results: Compared with group B, neurological deficit scores, numbers of apoptotic cells, expression of Smac,caspase-9 and the numbers of Caspase-3 positive cells were decreased while expression of XIAP were increased in the ischemic penumbra of group C. Conclusions: Phosphocreatine pre-administration may elicit neuroprotective effects in the brain by increasing expression of X-linked inhibitor of apoptosis protein, reducing expression of second mitochondia-derived activator of caspase, and inhibiting the apoptosis in the ischemic penumbra.

Assessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies

“…Seven out of 10 individual adult studies, all in rodents, administered creatine before HI. Of these, 4 used dietary supplementation (0.5–2%) for between 4 weeks and 10 days before HI [ 30 , 32 , 33 , 34 ], 2 studies used IV infusion between 60 and 30 min before HI [ 36 , 37 ], and 1 used intra-peritoneal creatine but the timing of administration before HI was not specified [ 31 ]. Six out of 7 studies reported that creatine was associated with neuroprotection.…”

“…Of these, 1 study assessed outcomes immediately after HI [ 33 ], 4 studies assessed outcomes between 1 and 3 days after HI [ 31 , 32 , 36 , 37 ] and 4 studies assessed outcomes at 4-7 days after HI [ 29 , 30 , 35 ]. Five studies reported improvements in histological and functional outcomes [ 29 , 30 , 31 , 32 , 37 ], 1 reported improved histological outcomes but no improvement in function [ 29 ], 2 assessed neuropathology alone [ 35 , 36 ] and 1 assessed functional outcomes alone by measuring oxidative metabolism using magnetic resonance spectroscopy (MRS) [ 33 ]. One study reported no significant improvement in neuropathology immediately after HI using diffusion weighted MRI [ 34 ].…”

“…None of the adult studies reported assessing outcomes in both sexes. Five of nine adult studies used male subjects [ 29 , 30 , 31 , 33 , 34 ], one used females [ 32 ], and three studies did not report the sex of the subjects [ 35 , 36 , 37 ].…”

MicroRNA‐130a regulates neurological deficit and angiogenesis in rats with ischaemic stroke by targeting XIAP

“…A, Neurological function scores in each group; B, Spatial learning and memory function (latency and times of crossing the platforms) of rats in each group; C, Water content of brain tissue in each group; D, HE staining of brain tissues in each group (× 400); E, Comparisons of TTC staining and infarction ratio in the brain tissues in each group; F, Comparisons of TUNEL staining and the apoptotic index in the brain tissues in each group of rats (× 400); G, Expression of Caspase-3, Bax and Bcl-2 detected by Western blot analysis; H, Detection of proliferation and differentiation of endogenous NSCs in the brain tissues by double-labelling immunofluorescence assay as well as its statistics analysis; I, Expression of neurotrophic factors (BDNF and NGF) in the brain tissues in each group; J, Evaluation of microvessel density in the brain infarction area by immunofluorescence staining; K, Expression of VEGF and HGF in the brain tissues in each group; # P < 0.05 vs the MCAO + miR-130a inhibitors group. The results were expressed as mean ± standard deviation and comparisons among groups by one-way ANOVA, followed by Tukey's post hoc test XIAP is declined in rats suffering from cerebral ischaemia reperfusion injury, 28 and a previous study has clarified that XIAP protein levels were decreased in both sexes after stroke. 15 Additionally, this study showed that miR-130a inhibited XIAP expression, and XIAP was a target gene of miR-130a.…”

16S rRNA gene sequencing and LC-MS-based metabolomics show that ischemic stroke is related to gut microbiota and metabolome in rats

“…A total of 17 rats were housed at the animal center of the First Hospital of Hunan University of Chinese Medicine (Changsha, China) at 25 °C, 45-65% humidity, and with water and food available ad libitum. The rats were used to construct a middle cerebral artery occlusion (MCAO) model of cerebral ischemia-reperfusion injury as previously described [10,17,18]. All rats were randomly divided into 2 experimental groups, the IS group and control group.…”