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Objective:To investigate the effect of regional cerebral oxygen saturation (rSO 2) combined with neurophysiological blood pressure monitoring on brain protection and myocardial protection during carotid endarterectomy (CEA) in patients with carotid stenosis and coronary heart disease. Methods:One hundred patients with carotid artery stenosis complicated with coronary heart disease treated in Jinhua Central Hospital from June 2021 to June 2022 were randomly divided into control group and experimental group. All patients were scheduled to undergo CEA. Fifty patients in the control group were administered with empirically increasing basic blood pressure by 20% - 30%, and 50 patients in the experimental group were administered with blood pressure under the guidance of rSO 2 combined with motor evoked potentials (MEPs) and somatosensory evoked potentials (EPS). The neurological function indexes of the two groups [neuron specific enolase (NSE), central nerve specific protein (S100-β)], myocardial function indicators [cardiac troponin I (cTnI), B-type natriuretic peptide (BNP)], clinical indicators (eye opening time, extubation time, recovery room stay time, hospital stay) and the incidence of postoperative complications [delirium (POD), cognitive dysfunction (POCD), neurological impairment] were compard between the two groups. Results:Two sets of postoperative NSE and S100-β both increased ( P<0.05), but NSE and S100 in the experimental group after surgery were lower than those in the control group: (0.82 ± 0.14) μg/L vs. (1.18 ± 0.28) μg/L, (290.13 ± 27.25) mg/L vs. (301.98 ± 28.56) mg/L, the differences were statistically significant ( P<0.05). After surgery, cTnI and BNP increased in both groups ( P<0.05), but the cTnI and BNP in the experimental group were lower than those in the control group: (2.87 ± 0.74)] μg/L vs. (3.36 ± 0.83) μg/L, (3.01 ± 0.85) μg/L vs. (3.89 ± 0.92) μg/L, the differences were statistically significant ( P<0.05). The opening time, extubation time, recovery room stay time, and hospitalization time in the experimental group were shorter than those in the control group: (16.79 ± 3.15) min vs. (20.55 ± 3.83) min, (29.38 ± 4.66) min vs. (40.14 ± 4.57) min, (66.82 ± 15.80) min vs. (89.35 ± 24.78) min, (11.24 ± 4.89) d vs. (14.56 ± 6.74) d, there were statistical differences ( P<0.05). The incidence of postoperative complications in the experimental group was lower than that in the control group: 12.00% (6/50) vs. 28.00% (14/50), there was statistical difference ( P<0.05). Conclusions:The application of rSO 2 combined with neurophysiological blood pressure monitoring in CEA of patients with carotid artery stenosis and coronary heart disease has a good effect, which has brain protection and myocardial protection, can shorten the recovery time of anesthesia and hospitalization time, and reduce the incidence of postoperative complications.
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Objective:To investigate the effects of different doses of dexmedetomidine on intestinal mucosal barrier function, cognitive function and brain protection in patients undergoing heart valve replacement.Methods:The clinical data of 135 patients with heart valve replacement from April 2019 to April 2020 in the First Affiliated Hospital of Chengdu Medical College were retrospectively analyzed. Among them, 54 patients received low-dose of dexmedetomidine after induction of anesthesia (low-dose group), 38 patients received high-dose of dexmedetomidine (high-dose group), and 43 patients did not use dexmedetomidine (control group). Before surgery (T 1), 1 h after surgery (T 2), end of surgery (T 3) and 72 h after surgery (T 4), the levels of intestinal mucosal barrier function indexes D-lactate and diamine oxidase (DAO) were detected by spectrophotometry, the levels of brain injury indexes central nervous system specific protein (S100β) and neuron-specific enolase (NSE) were detected by double antibody sandwich enzyme-linked immunosorbent assay; before surgery and 3 d after surgery, the cognitive function was assessed by the mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) scale before and 3 days after surgery. Result:There was no statistical difference in T 1, T 2 and T 4 D-lactic acid among 3 groups ( P>0.05); the T 3 D-lactic acid in low-dose group was significantly lower than that in high-dose group and the control group: (7.87 ± 1.59) mg/L vs. (8.99 ± 1.82) and (9.32 ± 1.74) mg/L, the high-dose group was significantly lower than the control group, and there were statistical differences ( P<0.05). There was no statistical difference in T 1 and T 2 DAO among 3 groups ( P>0.05); the T 3 and T 4 DAO in low-dose group was significantly lower than that in high-dose group and control group: (2.77 ± 0.23) kU/L vs. (3.58 ± 0.25) and (4.30 ± 0.26) kU/L, (2.08 ± 0.25) kU/L vs. (2.40 ± 0.20) and (2.71 ± 0.23) kU/L, the high-dose group was significantly lower than the control group, and there were statistical differences ( P<0.05). There were no statistical differences in MMSE score and MoCA score before surgery among 3 groups ( P>0.05); the MMSE score and MoCA score 3 d after surgery in low-dose group were significantly higher than those in high-dose group and control group: (22.76 ± 0.54) scores vs. (21.41 ± 0.47) and (20.21 ± 0.43) scores, (24.90 ± 0.51) scores vs. (24.01 ± 0.48) and (23.12 ± 0.49) scores, the high-dose group was significantly higher than the control group, and there were statistical differences ( P<0.05). There was no statistical difference in T 1, T 2 and T 4 S100β among 3 groups ( P>0.05); the T 3 S100β in low-dose group was significantly lower than that in high-dose group and control group: (4.09 ± 2.01) μg/L vs. (5.48 ± 1.10) and (6.10 ± 1.58) μg/L, and there were statistical differences ( P<0.05). There was no statistical difference in T 1 and T 4 NSE among 3 groups ( P>0.05); the T 2 and T 3 NSE in low-dose group was significantly lower than that in high-dose group and control group: (17.20 ± 4.13) μg/L vs. (20.29 ± 3.77) and (22.35 ± 3.80) μg/L, (19.40 ± 3.92) μg/L vs. (23.46 ± 5.26) and (25.18 ± 5.32) μg/L, and there were statistical differences ( P<0.05). Conclusions:Administration of 0.5 μg/(kg·h) dexmedetomidine during heart valve replacement under cardiopulmonary bypass can reduce intestinal mucosal damage, protect brain against injury in a certain degree, and improve cognitive function.
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To compare the neuroprotective and anti-dementia pharmacological effects of chiral oxiracetam, glutamate and calcium ions were used to establish neuronal injury models in vitro, and the protective effects of chiral oxiracetam on primary neurons were assayed by MTT. Permanent bilateral common carotid artery occlusion (2-VO)-induced rats were randomly divided into sham group, model group, galantamine 3 mg‧kg-1 group, oxiracetam groups (30, 100 and 200 mg‧kg-1), S-oxiracetam groups (30, 100 and 200 mg‧kg-1) and R-oxiracetam 200 mg‧kg-1 group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College. Morris water maze and step-down test were applied to evaluate the cognitive dysfunction induced by cerebral hypoperfusion in rats. Oxiracetam, S-oxiracetam and R-oxiracetam exerted protective effects on primary neuronal damage caused by various stimuli, and oxiracetam and S-oxiracetam showed better neuro-protective effects. Morris water maze and step-down results showed that oxiracetam, S-oxiracetam and R-oxiracetam improved the cognition of 2-VO rats. In summary, S-oxiracetam exerted a better neuro-protective effect than oxiracetam and R-oxiracetam.
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Objective:To introduce the early results of total aortic arch replacement (TAA) without cardiopulmonary bypass (CPB) and without interruption of cerebral blood supply, using the technique of arch branches preferential reconstruction and whole brain perfusion for brain protection.Methods:Between June 2020 and March 2021, a total of 9 Stanford type A aortic dissection patients we performed total arch replacement by using the technique of arch branches preferential reconstruction and whole brain perfusion without cardiopulmonary bypass and without interruption of blood supply to the brain. The method of this reconstruction technique is as follows: A 24F aortic cannula was inserted into the true lumen at the root of the transverse innominate artery (IA) to connect one end of the artery for cardiopulmonary bypass. The access was connected to 14F artery via Y-connector and inserted into IA cavity to maintain blood supply to brain. Without cardiopulmonary bypass, the 10 mm branch of the four branch artificial blood vessel was anastomosed with the innominate artery IA. The perfusion collateral was connected to the second end of the artery of CPB (single pump and double tubes) to continue to supply blood for IA. The left common carotid artery (LCA) and left subclavian artery (LSCA) were reconstructed by the same method. When IA and LCA were anastomosed, the distal blood supply was not interrupted. After the three branches of the aortic arch were anastomosed, we started to turn the machine, then cooled down and blocked the ascending aorta to further complete the operation of the aortic root and arch. During the period of lower body circulatory arrest, the whole brain was perfused with low flow.Results:No intraoperative death or perioperative complications occurred in all patients, and they were discharged smoothly. The cardiopulmonary bypass time was (192.4±58.1) min, the aortic clamping time was (128.3±52.4) min, the lower body circulatory arrest time was (29.1±1.3) min, and the postoperative awake time was (8.2±3.7) h.Conclusion:Off-pump arch branches preferential reconstruction can provide physiological whole brain perfusion, shorten the cardiopulmonary bypass time and aortic occlusion time, and the operation is safe and effective.
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AIM: To investigate the protective effect of ginsenoside Rb1 on brain through Cav-1 in mice with cerebral ischemia-reperfusion injury. METHODS: One hundred and twenty C57/B6 mice were randomly divided into sham operation group, model group, model + ginsenoside Rb1 group, ginsenoside Rb1+ Cav-1 siRNA group, ginsenoside Rb1+siNC group, 24 in each group. The model of cerebral ischemia-reperfusion injury in mice was established by middle cerebral artery occlusion (MCAO). The ginsenoside Rb1 group received intraperitoneally injection of ginsenoside Rb1 (40 mg/kg); the sham operation group and model group were intraperitoneally injected with an equal amount of physiological saline immediately after modeling. For the ginsenoside Rb1+ cav-1 siRNA group and the ginsenoside Rb1+siNC group, cav-1 siRNA and siNC were injected into the lateral ventricle 24 h before molding, respectively, and the other operations were the same as the ginsenoside Rb1 group. The neurobehavioral scores of the mice in each group were measured at 24 h after reperfusion, and the water content of brain tissue, cerebral infarction volume, Cav-1 mRNA and Cav-1, Bcl-2 and Bax protein expressions in the cerebral cortex penumbra were measured in each group. RESULTS:Compared with the sham operation group, the neurobehavioral scores, cerebral infarction volume and brain tissue water content in the model group were significantly increased (P<0.05), and the expressions of Cav-1 mRNA and Cav-1 protein, and the Bcl-2 /Bax ratio were significantly decreased (P<0.05). Compared with the model group, the neurobehavioral scores, cerebral infarction volume and brain tissue water content in the ginsenoside Rb1 group were significantly decreased, and the expressions of Cav-1 mRNA and Cav-1 protein, and the Bcl-2 /Bax ratio were significantly increased (P<0.05). Compared with the ginsenoside Rb1 group, the neurobehavioral scores, cerebral infarction volume and brain tissue water content in the ginsenoside Rb1 + cav-1 siRNA group were significantly increased, and the expressions of Cav-1 mRNA and Cav-1 protein, and the Bcl-2 /Bax ratio were significantly decreased (P<0.05). CONCLUSION: Ginsenoside Rb1 can protects brain for mice with cerebral ischemia-reperfusion injury. After Cav-1 siRNA decreased the expression of Cav-1 protein in the brain tissue of mice, it significantly reverses the cerebral protective effect of ginsenoside Rb1, indicating that Cav-1 protein mediated the cerebral protective effect of ginsenoside Rb1 on cerebral ischemia reperfusion injury mice.
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Objective To summarize the brain protection application experiences of combined internal and external blood shunt technologies for the in-situ three-fenestration revascularization of aortic arch.Methods From Feb 2017 to Jun 2018,8 patients with aortic arch leisons were treated by the in-situ three-fenestration techniques,including 3 aortic dissection,2 aortic aneurysm,3 postoperative TEVAR patients.We adopt the method of internal and external blood shunt technologies for brain protection using the vascular sheath for fenestration combined with carotid shunt tube skills,and using TCD to monitor the blood flow of brain.Results All operations completed successfully,and TCD showed no significant cerebral ischemia when aortic stent was used to cover the three branches of the aorta.The mean time of brain protection was (17.62 ± 6.87) minutes.One patient developed transient cerebral ischemia after surgery,and another one developed cerebral infarction.Conclusions The brain protection strategy of internal bypass combined with external converter technology maintain the brain blood flow,while is simple and feasible,it cannot completely avoid neurological complications.
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OBJECTIVE：To in vestigate the effects of dexmedetomidine （Dex）on SIRT 1/Akt/GSK3β/β-catenin signaling pathway in cerebral injury of sepsis model rats ，and explore the mechanism of its protecitve effect on cerebral injury. METHODS ： A total of 80 male SD rats were randomly divided into sham operation group （Sham group ），sepsis group （CLP group ），CLP+Dex group（10 μg/kg Dex），CLP+Dex+Sirtinol group （10 μg/kg Dex+2 μL/100 g SIRT 1 inhibitor sirtinol ），with 20 mice in each group. Two hours before modeling ，CLP+Dex+Sirtinol group was injected with sirtinol via lateral ventricle. Sepsis model was induced by cecal ligation and perforation in each group （in sham group ，only operation was performed but no ligation was performed）. At 0，3，6 h after modeling ，CLP+Dex group and CLP+Dex+Sirtinol group were given Dex （10 μg/kg） intraperitoneally，Sham group and CLP group were given constant volume of normal saline intraperitoneally. Cerebral tissue water content，Evans blue （EB）content，apoptosis in cerebral cortex ，the levels of IL- 1β and TNF-α in cerebral tissue as well as the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were detected 24 h after last medication. RESULTS ： Compared with Sham group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were increased significantly（P＜0.05），while the protein expression of SIRT 1， p-Akt，p-GSK3β and β-catenin in hippocampus were decreased significantly （P＜0.05）. Compared with CLP group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were decreased significantly in CLP+Dex group （P＜0.05），while the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were increased significantly （P＜0.05）. Sirtinol could significantly reverse the above-mentioned cerebral protection and factor regulation effects of Dex （P＜0.05）. CONCLUSIONS ：Dex can protect the cerebral tissue of sepsis model rats，which may play an anti-inflammatory and anti-apoptotic role by activating SIRT 1/Akt/GSK3β/β-catenin signaling pathway ，so as to reduce cerebral edema ，protect blood-brain barrier and reduce cerebral injury.
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Objective@#To explore the differences in brain protection between anterograde cerebral perfusion(ACP) and retrograde cerebral perfusion(RCP) in aortic arch surgery.@*Methods@#Aortic arch circulatory surgery, ACP and RCP techniques were searched at the Cochrane Library, PubMed, EMBASE, Wanfang Database and the Chinese Biomedical Database from January 2013 to December 2018. Cohort studies were then performed with early postoperative death, transient neurological dysfunction(TND), stroke, and transient ischemic attack(TIA). For each study, data on endpoints in the ACP and RCP groups were used to generate risk ratios(RR) and 95% confidence intervals(CI). The funnel chart was used to test publication bias.@*Results@#A total of 6 692 patients were enrolled in 12 studies, of which 3 902 patients received low-temperature circulatory arrest plus ACP, and 2 790 patients received low-temperature circulatory arrest plus RCP. Summary analysis showed that the early postoperative death(RR=0.83, 95%CI=0.51-1.35, P=0.46), stroke(RR=1.09, 95%CI=0.91-1.31, P=0.33), transient neurological dysfunction(RR=0.81, 95%CI=0.17-3.91, P=0.80) and transient ischemic attack(RR=1.00, 95%CI=0.74-1.34, P=1.00) in both groups were no significant differences(all P>0.05).@*Conclusion@#There are no significant differences in postoperative mortality and neurological dysfunction between antegrade cerebral perfusion and retrograde cerebral perfusion in the aortic arch surgery. Combined with hypothermic circulatory arrest, it can be selected according to the actual situation of aortic arch surgery.
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Objective Mild hypothermia (MHT) can effectively protect the brain in traumatic brain injury (TBI). This study was to investigate the effects of MHT on the calmodulin (CAM) expression and brain edema in the rat model of TBI. Methods Ninety adult SD rats were randomly divided into a sham operation, a normal temperature and an MHT group of equal number. Immediately after TBI, the rats of the MHT group maintained at a rectal temperature of (32 ± 0.5) °C for 6 hours. Modified neurological severity scores (mNSS) were obtained from 6 rats in each group at 1, 3, 5 and 7 days after modeling, and the rest of the animals subjected to brain MRI at 6, 12, 24 and 48 hours and then killed for determination of the CAM gene transcription and protein expression in the brain tissue by real-time PCR, immunohistochemistry and Western blot. Results The mNSSs were significantly higher in the MHT and normal temperature groups than in the sham operation control (P < 0.05) at all time points, neurological severity markedly decreased in the MHT group compared with the normal temperature group (P < 0.05). At 6, 12, 24 and 48 hours, the expression of CAM mRNA was remarkably down-regulated in the MHT group (1.83 ± 0.19, 1.72 ± 0.12, 1.59 ± 0.06 and 1.60 ± 0.07) in comparison with the normal temperature group (2.76 ± 0.25, 2.49 ± 0.18, 2.04 ± 0.14 and 1.65 ± 0.09) (P < 0.05), even lower in the MHT than in the normal temperature group (P < 0.05), but higher in both of the two groups than in the sham operation group (P < 0.05). At 6, 12, 24 and 48 hours, the volume of brain edema was significantly reduced in the MHT group ([32.14 ± 4.52], [36.52 ± 4.10], [42.10 ± 4.38] and [46.25 ± 5.02] mm3) as compared with the normal temperature group ([48.56 ± 5.35], [53.13 ± 6.31], [59.23 ± 6.82] and [62.35 ± 7.25] mm3) (P < 0.05). Conclusion Mild hypothermia can improve the neurological function and reduce the CAM expression and brain edema in the brain tissue of rats with traumatic brain injury, which may be related to the neuroprotective effect of mild hypothermia.
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Objective Few studies are reported on the protective effect of valproic acid (VPA) against traumatic brain injury (TBI) by down-regulating the protein expressions of matrix metalloproteinase-9 (MMP-9) and aquaporin-4 (AQP-4) in the brain tissue. This study aimed to investigate the neuroprotective effects of different doses of VPA against TBI in experimental rats. Methods We randomly divided 100 adult male rats into five groups of equal number, sham operation, TBI model, and low- (30 mg), medium- (150 mg) and high-dose (300 mg) VPA treatment. At 1, 3, 7 and 14 days after modeling by controlled cortex impact, we obtained the modified Neurological Severity Scores (mNSS), measured the VPA concentration in the venous blood, and then killed the rats and harvested the brain tissue for determination of the water content using the dry-wet method and the expressions of MMP-9 and AQP-4 by Western blot and immunohistochemistry. Results At 1, 3, 7 and 14 days after modeling, the mNSSs in the high-dose VPA group were 4.6 ± 1.3, 3.8 ± 1.3, 3.0 ± 0.7 and 1.8 ± 0.8, respectively, significantly lower than 8.4 ± 0.9, 7.0 ± 0.7, 5.8 ± 1.0 and 4.5 ± 1.3 in the TBI group (P < 0.05), decreasing in a time-dependent manner, with statistically significant difference between any two dose groups (P < 0.05). At 1, 3 and 7 days, the water contents in the brain tissue were (76.2 ± 0.7)%, (76.9 ± 1.7)% and (73.9 ± 1.3)% in the high-dose VPA group, significantly lower than (79.6 ± 0.8)%, (82.6 ± 0.8)% and (78.6 ± 0.7)% in the TBI group (P < 0.05), also decreasing in a time-dependent manner, with statistically significant difference between any two dose groups (P < 0.05). At 1 and 3 days, the expressions of MMP-9 and AQP-4 in the brain tissue were markedly down-regulated in the VPA groups in a dose-dependent manner as compared with those in the TBI group (P < 0.05), with statistically significant difference between any two dose groups (P < 0.05), and meanwhile immunohistochemistry showed large numbers of cells with positive expressions of MMP-9 and AQP-4, which were reduced with the increased dose of VPA. Conclusion VPA has a neuroprotective effect against TBI in rats by inhibiting the expressions of MMP-9 and AQP-4 proteins in the brain tissue and alleviating brain edema. Within the range of the doses studied, higher-dose VPA produces a better effect.
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Objective To explore the differences in brain protection between anterograde cerebral perfusion( ACP) and retrograde cerebral perfusion( RCP) in aortic arch surgery. Methods Aortic arch circulatory surgery, ACP and RCP tech-niques were searched at the Cochrane Library, PubMed, EMBASE, Wanfang Database and the Chinese Biomedical Database from January 2013 to December 2018. Cohort studies were then performed with early postoperative death, transient neurological dysfunction(TND), stroke, and transient ischemic attack(TIA). For each study, data on endpoints in the ACP and RCP groups were used to generate risk ratios( RR) and 95％ confidence intervals( CI) . The funnel chart was used to test publication bias. Results A total of 6692 patients were enrolled in 12 studies, of which 3902 patients received low-temperature circula-tory arrest plus ACP, and 2790 patients received low-temperature circulatory arrest plus RCP. Summary analysis showed that the early postoperative death(RR=0. 83, 95％CI=0. 51-1. 35,P=0. 46), stroke(RR=1. 09, 95％CI=0. 91-1. 31, P=0.33),transient neurological dysfunction(RR=0.81, 95％CI=0.17-3.91,P=0.80) and transient ischemic attack(RR=1.00,95％CI=0.74-1.34,P=1.00) in both groups were no significant differences(all P>0.05). Conclusion There are no significant differences in postoperative mortality and neurological dysfunction between antegrade cerebral perfusion and retrograde cerebral perfusion in the aortic arch surgery. Combined with hypothermic circulatory arrest, it can be selected ac-cording to the actual situation of aortic arch surgery.
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Objective To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway in the expression of aquaporin 4 (AQP4) in brain tissue of rats with cardiopulmonary resuscitation (CPR) during mild hypothermia. Methods Forty-eight healthy male Sprague-Dawley (SD) rats were divided into sham operation group, normal temperature group and mild hypothermia group according to random number table method, with 16 in each group. The rat model of cardiac arrest-cardiopulmonary resuscitation (CPR) was established by asphyxia method. The sham operation group only experienced venous catheterization and tracheal intubation. The mild hypothermia group was treated with hypothermia 0.5 hours after restore of spontaneous circulation (ROSC, maintaining esophageal temperature at 32-34 ℃); the normal temperature group was treated at room temperature after ROSC (maintaining esophageal temperature at 36-38 ℃). Brain tissue was harvested at 6 hours after ROSC, and histopathological changes were observed by hematoxylin-eosin (HE) staining. The water content of brain tissue was determined by dry-wet specific gravity method. The protein expressions of phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK), p38MAPK and AQP4 in brain tissue were determined by Western Blot. Results Compared with the sham operation group, the nerve cells in the normal temperature group were reduced in size, cytoplasmic loosening, nuclear pyknosis, and in apoptotic body formation, water content of brain tissue was significantly increased [(83.64±2.53)% vs. (77.95±0.94)%, P < 0.05], the protein expressions of p-p38MAPK, p38MAPK, AQP4 were significantly increased (p38MAPK/β- actin: 1.010±0.217 vs. 0.427±0.090, p-p38MAPK/p38MAPK: 0.451±0.172 vs. 0.191±0.141, AQP4/β- actin: 3.129±0.754 vs. 1.598±0.464, all P < 0.05). Compared with the normal temperature group, the degree of necrosis of nerve cells in the mild hypothermia group was reduced, the water content of brain tissue was significantly decreased [(80.49±2.05)% vs. (83.64±2.53)%, P < 0.05], the protein expression of p38MAPK, p-p38MAPK and AQP4 in brain tissue were significantly decreased (p38MAPK/β- actin: 0.590±0.162 vs. 1.010±0.217, p-p38MAPK/p38MAPK: 0.298±0.076 vs. 0.451±0.172, AQP4/β- actin: 2.061±0.340 vs. 3.129±0.754, all P < 0.05). Conclusion Mild hypothermia may regulate the expression of AQP4 in brain tissue of CPR rats through p38MAPK signaling pathway, and reduce brain edema, thereby exerting brain protection.
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Aim To investigate the effects of sevoflurane postconditioning on oxidative stress and the expression of silent information regulation (SIRT1) and peroxisome proliferator-activated receptor γ coactivator la (PGC-1α) in hippocampus of rats subjected to hemorrhagic shock and resuscitation. Methods Male SD rats were randomly divided into sham surgery group (Sham group), shock and resuscitation group (Shock group) and 2.4% sevoflurane postconditioning group (Sevo group). The rats in Sevo group were inhaled 2.4% sevoflurane when received resuscitation after hemorrhagic shock, while rats in Sham and Shock group were treated with 95% O2 and 5% CO2 in the corresponding period. MAP and arterial blood gases were measured at TO (start bleeding), Tl (30 min after bleeding),T2 (start resuscitation), and T3 (30 min after resuscitation). After 24h of surgery,rats with successful model were chosen for the detection of various indexes. The content of malonaldehyde (MDA) in hippocampus and the activity of superoxide dismutase (SOD) in mitochondria isolated from hippocampal tissue were detected. Western blot was used to analyze the protein relative expression levels of SIRT1 and PGC-la in hippocampus. Results Compared with Sham group, the content of MDA increased, the activity of SOD decreased, and the expression of SIRT1 and PGC-1α a increased in Shock group (P < 0. 05). Compared with Shock group, the content of MDA decreased, the activity of SOD increased, and the expression of SIRT1 and PGC-1α increased in Sevo group (P < 0. 05). Conclusions Sevoflurane postconditioning can alleviate oxidative stress in hippocampus of a model rat of hemorrhagic shock and resuscitation, which may be correlated with the up-regulation of the protein relative expression levels of SIRT1 and PGC-1α.
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Objective To study the protective effect of Xingnaojing combined with alprostadil on brain after acute ischemic stroke in rats.MethodsSixty patients with acute ischemic stroke were enrolled in zhejiang xin'an international hospital from March 2014 to March 2016.They were randomly divided into control group and treatment group, 30 cases in each group.The control group received conventional treatment plus alprostadil, the treatment group in the control group based on the combination of Xingnaojing treatment.Two groups of patients after treatment, are given nursing intervention, such as routine diet guidance, nutritional support, health education.The levels of serum oxidative stress (MDA), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor (VEGF) were compared between the two groups before and after treatment.The levels of cerebral blood flow (CBFV) were recorded before and after treatment Observe the adverse reactions during treatment.ResultsAfter 14 days of treatment, the NIHSS score of the treatment group was lower than that of the control group and the ADL score was higher than that of the control group.The difference between the two groups was statistically significant (P<0.05).Before treatment, the oxidative stress indexes MDA and Hcy were no significant difference between the two groups.After treatment, the oxidative stress indexes MDA and Hcy were lower than the control group(P<0.05).Before treatment, the levels of VEGF and CBFV in the two groups were no significant difference between the two groups.After treatment, the levels of VEGF and CBFV in the two groups were significantly higher than those in the control group (P<0.05).The adverse reaction rate between the 2 groups was similar, and there was no significant adverse reaction, there was no significant difference between the two groups.ConclusionXingnaojing combined with alprostadil has a certain clinical effect on acute ischemic stroke, and has a good protective effect on brain tissue after reperfusion.
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Objective To preliminarily explore the effects and brain protective mechanism of intermittent hypoxia preconditioning ( IHP) on rats with seizures induced by lithium-pilocarpine ( Li-pilo) .Methods A total of 96 8-week old male Sprague Dawley rats ( clean grade ) were randomly divided into control group , seizure group and four IHP-seizure groups.The animal model of epilepsy was established by intraperitoneal injection of Li-pilo in the seizure group and four IHP-seizure groups (Li-pilo was injected at 1, 3, 7, or 14 days after a 5-day regimen of IHP).Subsequent seizure behavior , the latency period and percentage of generalized seizures were quantitatively evaluated for 240 min and the cognitive function was tested by Morris water maze task , and followed by the detection of hippocampus neuron apoptosis and related protein (BCL-2, Bax, and cleaved-caspase-3) by TUNEL labeling and Western blot, respectively.Results The induced seizure peaked on an average between 50-150 min after Li-pilo administration , scored using a modified Racine scale.The average scores of modified Racine scale in the IHP-3d seizure group was significantly lower than that in the other groups.The latency period and percentage of generalized seizures in the IHP-3d seizure group rats were significantly different from the parameters in the seizure group rats (P0.05).Conclusions The results indicate that IHP treatment may help to decrease the susceptibility to epilepsy by reducing abnormal apoptosis , and has a brain protective effect on the seizure rats .
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Objective To compare the effects of moderate and deep hypothermic circulatory arrest (DHCA) during aortic arch surgery in the adult patients,to offer the evidence for the detection of which temperature provides best brain protection in the subjects who accept the great aortic surgery.Methods A total of 109 patients undergoing the surgery of aortic arch were divided into the moderate hypothermic circulatory arrest group and deep hypothermic circulatory arrest group.We recorded the characters of the patients and their cardiopulmonary bypass time,aortic clamping time,cerebral perfusion time and postoperative recovery time,tracheal intubation time,time of intensive care unit (ICU) and postoperative cognitive dysfunction.Results Patients' characteristics were similar in two groups.All the patients were cured.There were no significant differences in aortic clamping time of each group [(111.4 ± 58.4) min vs.(115.9 ± 16.2) min];selective cerebral perfusion time [(27.4 ± 5.9) min vs.(23.5 ±6.1) min] of the moderate hypothermic circulatory arrest group and deep hypothermic circulatory arrest group.There were significant differences in the cardiopulmonary bypass time[(207.4 ± 20.9) min vs.(263.8 ± 22.6) min],the postoperative recovery time [(19.0 ± 11.1) h vs.(36.8 ± 25.3) h],intubation time [(46.4 ± 15.1) h vs.(64.4 ± 6.0)h];length of ICU [(4.7 ± 1.7) d vs.(8.± 2.3) d],and postoperative cognitive dysfunction of the two groups.Conclusion Compared to the deep hypothermic circulatory arrest,the moderate hypothermic circulatory arrest can provide better brain protection and achieve good clinical results.
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ObjectiveTo observe the effects of different doses of Xuebijing on cerebral cortex apoptosis factors bcl-2 and bax in rats at early stage after cardiopulmonary resuscitation (CPR).Methods Thirty-two healthy SD rats aged 12 weeks were divided into four groups by using a random number table method (each,n = 8); all the rats were intubated through the opening of tracheotomy, and the blood pressure was measured through the left/right femoral artery catheter. Asphyxiation was applied to rats, resulting in cardiac arrest (CA), and then cardiopulmonary resuscitation (CPR) was carried out. After restoration of spontaneous circulation (ROSC), 0.9% normal saline 8 mL/kg, 0.9% normal saline 4 mL/kg + Xuebijing 4 mL/kg, 0.9% normal saline 2 mL/kg + Xuebijing 6 mL/kg and Xuebijing 8 mL/kg were given to model group, Xuebijing low dose group, middle dose group and high dose group respectively. The rat body weight, time of CA, CPR-ROSC time, ROSC ratio and the amounts of dopamine and 0.9% saline used in 24 hours were recorded. The positive protein expression levels of bcl-2 and bax in rat cerebral cortex and the ratio of bcl-2/bax was measured at 24 hours after ROSC.Results Compared with the model group, the amount of 0.9% normal saline (mL: 4.2±1.2, 2.6±1.0, 2.5±1.0 vs. 5.5±1.1,P < 0.05) and of dopamine used in 24 hours (μg: 1865±189, 1376±197, 1215±145 vs. 3526±141,P < 0.05), the levels of positive protein expression of bcl-2 (%: 33.4±4.3, 25.5±4.6, 26.1±4.2 vs. 38.5±5.1), and of bax at 24 hours after ROSC (%: 39.5±4.3, 32.8±3.8, 31.9±3.7 vs. 44.3±5.1) and the ratio of bcl-2/bax (0.87±0.16, 0.72±0.13, 0.71±0.14 vs. 0.89±0.11) was significantly decreased in low, middle and high dose groups (allP < 0.05). Compared with the low dose group, the amount of 0.9% normal saline and dopamine used in 24 hours, protein expression levels of bcl-2 and bax at 24 hours and the ratio of bcl-2/bax in middle dose and high dose groups were all lower than those in low dose group (allP < 0.05).Conclusion Xuebibing 6 mL/kg applied at early stage after CPR in rats may show relatively good protective effect on cerebral cortex.
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In recent years, remote ischemic preconditioning is found as a novel way to protect the brain, which may be achieved through nerve pathways, humoral factors or nerve-humoral interaction. The molecular mechanisms for the protection might be related to mitochondria ATP-sensitive potassium channel, mitogen-activated protection kinase, mammalian target of rapamycin, including nitric oxide synthase and cannabinoid receptors. The aim of this review is to explain the mechanism of action of remote ischemic preconditioning on brain protection, as well as the possible direction of clinical application.
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Objective To study the protective effect of erythropoietin (EPO) on brain tissue with cardiac arrest-cardiopulmonary resuscitation (CA-CPR) and its mechanism.Methods 120 male Sprague-Dawley (SD) rats were randomly divided into three groups (each n =40),namely:sham group,routine chest compression group,and conventional chest compression + EPO group (EPO group).The rats in each group were subdivided into CA and 6,12,24,48 hours after restoration of spontaneous circulation (ROSC) five subgroups (each n =8).The model of CA was reproduced according to the Hendrickx classical asphyxia method followed by routine chest compression,and the rats in sham group only underwent anesthesia,tracheostomy intubation and venous-puncture without asphyxia and CPR.The rats in EPO group were given the routine chest compression + EPO 5 kU/kg (2 mL/kg) after CA.Blood sample was collected at different time points of intervention for the determination the content of serum S100 β protein by enzyme linked immunosorbent assay (ELISA).All the rats were sacrificed at the corresponding time points,and the hippocampus was harvested for the calculation of the number of S100 β protein positive cells,and to examine the pathological changes and their scores at 24 hours after ROSC by light microscopy.Results With prolongation of ROSC time,the serum levels of S100 β protein (μg/L) in the routine chose compression group and the EPO group were significantly elevated,peaking at 24 hours (compared with CA:305.7 ± 29.2 vs.44.4 ± 6.2 in routine chest compression group,and 276.7±28.9 vs.44.7±5.6 in the EPO group,both P ＜ 0.05),followed by a fall.The levels of S100β protein at each time point after ROSC in EPO group were significanthy lower than those of the routine chest compression group (83.2 ± 7.5 vs.114.3 ± 15.3 at 6 hours,123.9 ± 20.2 vs.184.9 ± 22.2 at 12 hours,276.7 ± 28.9 vs.305.7 ± 29.2 at 24 hours,256.3 ± 26.6 vs.283.2 ± 23.6 at 48 hours,all P ＜ 0.05).With the prolongation of ROSC time,the S100 β protein positive cell number in brain (cells/HP) in the routine chest compression group and the EPO group was significantly increased,peaking at 24 hours (compared with CA:14.3±2.2 vs.6.7±0.7 in the routine chest compression group,11.3± 1.3 vs.6.8±0.9 in the EPO group,both P ＜ 0.05),then it began to fall.The S100 β protein positive cell number in brain at each time point after ROSC in the EPO group was significantly lower than that of the routine chest compression group (7.0±0.9 vs.7.9± 1.9 at6 hours,8.4± 1.1 vs.10.2±2.2 at 12 hours,11.3± 1.3 vs.14.3±2.2 at24 hours,8.3±0.8 vs.10.8±2.0 at48 hours,all P ＜ 0.05).Under the light microscope,a serious brain cortex injury was found after reproduction of the model,and the degree of injury was reduced after EPO intervention.The pathological score at 24 hours after ROSC in EPO group was lower than that of routine chest compression group (3.83±0.73 vs.4.17±0.75,P ＜ 0.05).Conclusions The S100β protein level in serum and brain tissue was increased early in asphyxia CA-CPR rats.EPO intervention can reduce the expression of S100 protein and reduce the degree of brain injury.
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Objective To assess the feasibility,safety,and effectiveness of early rapid icy normal saline infusion to attain mild hypothermia in cardiac arrest patients. Methods A single-center prospective randomized controlled trial was conducted. From March 2011 to October 2013,patients who had recovery of spontaneous circulation (ROSC)after cardiopulmonary resuscitation (CPR)in Beijing Daxing District People's Hospital were randomly divided into two groups. In icy normal saline group,patients received a rapid infusion of 1 000 mL of 4 ℃ normal saline intravenously to attain a mild hypothermia. In the control group,the patients were treated with ice bag on head,and axillary temperature was monitored. For all patients,rectal temperature was measured and recorded immediately and 1 hour later . The occurrence of pulmonary edema on initial chest X-ray at 6 hours ,occurrence of tremor within 48 hours,ventricular fibrillation recurring within 48 hours,and consciousness or death within 14 days were recorded. Results A total of 45 patients were enrolled,including 23 patients in icy normal saline group and 22 in control group. The patients in icy normal saline group had a rectal temperature descended from(36.7±0.9)℃to(34.9±0.7)℃1 hour later,while the patients in control group had a rectal temperature risen from(36.5±1.0)℃to(37.9±0.9)℃1 hour later. There was significant difference in rectal temperature between two groups (t=2.228,P=0.031). The number of patients who successfully awaken within 14 days in ice normal saline group was significantly larger than that in control group (13 cases vs. 7 cases,χ2=65.710,P=0.021). There was no statistical difference in the occurrence of acute pulmonary edema (4 cases vs . 6 cases),tremor (2 cases vs . 0 case),ventricular fibrillation recurrence (4 cases vs. 5 cases)and death within 14 days (11 cases vs. 12 cases,all P>0.05). Conclusions The study shows that early rapid i.v. infusion of 4℃normal saline is feasible,safe and effective for cerebral resuscitation.