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Objective:To investigate the effects of fasudil hydrochloride(FH) on Rho-associated kinase 2(ROCK2) protein and ferroptosis in hippocampal area during early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Total 36 SPF grade Sprague-Dawley rats were divided into 3 groups by random number table method: Sham group, SAH group and SAH+ FH (a ROCK2 protein inhibitor) group (FH goup) with 12 rats in each group.SAH animal model was established by internal carotid artery perforation.The rats in FH group were injected intraperitoneally with FH(15 mg/kg) 30 minutes after successful modeling, and rats in Sham group and SAH group were injected intraperitoneally with the same volume of 0.9% sodium chloride solution.Twenty-four hours after the intervention, shuttle box test was used to observe the learning and memory ability of rats.The Fe 2+ content in rat hippocampus tissue was detected by colorimetry, and the protein levels of ROCK2 and ferroptosis-related long-chain acyl-CoA synthetase 4(ACSL4) and glutathione peroxidase 4(GPX4) in hippocampus were detected by immunohistochemistry and Western blot.Statistical analysis was performed by SPSS 20.0 software.One-way ANOVA was used for multigroup comparison, and LSD test was used for further pairwise comparison. Results:(1)In the shuttle box test, there were statistically significant differences in the number of avoidance reactions and avoidance reaction time of rats among the three groups( F=20.348, 22.316, both P<0.05). The number of avoidance reaction in SAH group was less than that in Sham group ((17.92±2.94) times, (27.13±3.48) times, P<0.05), the time of avoidance reaction in SAH group was longer than that in Sham group ((9.15±2.87) s, (3.68±1.09) s, P<0.05), while the number of avoidance reaction in FH group ((21.63±4.11) times) was more than that in SAH group, and the time of avoidance reaction ((6.08±1.76) s) was shorter than that in SAH group (both P<0.05). (2) The colorimetry results showed that there was a statistically significant difference in the content of Fe 2+ in hippocampus of rats among the three groups( F=7.965, P<0.05). The Fe 2+ content in SAH group was significantly higher than that of Sham group((0.091±0.032) nmol/mg, (0.038±0.024) nmol/mg, P<0.05), and the Fe 2+ content in the FH group ((0.065±0.021) nmol/mg) was lower than that of SAH group ( P<0.05). (3) There were significant differences in the number of ROCK2, ACSL4 and GPX4 positive cells in hippocampus of rats among the three groups in immunohistochemistry ( F=7.602, 14.171, 36.077, all P<0.05). The positive cells of ROCK2 and ACSL4 in SAH group ((21.63±4.72), (55.13±19.41)) were significantly higher than those of Sham group ((11.63±3.62), (23.38±3.74)) (both P<0.05), and the positive cells of ROCK2 and ACSL4 in FH group ((15.88±6.64), (44.75±8.29)) were both lower than those of SAH group(both P<0.05), while the number of GPX4 positive cells in SAH group (25.38±6.30) was significantly lower than that of Sham group (60.25±10.36) ( P<0.05), and the number of GPX4 positive cells in FH group (45.13±7.51) was higher than that of SAH group( P<0.05). (4)The results of Western blot showed that there were significant differences in the expression levels of ROCK2, ACSL4 and GPX4 proteins in the hippocampus of rats among the three groups( F=4.812, 12.573, 10.849, all P<0.05). The protein expression levels of ROCK2 and ACSL4 in SAH group were significantly higher than those in Sham group(both P<0.05), and the protein expression levels of ROCK2 and ACSL4 in FH group were lower than those in SAH group (both P<0.05), while the expression level of GPX4 protein in SAH group (0.27±0.09) was significantly lower than that in Sham group( P<0.05), and the expression level of GPX4 protein in FH group was higher than that of SAH group ( P<0.05). Conclusion:FH can inhibit ferroptosis in the hippocampus and improve the learning and memory ability of rats, and the mechanism may be related with down-regulation of ROCK2 protein.
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Objective To investigate the effects of fasudil hydrochloride on learning and memory, and the autophagy in hippocampal CA1 neurons in subarachnoid hemorrhage (SAH) rats. Methods Fifty-four male Sprague-Dawley rats were randomly divided into sham group (n=18), SAH group (n=18) and drug group (n=18). Subarachnoid hemorrhage model was established with internal carotid artery punc-ture. The drug group was injected fasudil hydrochloride 10 mg/kg intraperitoneally after modeling per 24 hours, while the sham group and SAH group were injected the same volume of saline. They were tested with shuttle box test 6, 24 and 72 hours after intervention, then the hippocampal CA1 area was stained with HE and immunohistochemistry to observe the morphology of cells and the expression of Beclin-1 and microtubule-associated protein 1 light chain 3 II (LC3-II). Results Compared with the sham group, the frequence of avoidance de-creased in SAH group at each time point (P<0.05), while the avoidance reaction time increased (P<0.05);the survival of neurons in hippo-campal CA1 area decreased (P<0.05), and the expression of Beclin-1 and LC3-II increased (P<0.05). Compared with SAH group, the fre-quence of avoidance increased in the drug group at each time point (P<0.05), while the avoidance reaction time decreased (P<0.05);the sur-vival of neurons in hippocampal CA1 area increased (P<0.05) and the expression of Beclin-1 and LC3-II increased further (P<0.05). Con-clusion Fasudil hydrochloride can improve learning and memory ability and protect neurons from damage, which may associate with the ex-cess of autophagy activation in hippocampal CA1 areas in SAH rats.
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Objective To analyze the intervention effect of the dose-dense schemes of temozolomide on the newly diagnosed glioblastoma compared with the standard schemes. Methods The Pubmed,Cochrane,Em-base,CNKI,CBM,Wanfang,VIP databases were used for the retrievals on the intervention effect.The quality of included papers was assessed to extract network meta-analysis data with using the statistical software Stata 13.0. Results The treatment plans were ranked according to the intervention effect from the best to the worst as follows:the dose-dense,the early,the metronomic,the standard,the RT and post-RT adjuvant temozolomide. The most common adverse effects in hematotoxicity were neutropenia,leucopenia,lymphopenia,thrombocytopenia and ane-mia. Between the different temozolomide therapeutic regimens,there was no significant difference. Conclusion The intervention effect of the dose-dense schemes with temozolomide is better than the standard therapy. It also revealed that,the hematoxicity in the different temozolomide schemes is not significantly different.
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Objective To evaluate the efficacy and safety of radiotherapy combined with concurrent and then adjuvant temozolomide in the patient with glioblastoma.Methods The databases of PubMed,Cochrane library,Medline and OVID were retrieved according to the Cochrane systematical assessment method.The included literatures were performed the quality evaluation and the meta analysis was performed after extracting the data.Results The summary of comparison between temozolomide group and radiotherapy group in the included studies showed that the 12-month overall survival rate[RR 1.22,95 ％ CI(1.01,1.47),P=0.04]and 24-month overall survival rate[RR 2.65,95 ％ CI(1.53,4.40),P＜0.01]had statistically significant differences;the 12-month pregrossion free survival rate[RR 2.59,95 ％CI(1.53,4.40),P=0.000 4] and 24-month pregrossion free survival rate[RR 6.77,95 ％ CI (2.82,16.26),P＜ 0.01] also showed statistically significant difference.The results of adverse reaction events revealed that the hematological toxic reactions in the temozolomide group had statistical difference between the concurrent therapy period and radiotherapy period [RR 3.21,95％CI(1.89,5.46),P＜0.01];which in the temozolomide group had statistical difference between the concurrent period and adjuvant period [RR 0.48,95 ％ CI(0.36,0.65),P＜0.01);but the non-hematological toxic reaction had no statistical difference[RR 1.11,95％CI(0.72,1.70),P=0.64].Conclusion Radiotherapy combined with concurrent and then adjuvant temozolomide therapy improves the overall and progression free survival period in the patient with glioblastoma,the higher occurrence rate of hematologic toxic reactions is correlated with temozolomide treatment drugs.
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Objective To report a newly developed method and procedure to establish a rat model of subarachnoid hemorrhage in detail, and to provide a better model simulating the clinical subarachnoid hemorrhage caused by a ruptured aneurysm for related research.Methods One hundred and twenty healthy SPF 2-3-month old male Sprague-Dawley rats were divided into 4 groups, 30 rats in each group.The three experimental groups were sacrificed at 6, 24 and 72 hours after modeling.Rat models of subarachnoid hemorrhage were established by inserting a fiber core in the internal carotid artery and piercing this artery.Successful establishment of the subarachnoid hemorrhage model was confirmed by observation of breathing, pupil, defecation, urination and inspection at autopsy dissection.The controllability and reproducibility of this model were verified by observation of clinical manifestation and explored by mortality analysis.Results Subarachnoid hemorrhage was successfully induced by fiber core piercing the internal carotid artery at the needed location.Conclusions This method of model preparation is stable and understandable.The operation is nimble, with a good reproducibility.This model can be successfully performed after a short time learning, well simulate the sudden hemorrhage caused by a ruptured aneurysm, and suitable for research on early brain injury and vasospasm after subarachnoid hemorrhage.
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Objective To evaluate the curative effect and safety of mild hypothermia on patients with traumatic brain injury. Methods According to the cochrane systematic review methods , the data bases such as Cochrane, Pubmed, Embase, CBM, CNKI, Wanfang and VIP database were searched. The quality of included documents were assessed to extract meta analysis data. Results Compared to the control group, there was no statistically significant difference in patients treated by hypothermia for 3 days or less in mortality , but the difference was statistically significant after the summary [RR=0.74, 95%CI 0.64~0.85,P<0.000 1]; And there was no statistically significant difference in improving neural function of patients treated by hypothermia for < 3 days , but hypothermia improves the prognosis after the summary [RR=1.40,95%CI 1.24~1.59,P<0.000 01]. The difference was statistically significant in the incidence of pneumonia (P=0.007), there was no statistically significant difference in the incidence of arrhythmia (P=0.06), but the difference was statistically significant after sensitivity analysis. Conclusions Patients treated by hypothermia for < 3 days is not valid for clinical outcomes , the duration of the treament up to 3 days may not reduce mortality rates, but can improve the prognosis, lasts longer than 3 days or until the pressure back to normal, reducing the mortality rate, improve the neurological prognosis;but increased incidence of pneumonia, whether to increase the rate of cardiac arrhythmias have yet to be determined.
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Objective To explore safety evaluation of the approaches of the percutaneous eilational tracheostomy(PDT)ane traeitional tracheotomy in the treatment of neurological patients. Methods The stuey eesign was a multicenter,prospective,raneomizee clinical trial. One huneree ane seventy-six cases with acute nerve trachea incision from Feb. 2010 to Feb. 2013 of 3 hospitals were selectee as our subject. They were raneomly eivieee into the traeitional group ane PDT group. The information inclueing operation time,the incieence of pneumothorax,subcutaneous emphysema,tracheal fistula,esophageal,trachea ane lung injury from complications such as infection were recoreee. Results The complication rate in traeitional group was 19. 51%(16 / 82),higher than that of PDT group(8. 51%(8 / 94),P = 0. 021). The surgery perioe in PDT group was(7. 5 ± 2. 3)min,shortee than that in traeitional group((41. 6 ± 5. 8)min,P = 0. 000). Conclusion The approach of percutaneous tracheostomy can quickly buile airway of neurological patients with character of simple, safe,ane it also can reeuce the incieence of respiratory complications.
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Objective Mild hypothermia provides protection for the brain and improves prognosis in the treatment of severe traumatic brain injury, which is widely acknowledged.The article aimed to analysis the prognosis and complications of long-term and short-term mild hypothermia on patients with severe traumatic brain injury. Methods According to the cochrane systematic review methods, thorough search was carried out in databases including Cochrane, Pubmed, Embase, CBM, CNKI, Wanfang and VIP.Eval-uation was made on the quality of selected documents, and Revman5.2 software was applied for meta analysis after data extraction. Results Long-term mild hypothermia achieved improved prognosis compared to short-term mild hypothermia ( GOS score 4 ~5 ) [RR=1.37, 95%CI (1.14, 1.64), P=0.0006].No significant difference was found between these two therapies in pneumonia in-cidence (P=0.94), arrhythmia incidence ( P=0.54) and stress ulcer incidence (P=0.99). Conclusion In comparison to short-term hypothermia therapy, long-term mild hypothermia therapy improved the prognosis of patients with severe traumatic brain inju-ry without obvious increase in the incidence of pneumonia, arrhythmia and stress ulcer.
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Objective To investigate the efficacy and strategy of percutaneous laser disc decompression (PLDD) for patients with multisegmental lumbar disc herniation. Methods Between December 2005 and December 2008,a total of 56 patients with multisegmental lumbar disc herniation underwent PLDD. Under local anesthesia, the operation was performed using Nd:YAG laser. A digital subtraction angiography (DSA) system was employed to guide the surgery,insert burning, each 1 s, pulse intermission gasification 1 s, single segment laser total 400-800 J. In preoperative and postoperative 3 months visual analogue scale(VAS) and Oswestry disability index (ODI) scores of times during followed up,Macnab standard to assess the clinical curative effect. Results The patients were followed up for 6 - 36 months (mean 18 months). The ODI improved from (31.10 ±2.92) scores to (11.80 ±2.62) scores (t=3.067,P ＜0.01 ). The VAS also showed postoperative improvement of pain compared with preoperative findings (7.00 ± 1.41 ) scores vs (3.00 ± 0.81 ) scores (t= 2.802,P ＜0.01 ). According to the Macnab standard, 36 patients achieved excellent outcomes, 10 were good, 8 were fair, and 2 were poor. The rate of excellent and good outoomes was 82. 1% (46/56). No patient had postoperative complications. Conclusions PLDD is effective and safe for patients with multisegmental lumbar disc berniation. The cases recover quickly after the operation, because the procedure is minimally invasive.