Neuroprotective effects of cold-inducible RNA-binding protein during mild hypothermia on traumatic brain injury

Cold-inducible RNA-binding protein（CIRP）, a key regulatory protein, could be facilitated by mild hypothermia in the brain, heart and liver. This study observed the effects of mild hypothermia at 31 ± 0.5℃ on traumatic brain injury in rats. Results demonstrated that mild hypothermia suppressed apoptosis in the cortex, hippocampus and hypothalamus, facilitated CIRP m RNA and protein expression in these regions, especially in the hypothalamus. The anti-apoptotic effect of mild hypothermia disappeared after CIRP silencing. There was no correlation between mitogen-activated extracellular signal-regulated kinase activation and CIRP silencing. CIRP silencing inhibited extracellular signal-regulated kinase-1/2 activation. These indicate that CIRP inhibits apoptosis by affecting extracellular signal-regulated kinase-1/2 activation, and exerts a neuroprotective effect during mild hypothermia for traumatic brain injury.

Mild hypothermia combined with a scaffold of Ng Rsilenced neural stem cells/Schwann cells to treat spinal cord injury

Because the inhibition of Nogo proteins can promote neurite growth and nerve cell differentiation, a cell-scaffold complex seeded with Nogo receptor （NgR）-silenced neural stem cells and Schwann cells may be able to improve the microenvironment for spinal cord injury repair. Previous studies have found that mild hypothermia helps to attenuate secondary damage in the spinal cord and exerts a neuroprotective effect. Here, we constructed a cell-scaffold complex consisting of a poly（D,L-lactide-co-glycolic acid） （PLGA） scaffold seeded with NgR-silenced neural stem cells and Schwann cells, and determined the effects of mild hypothermia combined with the cell-scaffold complexes on the spinal cord hemi-transection injury in the T9 segment in rats. Compared with the PLGA group and the NgR-silencing cells ＋ PLGA group, hindlimb motor function and nerve electrophysiological function were dearly improved, pathological changes in the injured spinal cord were attenuated, and the number of surviving cells and nerve fibers were increased in the group treated with the NgR-silenced cell scaffold ＋ mild hypothermia at 34℃ for 6 hours. Furthermore, fewer pathological changes to the injured spinal cord and more surviving cells and nerve fibers were found after mild hypothermia therapy than in injuries not treated with mild hypothermia. These experimental results indicate that mild hypothermia combined with NgR gene-silenced cells in a PLGA scaffold may be an effective therapy for treating spinal cord injury.

The pathways by which mild hypothermia inhibits neuronal apoptosis following ischemia/reperfusion injury

Several studies have demonstrated that mild hypothermia exhibits a neuroprotective role and it can inhibit endothelial cell apoptosis following ischemia/reperfusion injury by decreasing casp- ase-3 expression, It is hypothesized that mild hypothermia exhibits neuroprotective effects on neurons exposed to ischemia/reperfusion condition produced by oxygen-glucose deprivation. Mild hypothermia significantly reduced the number of apoptotic neurons, decreased the expres- sion of pro-apoptotic protein Bax and increased mitochondrial membrane potential, with the peak of anti-apoptotic effect appearing between 6 and 12 hours after the injury. These findings indicate that mild hypothermia inhibits neuronal apoptosis following ischemia/reperfusion injury by protecting the mitochondria and that the effective time window is 6-12 hours after ischemia/reperfusion injury.

Mild hypothermia for treatment of diffuse axonal injury: a quantitative analysis of diffusion tensor imaging

Fractional anisotropy values in diffusion tensor imaging can quantitatively reflect the consistency of nerve fibers after brain damage, where higher values generally indicate less damage to nerve fibers. Therefore, we hypothesized that diffusion tensor imaging could be used to evaluate the effect of mild hypothermia on diffuse axona[ injury. A total of 102 patients with diffuse axonal injury were randomly divided into two groups： normothermic and mild hypothermic treatment groups. Patient＇s modified Rankin scale scores 2 months after mild hypothermia were significant- ly lower than those for the normothermia group. The difference in average fractional anisotropy value for each region of interest before and after mild hypothermia was 1.32-1.36 times higher than the value in the normothermia group. Quantitative assessment of diffusion tensor imaging indicates that mild hypothermia therapy may be beneficial for patients with diffuse axonal injury.

Mild hypothermia effects on matrix metalloproteinase-9 expression in the perihematomal region of rats following experimental intracerebral hemorrhage

BACKGROUND： Matrix metalloproteinase-9 （MMP-9） expression increases with intracerebral hemorrhage, and participates in the pathophysiological processes of secondary brain injury after intracerebral hemorrhage. OBJECTIVE： To investigate the effects of mild hypothermia on MMP-9 expression and brain edema in the perihematomal region of experimental intracerebral hemorrhage rats. DESIGN, TIME AND SETTING： The randomized, controlled experiment was performed at the Central Laboratory of Shandong Provincial Hospital between May and September 2007. MATERIALS： Seventy-two, Wistar, male rats, 12-weeks old, were used for this study. Rabbit anti-MMP-9 primary antibody was purchased from Boster, China. METHODS： Wistar rats were equally and randomly divided into normothermia and mild hypothermia groups. The two groups each comprised control, 6-hour intracerebral hemorrhage, 24-hour intracerebral hemorrhage, 48-hour intracerebral hemorrhage, 72-hour intracerebral hemorrhage, and l-week intracerebral hemorrhage subgroups, with six rats in each subgroup. Rat models of intracerebral hemorrhage were established by injecting 100 μL of autologous blood into the rat caudate nucleus. Rats in the mild hypothermia group received four hours of local mild hypothermia immediately following the injection. lntracerebral temperature was maintained at （33 ± 0.5） ℃. Subsequently, intracerebral temperature was spontaneously recovered at 25 ℃. Rats in the control subgroup were not injected with autologous blood and received only with intracerebral hemorrhage. MAIN OUTCOME MEASURES： Brain water content and MMP-9 expression surrounding the hematoma region. RESULTS： MMP-9 expression increased at 6 hours, and brain edema reached a peak at 48 hours after intracerebral hemorrhage. MMP-9 expression was significantly decreased in the mild hypothermia group compared with the normothermia group at each time point （P 〈 0.05）. CONCLUSION： Mild hypothermia can significantly inhibit MMP-9 overexpression and relieve brain edema following intracerebral hemorrhage.

Mild hypothermia in improving multiple organ dysfunction after cardiac arrest

BACKGROUND： Resuscitation after cardiac arrest （CA） with a whole-body ischemia–reperfusion injury causes brain injury and multiple organ dysfunction （MODS）. This study aimed to determine whether mild systemic hypothermia could decrease multiple organ dysfunctions after resuscitation from cardiac arrest.METHODS： The patients who had been resuscitated after cardiac arrest were reviewed. During the resuscitation they had been assigned to undergo therapeutic hypothermia （target temperature, 32°C to 34°C, measured in the rectum） over a period of 24 to 36 hours or to receive standard treatment with normothermia. Markers of different organ injury were evaluated for the ？ rst 72 hours after recovery of spontaneous circulation （ROSC）.RESULTS： At 72 hours after ROSC, 23 patients in the hypothermia group for whom data were available had favorable neurologic, myocardial, hepatic and pulmonic outcomes as compared with 26 patients in the normothermia group. The values of renal function were not signi？ cantly different between the two groups. However, blood coagulation function was badly injured in the hypothermia group.CONCLUSION： In the patients who have been successfully resuscitated after cardiac arrest, therapeutic mild hypothermia can alleviate dysfunction after resuscitation from cardiac arrest.

Effects of mild hypothermia on the expression of microtubule-associated protein 2 in neurons of the hippocampal dentate gyrus in a rat model of cerebral ischemia/reperfusion

BACKGROUND： It is widely accepted that mild hypothermia can protect against injury to cerebral ischemia/reperfusion. OBJECTIVE： To observe the effects of mild hypothermia on microtubule-associated protein 2 （MAP2） expression in the hippocampal dentate gyms in rats following cerebral ischemia/reperfusion. Also, to study neuronal ultrastmctural changes in the dentate gyms to investigate the mechanism of the protection against injury to cerebral ischemia/reperfusion conferred by mild hypothermia. DESIGN, TIME AND SETTING： This randomized grouping, neural cell morphology trial was performed at the Laboratory Animal Center of Yijishan Hospital between March and June 2007. MATERIALS： Eighty-five healthy male Sprague Dawley rats were randomly allocated to three groups： mild hypothermia （n = 40）, normothermia （n = 40）, and sham-operated （n = 5）. METHODS： Cerebral ischemia/reperfusion injury was induced by the suture method in the mild hypothermia and normothermia groups, with a threading depth of 180.5 mm. In the sham-operated group, the suture was inserted 15 mm, with no vascular ligafion, and was followed by reperfusion 2 hours later. In the sham-operated and normothermia groups, the rat rectal temperature was maintained at 36-37 ℃ ; in the mild hypothermia group, it was controlled at 32-33 ℃. MAIN OUTCOME MEASURES： The hippocampal dentate gyms was serially sectioned for hematoxylin-eosin staining and MAP2 immunohistochemistry. Ultrastructural changes and the MAP2 absorbance value of the hippocampal dentate gyms were examined by transmission electron microscopy. RESULTS： The sham-operated group exhibited approximately normal ultrastructure of neurons in the bilateral hippocampal dentate gyms. In the normothermia group, ischemic hippocampal dentate gyms neurons were found with markedly fewer normal mitochondria, greatly proliferated rough endoplasmic reticulum, and a swollen and dysmorphic Golgi. In the mild hypothermia group, at each corresponding time point, these abnormal changes were noticeably alleviated. The number of necrotic mitochondria, as well as the degree of degeneration, was obviously reduced compared with the normothermia group. At days 6, 8 and 10 following reperfusion, the normothermia group exhibited lower neurological function scores than the mild hypothermia group （P 〈 0.05）. In the normothermia group, the absorbance value of MAP2 expression in the ischemic hippocampal dentate gyms was significantly decreased compared with the sham-operated group （P 〈 0.01 ）, was slightly increased at 4 days, and reached a peak on day 8. The mild hypothermia group showed an absorbance value of MAP2 expression in the ischemic hippocampal dentate gyms similar to the normothermia group, but it reached a peak on day 6. On days 1, 2, 4 and 6 following repeffusion, MAP2 expression was lower in the mild hypothermia group than in the sham-operated group, but it was higher than the normothermia group （P 〈 0.05）. CONCLUSION： Mild hypothermia applied in early ischemia can alleviate brain injury. This may be due to an enhancement of MAP2 expression.

Therapeutic benefits of mild hypothermia in patients successfully resuscitated from cardiac arrest:A meta-analysis

BACKGROUND:Good neurological outcome after cardiac arrest(CA) is hard to achieve for clinicians.Experimental and clinical evidence suggests that therapeutic mild hypothermia is beneficial.This study aimed to assess the effectiveness and safety of therapeutic mild hypothermia in patients successfully resuscitated from CA using a meta-analysis.METHODS:We searched the MEDLINE(1966 to April 2012),OVID(1980 to April 2012),EMBASE(1980 to April 2012),Chinese bio-medical literature & retrieval system(CBM)(1978 to April 2012),Chinese medical current contents(CMCC)(1995 to April 2012),and Chinese medical academic conference(CMAC)(1994 to April 2012).Studies were included if 1) the study design was a randomized controlled trial(RCT);2) the study population included patients successfully resuscitated from CA,and received either standard post-resuscitation care with normothermia or mild hypothermia;3) the study provided data on good neurologic outcome and survival to hospital discharge.Relative risk(RR) and 95%confidence interval(CI) were used to pool the effect.RESULTS:The study included four RCTs with a total of 417 patients successfully resuscitated from CA.Compared to standard post-resuscitation care with normothermia,patients in the hypothermia group were more likely to have good neurologic outcome(RR=1.43,95%CI 1.14-1.80,P=0.002) and were more likely to survive to hospital discharge(RR=1.32,95%CI 1.08-1.63,P=0.008).There was no significant difference in adverse events between the normothermia and hypothermia groups(P>0.05),nor heterogeneity and publication bias.CONCLUSION:Therapeutic mild hypothermia improves neurologic outcome and survival in patients successfully resuscitated from CA.

Mild hypothermia effects on intercellular adhesion molecule-1 and serum interleukin-6 expression in brain tissues of a rat focal ischemia model

BACKGROUND： Previous studies have confirmed the neuroprotective effect of mild hypothermia on ischemic brain injury. OBJECTIVE： To investigate the effects of mild hypothermia on intercellular adhesion molecule-1 expression and serum interleukin-6 levels in ischemic brain tissues of focal brain ischemia rats, and to explore the neuroprotective effects of mild hypothermia on ischemic brain injury. DESIGN, TIME AND SETTING： A randomized, controlled, neurobiological experiment was performed at the Central Laboratory, First Affiliated Hospital, Xinxiang Medical College, China from February to July 2006. MATERIALS： Thirty healthy, adult, Sprague Dawley rats were used to establish middle cerebral artery occlusion models using the suture method, The immunohistochemistry （streptavidin-biotin-peroxidase complex method） kit was purchased from Boster, China. Interleukin-6 radioimmunoassay was supplied by Institute of Radioimmunity, Technology Development Center, General Hospital of Chinese PLA. METHODS： The rats were equally and randomly assigned into mild hypothermia and control groups, and middle cerebral artery occlusion models were established. The rectal temperature was maintained at （37 ±0.5）℃ in the control group. In the mild hypothermia group, the rectal temperature was maintained at （33±1）℃. MAIN OUTCOME MEASURES： At 12 hours after model establishment, the ischemic brain hemispheres were coronally sliced at the level of the optic chiasm. The number of intercellular adhesion molecule-1-positive vessels per high-power field was observed with an optical microscope. Serum interleukin-6 levels were measured by radioimmunoassay. RESULTS： Compared with the control group, intercellular adhesion molecule-1 and serum interleukin-6 expressions were significantly decreased in ischemic brain tissues of the mild hypothermia group （P 〈 0.01）. CONCLUSION： Mild hypothermia exhibits a neuroprotective effect by reducing serum interleukin-6 and intercellular adhesion molecule-1 expression following cerebral ischemia.

Effects of mild hypothermia on the ROS and expression of caspase-3 m RNA and LC3 of hippocampus nerve cells in rats after cardiopulmonary resuscitation

BACKGROUND: Cardiac arrest(CA) is a common and serious event in emergency medicine. Despite recent improvements in resuscitation techniques, the survival rate of patients with CA is unchanged. The present study was undertaken to observe the effect of mild hypothermia(MH) on the reactive oxygen species(ROS) and the effect of neurological function and related mechanisms.METHODS: Sixty-five healthy male Sprague Dawley(SD) adult rats were randomly(random number) divided into 2 groups: blank control group(n=5) and CPR group(n=60). CA was induced by asphyxia. The surviving rats were randomly(random number) divided into two groups: normothermia CPR group(NT) and hypothermia CPR group(HT). Normothermia of 37 °C was maintained in the NT group after return of spontaneous circulation(ROSC), hypothermal intervention of 32 °C was carried out in the HT group for 4 hours immediately after ROSC. Both the NT and HT groups were then randomly divided into 2 subgroups 12 hours and 24 hours after ROSC(NT-12, NT-24, HT-12, HT-24 subgroups). During observation, the neurological defi cit scores(NDSs) was recorded, then the bilateral hippocampi were obtained from rats' head, and monoplast suspension of fresh hippocampus tissue was made immediately to determine the level of intracellular ROS by flow cytometry. Transmission electron microscope was used to observe the ultramicro changes of cellular nucleus and mitochondria. Reverse transcription-polymerase chain reaction(RT-PCR) was used to determine the expression of caspase-3 m RNA, and western-blotting(WB) was used to determine the level of LC3 in frozen hippocampus tissue. Measured data were analyzed with paired sample t test and One-Way ANOVA.RESULTS: Of 60 rats with CA, 44(73%) were successfully resuscitated and 33(55%) survived until the end of the experiment. The NDSs of rats in the NT and HT groups were more signifi cantly reduced than those in the BC group(F=8.107, P<0.05), whereas the NDSs of rats in the HT-12 and HT-24 subgroups were significantly increased in comparison with those NDSs of rats in the NT-12 and NT-24 subgroups, respectively(t=9.692, P<0.001; t=14.374, P<0.001). The ROS in hippocampus nerve cells in the NT and HT groups signifi cantly increased compared to the BC group(F=16.824, P<0.05), whereas the ROS in the HT-12 and HT-24 subgroups significantly reduced compared with that ROS in the NT-12 and NT-24 subgroups, respectively(t=9.836, P<0.001; t=7.499, P<0.001). The expression of caspase-3 m RNA in hippocampus nerve cells in the NT and HT groups were signifi cantly increased compared to the BC group(F=24.527, P<0.05), whereas the expression of caspase-3 m RNA in rats of the HT-12 and HT-24 subgroups was signifi cantly reduced compared to the NT-12 and NT-24 subgroups, respectively(t=6.935, P<0.001; t=4.317, P<0.001). The expression of LC3B-II/I in hippocampus nerve cells of rats in the NT and HT groups signifi cantlyincreased compared to the BC group(F=6.584, P<0.05), whereas the expression of LC3B-II/I in rats of the HT-12 and HT-24 subgroups significantly reduced compared to the NT-12 and NT-24 subgroups, respectively(t=10.836, P<0.001; t=2.653, P=0.02). Ultrastructure damage of nucleus and mitochondria in the NT group was more evident than in the BC group, and eumorphism of nucleus and mitochondria were maintained in rats of the HT group compared with the NT group.CONCLUSION: Mild hypothermia lessened the injury of nerve cells and improved the neurological function of rats that survived from cardiac arrest by reducing the ROS production of nerve cells and inhibiting the expression of caspase-3 m RNA and LC3, leading to cellular apoptosis and massive autophagy in rats that survived from cardiac arrest after CPR.

Combination of mild therapeutic hypothermia and adipose-derived stem cells for ischemic brain injury

Mild therapeutic hypothermia has been shown to mitigate cerebral ischemia, reduce cerebral edema, and improve the prognosis of patients with cerebral ischemia. Adipose-derived stem cell-based therapy can decrease neuronal death and infiltration of inflammatory cells, exerting a neuroprotective effect. We hypothesized that the combination of mild therapeutic hypothermia and adipose-derived stem cells would be neuroprotective for treatment of stroke. A rat model of transient middle cerebral artery occlusion was established using the nylon monofilament method. Mild therapeutic hypothermia（33°C） was induced after 2 hours of ischemia. Adipose-derived stem cells were administered through the femoral vein during reperfusion. The severity of neurological dysfunction was measured by a modified Neurological Severity Score Scaling System. The area of the infarct lesion was determined by 2,3,5-triphenyltetrazolium chloride staining. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end labeling（TUNEL） staining. The regeneration of microvessels and changes in the glial scar were detected by immunofluorescence staining. The inflammatory responses after ischemic brain injury were evaluated by in situ staining using markers of inflammatory cells. The expression of inflammatory cytokines was measured by reverse transcription-polymerase chain reaction. Compared with mild therapeutic hypothermia or adipose-derived stem cell treatment alone, their combination substantially improved neurological deficits and decreased infarct size. They synergistically reduced the number of TUNEL-positive cells and glial fibrillary acidic protein expression, increased vascular endothelial growth factor levels, effectively reduced inflammatory cell infiltration and down-regulated the m RNA expression of the proinflammatory cytokines interleukin-1β, tumor necrosis factor-α and interleukin-6. Our findings indicate that combined treatment is a better approach for treating stroke compared with mild therapeutic hypothermia or adipose-derived stem cells alone.

Hippocampal expression of apoptotic protease activating factor-1 following diffuse axonal injury under mild hypothermia

The influence of mild hypothermia on neural cell apoptosis remains poorly understood. Therefore, the present study established rat models of diffuse axonal injury （DAI） at 33℃. Morris water maze results demonstrated significantly better learning and memory functions in DAI rats with hypothermia compared with DAI rats with normothermia. Expression of apoptotic protease activating factor-1 in the hippocampal CA1 region was significantly lower in the DAI hypothermia group compared with the DAI normothermia group. Expression of apoptotic protease activating factor-1 positively correlated with latency, but negatively correlated with platform location times and time of swimming in the quadrant area. Results suggested that post-traumatic mild hypothermia in a rat model of DAI could provide cerebral protection by attenuating expression of apoptotic protease activating factor-1.

The effect of body weight on the induction of mild hypothermia in a rabbit model of asphyxia cardiac arrest

Objective To investigate the effect of body weight on the induction of mild hypothermia in a rabbit model of asphyxia cardiac arrest. Methods Twenty-four rabbits were randomized into two groups： the ice bag group and the intravenous 4℃ saline group. Cardiac arrest was induced and after 3 minutes of cardiac arrest, cardiopulmonary resuscitation was begun. Simultaneously, mild hypothermia was induced by putting an ice bag over the abdomen or infusion of 4℃ saline via an ear vein. A 2℃ decrease of rectal temperature was considered as the completion of hypothermia induction. Induction times were recorded, compared, and analyzed with respect to body weight. Results All rabbits had restoration of spontaneous circulation （ROSC） and ROSC lasted during the experiment. Induction time in the ice bag group was significantly shorter than that in the intravenous 4℃ saline group （22.8 ± 4.7 min VS 42.5 ± 4.0 min, P〈 0.001）. Induction time significantly correlated with body weight in the ice bag group （Pearson Correlation： r = 0.725, P = 0.029）, but not in the intravenous 4℃ saline group （Pearson Correlation： P = 0.418）. Conclusions In a rabbit model, induction of mild hypothermia with an ice bag is faster than with intravenous 4~C saline; induction time positively correlates with body weight when an ice bag is used, but not when intravenous 4℃ saline used. The effect of body weight should be considered when choosing an appropriate method to achieve early induction of mild hypothermia

EFFECT OF MILD HYPOTHERMIA ON ACTIVITY NITRIC OXIDE SYNTHASE IN CORTICAL NEURONS AND GLYCEMIA LEVELS OF NEONATAL RATS WITH HYPOXIC ISCHEMIC BRAIN DAMAGE

Through investigating the effect of mild hypothermia on activity of nitric oxide snythase (NOS) in cortical neurons and glycemia levels of neonatal rats with hypoxic ischemic brain damage (HIBD). We studied the mechanism of protecting hypoxic ischemic neurons of mild hypothermia. We established neonatal rat HIBD models, used NOS immunohistochemistry and glycemia determination by micromethod. The number of cortical NOS positive neurons after hypoxic ischemia was significantly decreased as compared with controls. The glycemia levels was significantly increased than that controls. No significant difference was found in number of cortical NOS positive neurons and glycemia levels between 31℃ and 34℃ mild hypothemia. The results imply that hypothermia can decrease overproduction of NO through inhibiting the increase of the activity of NOS, and increase the glycemia levels, thus protect the hypoxic ischemic neurons.

不同时程亚低温治疗对重型颅脑损伤患者免疫功能及预后的影响

目的:分析对比不同时程亚低温治疗在重型颅脑损伤(STBI)患者中的效果。方法:选取2020年7月—2023年3月赣南医学院第一附属医院收治的120例STBI患者,按随机数字表法分为三组,各40例。常规组给予脱水、降颅压、去骨瓣减压术基础治疗,对照组在其基础上加以短时程(治疗2 d)亚低温治疗,观察组在常规组基础上加以长时程(治疗5 d)亚低温治疗。对比三组病情严重程度、免疫功能、氧合情况、并发症发生情况及预后。结果:治疗前,三组急性生理学和慢性健康状况评价Ⅱ(APACHEⅡ)评分、CD4^(+)、CD4^(+)/CD8^(+)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、γ干扰素(IFN-γ)、中心静脉血氧饱和度(ScvO_(2)),动-静脉二氧化碳分压差[P(cv-a)CO_(2)]相比,差异均无统计学意义(P>0.05);治疗后,观察组APACHEⅡ评分、IL-6、TNF-α、IFN-γ、P(cv-a)CO_(2)均低于对照组与常规组,CD4^(+)、CD4^(+)/CD8^(+)、ScvO_(2)均高于对照组与常规组,差异均有统计学意义(P<0.05);观察组、对照组并发症发生率、28 d死亡率均低于常规组,差异均有统计学意义(P<0.05);对照组、观察组并发症发生率、28 d死亡率相比,差异均无统计学意义(P>0.05)。结论:长时程亚低温治疗STBI患者效果更佳,可有效控制病情,改善其免疫功能,且并发症发生率与28 d死亡率更低,改善患者预后。

Effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury

To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (sTBI).Methods All 33 patients with sTBI(GCS≤8) were randomly divided into hypothermic group and control group.Microdialysis catheters were inserted into the cerebral cortex of perilesion,relative normal brain tissue and subcutaneous tissue of abdomen in order to analyze the concentrations of lactate/pyruvate (L/P),lactate/glucose (L/G) and the glycerol(Gly) in extracellular fluid (ECF).Results In comparison with the control group,the concentration of L/G,L/P and Gly in periphery and that of L/P in ECF of the “normal brain tissue” were significantly decreased in the hypothermic group.In control group,concentration of L/G,L/P and Gly in periphery were higher than those in relative normal brain.In the hypothermic group,L/P concentration in periphery was higher than that in relative normal brain.Conclusion Mild hypothermia protects brain by decreasing concentrations of L/G,L/P and Gly in periphery and L/P concentration in “normal brain tissue”.The energy crisis and membrane phospholipid breakage in periphery are easier to happen after TBI,where mild hypothermia exerts significant protgective role.12 refs,3 tabs.

血清BDNF在新生儿缺氧缺血性脑病亚低温治疗中的临床价值研究

目的:探讨脑源性神经营养因子(BDNF)在新生儿缺氧缺血性脑病(HIE)亚低温治疗的临床价值。方法:选取2018年5月至2022年4月在天津医科大学第二医院新生儿科无HIE的20名健康婴儿为对照组,接受亚低温治疗的90例HIE患儿为研究组(中度HIE患儿48例,重度HIE患儿42例)。分别于治疗前(生后1 h)、治疗后第3天及第7天测定患儿BDNF、肌酸磷酸激酶(CK)和肌酸激酶同工酶MB(CK-MB)水平及治疗后第3天酸碱度(PH)值、碱剩余(BE)值。结果:BDNF在重度HIE患儿中水平显著高于中度组(t=8.56,P<0.01),中度和重度HIE患儿的亚低温疗效分别为95.8%和66.7%,亚低温治疗后神经异常组或死亡组BDNF水平明显高于改善组。对于中度HIE患儿,亚低温治疗后3 d和7 d与出生后1 h相比,血清CK-MB和CK水平均显著降低(F=66.35、87.06,均P<0.01);重度HIE患儿经亚低温治疗后表现出相同的趋势(F=79.23、138.2,均P<0.01)。对于PH和BE,中度HIE患儿治疗3 d均较生后1 h升高,差异有统计学意义(t=14.05、25.201,均P<0.01);重度HIE患儿治疗后表现出相同的变化趋势(t=16.783、29.17,均P<0.01)。结论:血清BDNF水平可能成为亚低温治疗HIE患儿临床效果新的预测指标。

复方脑肽节苷脂注射液联合亚低温治疗重症颅脑损伤患者的效果

目的:观察复方脑肽节苷脂注射液联合亚低温治疗重症颅脑损伤患者的效果。方法:选取2020年1月至2022年12月该院收治的80例重症颅脑损伤患者进行前瞻性研究,按随机数字表法将其分为对照组与研究组各40例。对照组采用亚低温治疗,研究组在对照组基础上联合复方脑肽节苷脂注射液治疗,比较两组治疗前后认知状态[改良蒙特利尔量表(MoCA)、简易智能精神状态检查表(MMSE)]评分、神经功能缺损程度[美国国立卫生研究院卒中量表(NIHSS)]评分、肢体功能[Fugl-Meyer运动功能量表(FMA)]评分、神经损伤相关指标[降钙素基因相关肽(CGRP)、神经肽Y(NPY)、胶质纤维酸性蛋白(GFAP)]水平,以及不良反应发生率。结果:治疗后,两组MoCA、MMSE评分均高于治疗前,且研究组高于对照组,差异有统计学意义(P<0.05);两组NIHSS评分均低于治疗前,且研究组低于对照组,两组FMA评分均高于治疗前,且研究组高于对照组,差异有统计学意义(P<0.05);两组CGRP水平均高于治疗前,且研究组高于对照组,两组NPY、GFAP水平均低于治疗前,且研究组低于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:复方脑肽节苷脂联合亚低温治疗重症颅脑损伤患者可提高认知状态和肢体功能评分,改善神经损伤相关指标水平,降低神经功能缺损程度评分,其效果优于单纯亚低温治疗。

亚低温疗法联合依达拉奉治疗重症颅脑损伤患儿的临床疗效

目的:探讨亚低温疗法联合依达拉奉治疗重症颅脑损伤(Severe craniocerebral injury,SCCI)患儿的临床疗效,及对患儿神经功能、血液流变学、炎性因子、预后的影响.方法:选取南阳市第一人民医院2019年1月至2022年12月收治的98例SCCI患儿为研究对象,随机数字表法将患儿分为常规组和联合组(n=49),分别进行对症抢救及对症+亚低温疗法联合依达拉奉治疗.治疗2 w后,比较两组临床疗效和不良反应,采用美国国立卫生院卒中评分量表(National Institutes of Health stroke scale,NIHSS)评估患者的神经功能,采用格拉斯哥预后量表(Glasgow outcome scale,GOS)评估患者的预后恢复状况,采用全自动血液流变仪检测患者的血液流变学指标(血浆黏度、全血低切黏度、全血高切黏度、血沉),酶联免疫吸附法检测超敏C反应蛋白(Hypersensitive C-reactive protein,hs-CRP)、白细胞介素-6(Interleukin-6,IL-6)、泛素羧基末端水解酶Ll(Ubiquitin C-terminal hydrolase-L1,UCH-L1)、纤维胶凝蛋白3(Ficolin3,FCN3)水平.结果:治疗2 w后,联合组(93.88%)临床总有效率高于常规组(79.59%)(P<0.05);联合组NIHSS评分低于常规组,GOS评分高于常规组(P<0.05);联合组血浆黏度、全血低切黏度、全血高切黏度、血沉、血清hs-CRP、IL-6、UCH-L1水平明显低于常规组,FCN3水平明显高于常规组(P<0.05);两组不良反应发生率比较,无显著差异(P>0.05).结论:亚低温疗法联合依达拉奉治疗SCCI患儿疗效显著,可有效改善血液流变学,减轻神经损伤,抑制炎症反应,安全性较好.

NLRP3炎性小体在治疗性浅低温后处理大鼠心肌缺血-再灌注中的作用

目的 分析NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体在治疗性浅低温(34℃)后处理的大鼠离体心肌缺血-再灌注模型中的作用并探讨其机制。方法 选择清洁级成年雄性SD大鼠60只,7~10周龄,体重250~300 g。采用随机数字表法将大鼠分为五组:空白对照组(S组)、心肌缺血-再灌注组(IR组)、34℃浅低温后处理心肌缺血-再灌注组(MH组)、34℃浅低温后处理心肌缺血-再灌注+3-TYP组(HT组)和34℃浅低温后处理心肌缺血-再灌注+3-TYP+MCC950组(HTM组),每组12只。S组在37℃灌流液平衡灌流大鼠心脏180 min;IR组在37℃灌流液平衡灌流大鼠心脏30 min后,缺血30 min, 37℃灌注液再灌注120 min;MH组在37℃灌流液平衡灌流大鼠心脏30 min后,缺血30 min, 34℃灌注液再灌注120 min;HT组在37℃灌流液平衡灌流大鼠心脏30 min后,缺血30 min,在灌注液中加入沉默信息调节因子2同源蛋白3(sirt3)抑制剂3-TYP后行34℃灌注液再灌注120 min;HTM组在37℃灌流液平衡灌流大鼠心脏30 min后,缺血30 min,在灌注液中加入sirt3抑制剂3-TYP和NLRP3抑制剂MCC950后行34℃灌注液再灌注120 min。再灌注120 min后取离体心脏,采用ELISA法测定灌注后心脏漏液中IL-1β、IL-6浓度,Western blot法检测心肌组织中NLRP3和sirt3蛋白相对含量,1%氯化三苯基四氮唑染色计算心肌梗死面积,HE染色观察心肌病理变化。结果 与S组比较,IR组、MH组、HT组和HTM组再灌注30、60、90、120 min时HR明显减慢,LVSP、dp/dt_(max)明显降低,LVEDP明显升高;心脏漏液中IL-6和IL-1β浓度、心肌梗死面积百分比明显升高(P<0.05);IR组、HT组和HTM组心肌组织中sirt3蛋白含量明显降低,NLRP3蛋白含量明显升高(P<0.05);MH组心肌组织中sirt3和NLRP3蛋白含量明显升高(P<0.05)。与IR组比较,MH组和HTM组再灌注30、60、90、120 min时HR明显增快,LVSP、±dp/dt_(max)明显升高,LVEDP明显降低;心脏漏液中IL-6和IL-1β浓度、心肌梗死面积百分比明显降低(P<0.05);MH组心肌组织中sirt3蛋白含量明显升高,NLRP3蛋白含量明显降低(P<0.05);HTM组心肌组织中NLRP3蛋白含量明显降低(P<0.05)。与MH组比较,HT组再灌注30、60、90、120 min时HR明显减慢,LVSP、±dp/dt_(max)明显降低,LVEDP明显升高;心脏漏液中IL-6和IL-1β浓度、心肌梗死面积百分比、心肌组织中NLRP3蛋白含量明显升高(P<0.05);HT组和HTM组心肌组织中sirt3蛋白含量明显降低(P<0.05)。与HT组比较,HTM组再灌注30、60、90、120 min时HR明显增快,LVSP、±dp/dt_(max)明显升高,LVEDP明显降低;心脏漏液中IL-6和IL-1β浓度、心肌梗死面积百分比、心肌组织中NLRP3蛋白含量明显降低(P<0.05)。结论 治疗性浅低温(34℃)可通过改善离体心脏血流动力学参数、降低IL-6、IL-1β浓度、心肌组织中NLRP3蛋白含量、心肌梗死面积百分比、改善心肌病理学改变,减轻大鼠心肌缺血-再灌注损伤,其机制可能与线粒体介导sirt3通路抑制炎性小体NLRP3的高表达有关。