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.

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.

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.

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.

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.

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.

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 cerebral oxygen metabolism and brain injury in patients with severe craniocerebral injury

Objective: To investigate the effects of mild hypothermia on cerebral oxygen metabolism and brain injury in patients with severe craniocerebral injury. Methods: A total of 78 patients with severe craniocerebral injury who underwent emergency treatment in Huanggang Central Hospital between September 2015 and May 2017 were selected as the research subjects and divided into control group (n=39) and mild hypothermia group (n=39) by random number table. Control group received clinical standard large trauma craniotomy for severe craniocerebral injury, and mild hypothermia group received routine surgery and postoperative mild hypothermia therapy. The cerebral oxygen metabolism and brain injury in two groups of patients were detected immediately after admission (T0), 1 week after treatment (T1) and 4 weeks after treatment (T2). Results: At T0, there was no statistically significant difference in the levels of cerebral oxygen metabolism indexes, cerebral blood flow parameters and brain injury markers between the two groups. At T1 and T2, PO2 levels in mild hypothermia group were higher than those in control group while Da-jvO2 levels were lower than those in control group;cerebral blood flow parameters Vs and Wv levels were higher than those in control group while PI levels were lower than those in control group;brain injury markers MBP, AQP-4 and S-100B contents were lower than those in control group while BDNF contents were higher than those in control group. Conclusion: Adjuvant mild hypothermia therapy after routine surgery may further reduce the cerebral oxygen metabolism and relieve the brain injury in patients with severe craniocerebral injury.

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

Vitamin D_(3) attenuates anxiety-like behavior in long-term ovariectomized rats with unpredictable mild stress

The impact of various vitamin D3(VD3)doses(1.0,2.5,or 5 mg/kg,s.c.)in mitigating the negative consequences of chronic unpredictable mild stress(CUMS)was investigated.Adult female rats with long-term estrogen deficiency were assessed using the sucrose preference test(SPT),the elevated plus-maze(EPM),the light/dark test(LDT),and the open-field test(OFT)to measure anhedonia-like and anxiety-like behavior.The corticosterone(CS)and adrenocorticotrophic hormone(ACTH)concentrations in blood serum and the brain-derived neurotrophic factor(BDNF)expression in the hippocampus of long-term ovariectomized(OVX)rats were measured by ELISA kits and/or western blotting.Treatment with VD3(5.0 mg/kg),similarly to fluoxetine(10.0 mg/kg),significantly reduced the anhedonia profile in the SPT and anxiety-like behavior in the EPM and LDT,and CS and ACTH levels in blood serum.It also elevated BDNF levels in the hippocampus of long-term OVX/CUMS compared to OVX/CUMS/solvent rats.Thus,these findings suggest that VD3(5.0 mg/kg)administration might attenuate the anxiety-like profile in long-term OVX adult rats subjected to the CUMS.This might occur via activation of the BDNF signaling pathway in the hippocampus and via restoration of CS and ACTH levels in blood serum.

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.

Therapeutic effect of phenobarbital combined with mild hypothermia on neonatal asphyxia

Objective: To analyze the efficacy of phenobarbital combined with mild hypothermia in the treatment of neonatal asphyxia. Methods: Subjects selected 50 children with neonatal asphyxia treated in our hospital from February 2016 to August 2017. They were randomly divided into a control group and an observation group with 25 cases in each group. The two groups of children were given routine resuscitation treatment. The control group was given phenobarbital injection on the basis of this. The observation group was given phenobarbital combined with mild hypothermia treatment, the heart rate, respiration, blood pressure changes, liver and kidney function, coagulation function and blood gas analysis after treatment were analyzed and compared between the two groups. At the same time, the outcomes and NBNA scores of the two groups were compared. Results: During the course of treatment, the heart rate of the observation group at the same time period was significantly lower than that of the control group (P<0.05);After treatment, Respiratory, systolic and diastolic blood pressures in two groups of children, serum urea (BUN), serum creatinine (Scr), thromboplastin time (PT), plasma thrombin time (TT), arterial serum pH, blood, There was no significant difference in partial pressure of oxygen (PO2) and remaining alkali (BE) (all P>0.05), the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and NBNA scores in the observation group were significantly higher than those in the control group (all P<0.05), the length of hospitalization and feeding time were significantly lower than those in the control group (all P<0.05). Conclusion: Phenobarbital combined with mild hypothermia for neonatal asphyxia can significantly improve brain damage and liver and kidney function in children, reduce acidosis and respiratory depression, and have no negative effect on heart rate, blood pressure, coagulation function, etc. The efficacy is good and its safety is high.

Clinical study about mild hypothermia + intravenous thrombolysis in promoting the neural functional recovery in patients with acute cerebral infarction

Objective: To explore the efficacy of mild hypothermia + intravenous thrombolysis in promoting the neural functional recovery in patients with acute cerebral infarction. Methods: A total of 176 patients with acute cerebral infarction who were treated in our hospital between September 2015 and February 2017 were reviewed and divided into the routine group (n=100 cases, receiving routine intravenous thrombolysis therapy) and the mild hypothermia group (n=76, receiving mild hypothermia + intravenous thrombolysis therapy), and the treatment lasted for 1 week. The differences in serum levels of nerve injury indexes, inflammatory mediators and neurotransmitters were compared between the two groups before treatment and after 1 week of treatment. Results: Before treatment, there was no statistically significant difference in serum levels of nerve injury indexes, inflammatory mediators and neurotransmitters between the two groups. After 1 week of treatment, serum nerve injury indexes H-FABP, NT-proBNP, NSE and S100B levels of mild hypothermia group were lower than those of routine group;inflammatory mediators sICAM-1, IL-8, IL-13 and IL-18 levels were lower than those of routine group;neurotransmitter Glu level was lower than that of routine group whereas GABA level was higher than that of routine group. Conclusion: mild hypothermia + intravenous thrombolysis therapy can effectively reduce the nerve injury and systemic inflammatory response, and optimize the neurotransmitter distribution in patients with acute cerebral infarction.

Effects of mild hypothermia combined EPO therapy on cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy

Objective:To explore the effects of mild hypothermia combined EPO therapy on cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy. Methods: A total of 72 children with HIE who were diagnosed and treated in the hospital between December 2015 and June 2017 were chosen as the study subjects and divided into control group (n=36) and EPO group (n=36) by random number table method. Control group received mild hypothermia therapy on the basis of conventional therapy, and EPO group received EPO therapy on the basis of the therapy for control group. The differences in serum levels of cerebral injury indexes, myocardial injury indexes and oxidative stress indexes were compared between the two groups before and after treatment.Results: The differences in serum levels of cerebral injury indexes, myocardial injury indexes and oxidative stress indexes were not statistically significant between the two groups before treatment. After the treatment ended, serum cerebral injury indexes VILIP-1, NPY and NSE levels of EPO group were lower than those of control group whereas IGF-1 level was higher than that of control group;myocardial injury indexes CT-1, Myo and cTnⅠ levels were lower than those of control group;oxidative stress indexes GSH-Px and SOD levels were higher than those of control group whereas AOPP and ROS levels were lower than those of control group.Conclusion: Mild hypothermia combined with EPO therapy can improve the cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy.

Effects of mild hypothermia irrigation fluid on nerve function and oxidative stress during intracranial hematoma irrigation

Objective: To study the effects of mild hypothermia irrigation fluid on nerve function and oxidative stress during intracranial hematoma irrigation. Methods: The patients with hypertensive cerebral hemorrhage who received hematoma aspiration in our hospital between August 2014 and November 2017 were chosen and randomly divided into the observation group who received mild hypothermia irrigation fluid and the control group who received room temperature irrigation fluid. Before treatment and 72 h after treatment, the contents of nerve injury markers, cytokines and oxidative stress mediators were measured after peripheral blood extraction and serum separation. Results: Compared with those of control group, serum neuron-specific enolase (NSE), visinin-like protein-1 (VILIP-1), glial fibrillary acidic protein (GFAP), neuropeptide Y (NPY), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), high mobility group protein B1 (HMGB1), macrophage migration inhibitory factor (MIF), interleukin-1β (IL-1β), interleukin-10 (IL-10), malondialdehyde (MDA), 8-OHdG and nitric oxide (NO) contents of observation group were significantly lower whereas serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and total antioxidant capacity (TAOC) contents were significantly higher after treatment (P<0.05). Conclusion: The application of mild hypothermia irrigation fluid during intracranial hematoma irrigation can alleviate the nerve function injury, improve the neurotrophic status and inhibit the oxidative stress response.