Brain protective effect of dexmedetomidine vs propofol for sedation during prolonged mechanical ventilation in non-brain injured patients

BACKGROUND Dexmedetomidine and propofol are two sedatives used for long-term sedation.It remains unclear whether dexmedetomidine provides superior cerebral protection for patients undergoing long-term mechanical ventilation.AIM To compare the neuroprotective effects of dexmedetomidine and propofol for sedation during prolonged mechanical ventilation in patients without brain injury.METHODS Patients who underwent mechanical ventilation for>72 h were randomly assigned to receive sedation with dexmedetomidine or propofol.The Richmond Agitation and Sedation Scale(RASS)was used to evaluate sedation effects,with a target range of-3 to 0.The primary outcomes were serum levels of S100-βand neuron-specific enolase(NSE)every 24 h.The secondary outcomes were remifentanil dosage,the proportion of patients requiring rescue sedation,and the time and frequency of RASS scores within the target range.RESULTS A total of 52 and 63 patients were allocated to the dexmedetomidine group and propofol group,respectively.Baseline data were comparable between groups.No significant differences were identified between groups within the median duration of study drug infusion[52.0(IQR:36.0-73.5)h vs 53.0(IQR:37.0-72.0)h,P=0.958],the median dose of remifentanil[4.5(IQR:4.0-5.0)μg/kg/h vs 4.6(IQR:4.0-5.0)μg/kg/h,P=0.395],the median percentage of time in the target RASS range without rescue sedation[85.6%(IQR:65.8%-96.6%)vs 86.7%(IQR:72.3%-95.3),P=0.592],and the median frequency within the target RASS range without rescue sedation[72.2%(60.8%-91.7%)vs 73.3%(60.0%-100.0%),P=0.880].The proportion of patients in the dexmedetomidine group who required rescue sedation was higher than in the propofol group with statistical significance(69.2%vs 50.8%,P=0.045).Serum S100-βand NSE levels in the propofol group were higher than in the dexmedetomidine group with statistical significance during the first six and five days of mechanical ventilation,respectively(all P<0.05).CONCLUSION Dexmedetomidine demonstrated stronger protective effects on the brain compared to propofol for long-term mechanical ventilation in patients without brain injury.

Phycocyanin for protecting brain ischemia-reperfusion injury and its effect on the expression of Caspase-3 mRNA

BACKGROUND ; Phycecyanin can anti-oxidize and clear free radial. Whether its protective effect on brain is related to Caspase-3, the promoter and operator of apoptosis, is highly concerned. OBJECTIVE： To observe phycocyanin for protecting nerve function and reducing the size of cerebral infarction of rats with brain ischemia-reperfusion and its effect on the expression of Cespese-3 mRNA. DESIGN ： A randomized controlled experiment. SETTING ： Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University MATERIALS： Totally 84 adult healthy female Wistar rats, weighing 210 to 250 g, of clean grade, were provided by the Animal Experimental Center of Shandong University. Phycocyanin （Institute of Oceanography of Chinese Academy of Sciences） was used. METHODS： This experiment was carried out in the Key Laboratory for Prevention and Treatment of Brain Diseases during May to December 2005. ① The rats were randomized into sham-operation group （n=4）, control group （n=-40） and phycocyanin-treated group （n=-40）. Middle cerebral artery occlusion/reperfusion （MACO/R） models were created on the rats of control and phycocyanin-treated groups with suture-occluded method by inserting a thread into left side extemal-internal carotid artery. In the sham-operatien group, inserting suture was omitted. After ischemia for 1 hour and reperfusion for 2 hours, suspension of phycocyanin was intragastdcaUy administrated into the rats of the phycocyanin-treated group at 100 mg/kg , and the same volume of normal saline was isochrenously administrated into the rats of control group as the same. ② Six rats were chosen respectively from the control group and phycocyanin-treated group, then neurologic impairment degrees of rats were evaluated according to Bederson＇s grading. ③ Six rats were chosen respectively from the control and phycocyanin-treated groups. The isolated brain tissue was stained with tdphenyltetrazolium chloride, and then the size of cerebral infarction was calculated with HPIAS-1000 image analytical system by calculating the ratio of cerebral infarction size at each layer and contralateral hemisphere size of the same layer. ④ Twenty--eight rats were chosen respectively from the control and phycocyanin-treated groups, Brain tissue was harvested at reperfusion for 6,12,24 hours and for 2,3,7 and 14 days after ischemia for 1 hour, respectively, 4 rats at each time point. Brain tissue of 4 rats of sham-opera- tion group was harvested at the 24^th hour after operation. Brain tissue sections were performed in situ hybridization detection of Cespase-3 mRNA. MAIN OUTCOME MEASURES： Comparison of neurologic impairment degree, cerebral infarction size and the expression of brain tissue Caspase-3 mRNA of rats between two groups RESULTS： Totally 84 rats entered the stage of result analysis. ① Bederson＇s scores at ischemia and reperfusion for 24 and 48 hours were significantly lower in the phycocyanin-treated group than in the control group（P 〈 0.05）. ② After brain ischemia and reperfusion, the infarction area was the largest in the 3^rc layer in both control and phycocyanin-treated group, which was（25.23±0,47）% and（23.09±120） %, respectively, and the size of infarction area in the 2^nd layer to the 5^th layer was significantly smaller in the phycocyanin-treated group than in the control group （P 〈 0.05）. ③Positive cell counts of brain tissue Caspase-3 mRNA： The number of positive cells of Caspase-3 mRNA of control group was increased from cerebral ischemia and reperfusion 6 hours, reached the peak at ischemia and reperfusion 24 hours, began to decrease 2 days later and positive cells of Caspese-3 mRNA were still expressed on the 14^th day after reperfusion. At ischemia and reperfusion 6,12 and 24 hours as well as 2,3,7 and 14 days, positive cell counts of Caspase-3 at peripheral ischemic area were significantly lower in the phycocyanin-treated greup[（70.67 ±3.65）, （85.06±4.79）, （119.54±5.37）,（74.26±2.19）, （62.06±3.34）, （23.11±1.89）, （10.75±2.63）/visual field] than in the control group [（94.38±8 28）, （108.81 ±16.11）, （140.88±14.47）, （98.13±11.31）, （81.03±9.31）, （31.22±8.86）, （16.06±5.96）Nisual field] （ P 〈 0.05）; and those at central ischemic area were also significantly lower in the phycocyanin-treated group [（33.86±4.01）, （39.51±3.46）, （50.96 ±2.53）, （43.07±4.09）, （36.25 ±3.72）, （9.03±3.87）, （4.91±5.59）/visual field ]than in the control group [（51.35±2.13）, （54.87±3.42）, （61.77±4.94）, （55.69±6.06）, （49.01 ±5.73） ,（12.84±3.37）, （7.32±2.39）/visual field]（P 〈 0.05）. CONCLUSION ： Phycocyanin can obviously improve the neurologic function, reduce the size of brain infarction and down-regulate the expression of Caspase-3 mRNA of rats with ischemia and reperfusion injury, thus protect brain.

Exogenous brain-derived neurotrophic factor attenuates cognitive impairment induced by okadaic acid in a rat model of Alzheimer's disease

Decreased expression of brain-derived neurotrophic factor（BDNF） plays an important role in the pathogenesis of Alzheimer＇s disease, and a typical pathological change in Alzheimer＇s disease is neurofibrillary tangles caused by hyperphosphorylation of tau. An in vivo model of Alzheimer＇s disease was developed by injecting okadaic acid（2 μL） and exogenous BDNF（2 μL） into the hippocampi of adult male Wister rats. Spatial learning and memory abilities were assessed using the Morris water maze. The expression levels of protein phosphatase 2 A（PP2 A）, PP2 Ac-Yp307, p-tau（Thr231）, and p-tau（Ser396/404） were detected by western blot assay. The expression levels of BDNF, TrkB, and synaptophysin mRNA were measured by quantitative real-time polymerase chain reaction. Our results indicated that BDNF expression was suppressed in the hippocampus of OA-treated rats, which resulted in learning and memory deficits. Intra-hippocampal injection of BDNF attenuated this OA-induced cognitive impairment. Finally, our findings indicated an involvement of the PI3 K/GSK-3β/AKT pathway in the mechanism of BDNF in regulating cognitive function. These results indicate that BDNF has beneficial effect on Alzheimer＇s disease, and highlight the potential of BDNF as a drug target for treatment of Alzheimer＇s disease.

Excitatory amino acid changes in the brains of rhesus monkeys following selective cerebral deep hypothermia and blood flow occlusion

Selective cerebral deep hypothermia and blood flow occlusion can enhance brain tolerance to ischemia and hypoxia and reduce cardiopulmonary complications in monkeys. Excitotoxicity induced by the release of a large amount of excitatory amino acids after cerebral ischemia is the major mechanism underlying ischemic brain injury and nerve cell death. In the present study, we used selective cerebral deep hypothermia and blood flow occlusion to block the bilateral common carotid arteries and/or bilateral vertebral arteries in rhesus monkey, followed by reperfusion using Ringer＇s solution at 4~C. Microdialysis and transmission electron microscope results showed that selective cerebral deep hypothermia and blood flow occlusion inhibited the release of glutamic acid into the extracellular fluid in the brain frontal lobe and relieved pathological injury in terms of the ultrastructure of brain tissues after severe cerebral ischemia. These findings indicate that cerebral deep hypothermia and blood flow occlusion can inhibit cytotoxic effects and attenuate ischemic/ hypoxic brain injury through decreasing the release of excitatory amino acids, such as glutamic acid.

Mechanisms and status of research on the protective effects of traditional Chinese medicine against ischemic brain injury

Ischemic brain injury occurs when the metabolic needs of brain tissue cannot be met due to insufficient blood supply to the brain.It is one of the main causes of death and adult disability worldwide.The recurrence rate of ischemic brain injury is high.It places a heavy economic burden on families and society,and seriously affects human health and quality of life.In traditional Chinese medicine,ischemic stroke belongs to the category of“stroke”.The use of traditional Chinese medicine to treat stroke has a long history.After years of experimental research,a large amount of theoretical knowledge and practical experience have been accumulated.Promoting blood circulation and removing blood stasis is the basis of traditional Chinese medicine theory on the treatment of ischemic stroke.Commonly used single Chinese medicines include Chuangxiong(Ligusticum chuanxiong hort),Danggui(Angelica sinensis),Danshen(Salvia miltiorrhiza Bunge),Honghua(Carthamus tinctorius L.),Mudanpi(Moutan Cortex),and Huangqi(Astragali Radix).Buyang Huanwu decoction,Xinglou Chengqi decoction,Taohong Siwu decoction,and other traditional Chinese medicine prescriptions are believed to have a protective effect against brain damage caused by ischemic stroke.With the development of modern medical technology,the mechanism of traditional Chinese medicine treatments for ischemic brain injury has gradually been explored.This article reviews the mechanisms of traditional Chinese medicine’s protection against ischemic brain injury and its current clinical application.

Stimulating mitochondria to protect the brain following traumatic brain injury

Traumatic brain injury （TBI） is an acquired injury to the brain that occurs with sudden trauma that can range from mild （concussive） to severe. TBI is considered a leading cause of death in children and young adults, with the Centers for Disease Control and Prevention estimating that approximately 1.7 million cases of TBI occur in the United States annually （Faul et al., 2010）. Further, since the begin- ning of the global war on terrorism, the Department of Defense has reported over 344,000 U.S. Service Members have been diagnosed with traumatic brain injury from penetrating injuries to mild forms of TBI. TBI, caused by a sudden impact, penetration, or rapid move- ment of the brain, interrupts the normal functioning of the brain. While the intracranial location and severity of injury contribute to the extent of functional deficits.

Protective Effects of Shikonin on Brain Injury Induced by Carbon Ion Beam Irradiation in Mice

Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed protective effect on cerebral ischemic injury. Here we investigated the effects of shikonin on carbon ion beam induced radiation brain injury in mice. Pretreatment with shikonin significantly increased the SOD and CAT activities and the ratio of GSH/GSSG in mouse brain tissues compared with irradiated group （P〈0.01）, while obviously reduced the MDA and PCO contents and the RO$ levels derived from of the brain mitochondria.

Protection of 3'-methoxy-puerarin against focal brain ischemia and its association with c-fos expression

The present study established a rat model of focal brain ischemia by occlusion of the middle cerebral artery covered with FeCl3, and investigated the protective effect of 3＇-methoxy-puerarin. Hippocampal and cortical c-fos gene expression was determined using in situ hybridization. Results showed that 3＇-methoxy-puerarin reduced neurological deficit scores, cerebral infarcted zone and water content of brain tissues, dramatically increased the activity of catalase and glutathione peroxidase in the ischemia zone of the hippocampus, increased the activity of catalase in the cortex, decreased lipid peroxide and lactic acid contents in the hippocampus and cerebral cortex, and down-regulated c-fos gene expression in brain ischemic rats. Results demonstrated that 3＇-methoxy-puerarin exhibited cerebroprotective effects against focal brain ischemia, which involved c-fos gene expression.

Brain protection of AC in PTZ-induced epileptic rats

Objective:To investigate the neuroprotective effect and mechanism of Acteoside(AC)on brain injury in epileptic rats.Methods:30 Sprague-Dawlay rats(SPF grade,healthy males,about 200g)were randomly divided into epilepsy group,AC group and blank control group.The epileptic group and the AC group were given 28 days of intraperitoneal injection of pentaerythritazine(PTZ),and the remaining groups were given normal saline injection.The changes of electroencephalogram(EEG),learning and memory ability,pathological changes of brain tissue,superoxide dismutase(SOD)and malondialdehyde(MDA)were observed in all rats.Results:Compared with the epilepsy group,the AC group showed significantly reduced degeneration and necrosis of nerve cells in brain tissue,significantly improved learning and memory ability,and the EEG was dominated by wavelet and slow wave,replacing the typical spike and spike waves.SOD increased and MDA decreased in oxygen radical(P<0.05).Conclusions:Epilepsy are closely related to Oxidative stress.AC can play a protective role in the brain by improving EEG,learning and memory ability,regulating changes in SOD and MDA content,and inhibiting the generation of oxygen free radicals.

Targeting the body to protect the brain:inducing neuroprotection with remotely-applied near infrared light

The incidence of intractable age-related neurodegenerative conditions such as Alzheimer＇s and Parkinson＇s diseases and age-related macular degeneration is projected to increase substantially over the coming decades with the ageing of the global population. While the burden of disease associ- ated with other chronic conditions has decreased in recent times due to improved diagnosis and treatment, current therapies for neurodegenerative diseases still fall short in that they are only effective in treating signs and symptoms - they do little to slow or prevent disease progress. Thus, there is an urgent need for treatments that address disease progression.

Bone morphogenetic protein signaling：a promising target for white matter protection in perinatal brain injury

Prematurely born newborns,as well as those born at term,may suffer from several types of brain injury including hypoxic-ischemic injury,intracranial hemorrhage,both intraventricular and parenchymal,and injury that is the consequence of intrauterine growth restriction（IUGR）.Injury of all types can impact the motor and cognitive abilities of survivors.The mechanisms leading to disability are not completely understood.

Effects of Lead on pH and Temperature-Dependent Substrate-Activation Kinetics of ATPase System and its Protection by Thiol Compounds in Rat Brain

Lead (Pb) inhibited the activities of Na+ -K+ ATPase (IC50= 2.0×10^(-6) M), K + -Para-Nitrophenyl phosphatase (PNPPase) (IC50= 3.5×10^(-6) M) and [3H]-ouabain binding (IC50 = 4.0×10^(-5) M) in rat brain P2 fraction. A variable temperature or pH significantly elevated the inhibition of Na+-K+ ATPase by Pb in buffered acidic, neutral and alkaline pH ranges. Noncompetitive inhibition with respect to activation of Na+ -K+ ATPase by ATP was indicated by a variation in Vmax values with no significant changes in Km values at any temperature studied. In the presence of Pb, for Na+ -K+ ATPase at pH 6.5 and 8.5, Vmax was decreased with an increase in Km values suggesting a mixed type of inhibition. Sulfhydryl agents such as dithiothreitol (DTT) and cvsteine (Cyst), but not glutathione (GSH) offered varied levels of protection against Pb-inhibition of Na + -K+ ATPase at pH 7.5 and 8.5. The present data suggest that inhibition of Na+ -K+ ATPase by Pb is both temperature and pH-dependent. These results also indicate that Pb inhibited Na + -K + ATPase by interfering with phosphorylation of enzyme molecule and dephosphorylation of the enzyme-phosphoryl complex and exerted an effect similar to that of SH-blocking agents.

Clinical application of retrograde cerebral perfusion for brain protection during the surgery of ascending aortic aneurysm:50 cases report

Objective To assess retrospectively the effects of different protective methods on brain in ascending aortic aneurysm surgery. Methods In 65 patients, aneurysm was dissected to the aortic arch or right arch. To protect brain, deep hypotermic circulatory arrest ( DHCA.) combined with retrograde cerebral perfusion ( RCP) June 2003 Vol11 No2 through the superior vena cava ( n = 50) and simple DHCA ( n = 15) were used during the procedure. Blood samples for lactic acid level from the jugular vein were compared in both groups at different plase, and perfusion blood distribution and oxygen content difference between the perfused and returned blood were measured in some RCP patients. Results The DHCA time was 35.9 ± 8 min (10. 0 - 63. 0 min) and DHCA+ RCP time was 45.5 ± 17. 2 min (16. 0 - 81. 0 min)The resuscitationtime was 7.1 ± 1.6 h (4.4 - 9.4H)in DHCA patients and 5.4±2.2h(2.0-9.0 h)in RCP patients. Operation death was 3/15 in the DHCA group and 1/50 in the RCP patients. Central nervous complication

Protective effect of ultrashortwave versus radix salviae miltiorrhizae on brains of rats with cerebral ischemia-reperfusion injury

BACKGROUND： HOW to control the effect of oxygen-derived free radicals on development of cerebral injury and cerebral edema is a key factor for treating cerebral ischemia-reperfusion injury. OBJECTIVE： To observe and compare the protective effects, synergistic action and mechanisms of ultrashortwave （USW） and radix salviae miltiorrhizae （RSM） on the focal cerebral ischemia-reperfusion injuries in rats. DESIGN： Randomized controlled animal study SEI-FING： Department of Rehabilitation Medicine, First Hospital affiliated to China Medical University MATERIALS： A total of 160 healthy Wistar rats of both genders and aged 18-20 weeks weighing 250-300 g of clean grade were selected in this study. 5 mL/ampoule RSM injection fluid was produced by the First Pharmaceutical Corporation of Shanghai （batch number： 011019, 0.01 mug）. The USW therapeutic device was produced by Shanghai Electronic Device Factory with the frequency of 40.68 MHz and the maximal export power of 40 W. The first channel of power after modulation was 11 W. METHODS： The experiment was carried out in the Rehabilitation Medicine Department of the First Hospital affiliated to China Medical University from May 2002 to January 2003. Focal ischemia-reperfusion model was established in rats by reversible right middle cerebral artery occlusion with filament. Right cerebral ischemia was for 2 hours and then with 24 hours reperfusion. The scores of neurological deficits were evaluated by 0 to 4 scales. After surgery, 64 successful rats models were divided into four groups according to digital table： control group, USW group, RSM group and RSM ＋ USW group with 16 cases in each group. Rats in control group were intraperitoneally injected with the same volume of saline （0.1 mL/g）; rats in USW group were given small dosage of USW on head for 10 minutes at 6 hours after reperfusion; rats in RSM group were intraperitoneally injected with 0.01 mL/g RSM solution at 30 minutes before reperfusion; rats in RSM ＋ USW group were intraperitoneally injected with 0.01 mL/g RSM parenteral solution at 30 minutes before reperfusion and given small dosage of USW on head for 10 minutes once at 6 hours after reperfusion; sixteen rats in sham operation group did not receive any treatment. All 80 rats were taken brains at 24 hours after reperfusion to measure wet and dry weights to calculate water content： Cerebral water content （%） = （1-dry/wet weight） × 100%. Superoxide dismutase （SOD） activity was measured by hydroxylamine method and malondialdehyde （MDA） content was measured by TBA photometric method. MAIN OUTCOME MEASURES ： Cerebral water content, SOD activity and MDA content RESULTS： All 160 rats except 80 failing in modeling were involved in the final analysis. （① The cerebral water content of left hemisphere made no significant difference （P 〉 0.05）. The cerebral water content of right hemisphere in the control group and the three treatment groups was obviously higher than that of the sham operation group [（81.26±0.77）%, （79.74±0.68）%, （79.76±0.81）%, （79.61±0.79）%, （77.43±0.61）%, P 〈 0.05]. The cerebral water content of right hemisphere in the three treatment groups was obviously lower than that of the control group （P〈 0.05）. There was no significant difference among the three treatment groups （P 〉 0.05）. ② Compared with the control group, SOD activity （right） of the control group decreased obviously （P 〈 0.05）, while MDA content increased obviously （P 〈 0.05）. SOD activity in the three therapeutic groups increased obviously, while MDA content decreased obviously （P 〈 0.05）; there was no significant difference among the three treatment groups （P 〉 0.05）. CONCLUSION： ① USW and RSM therapy have neuroprotective effects against focal cerebral ischemia-reperfusion injuries by means of decreasing cerebral water content and MDA and increasing the activity of SOD. ② Synergistic action was not observed between these two therapeutic methods.

Acupuncture promotes functional recovery after cerebral hemorrhage by upregulating neurotrophic factor expression

Acupuncture is widely used in the treatment of cerebral hemorrhage,and it improves outcomes in experimental animal models and patients.However,the mechanisms underlying the effectiveness of acupuncture treatment for cerebral hemorrhage are still unclear.In this study,a model of intracerebral hemorrhage was produced by injecting 50μL autologous blood into the caudate nucleus in Wistar rats.Acupuncture at Baihui(DU20)and Qubin(GB7)acupoints was performed at a depth of 1.0 inch,12 hours after blood injection,once every 24 hours.The needle was rotated at 200 r/min for 5 minutes,For each 30-minute session,needling at 200 r/min was performed for three sessions,each lasting 5 minutes.For the positive control group,at 6 hours,and 1,2,3 and 7 days after induction of hemorrhage,the rats were intraperitoneally injected with 1 mL aniracetam(0.75 mg/mL),three times a day.The Bederson behavioral test was used to assess palsy in the contralateral limbs.Western blot assay was used to examine the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia.Immunohistochemistry was performed to count the number of Nestin-and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia.Acupuncture effectively reduced hemorrhage and brain edema,elevated the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia,and increased the number of Nestin-and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia.Together,these findings suggest that acupuncture promotes functional recovery after cerebral hemorrhage by increasing the expression of neurotrophic factors.The study was approved by the Committee for Experimental Animals of Heilongjiang Medical Laboratory Animal Center(approval No.2017061001)on June 10,2017.

Energy conversion in woodpecker on successive peckings and its role on anti-shock protection of brain

To investigate the mechanism of brain protection of woodpecker,we built a finite element model of a whole woodpecker using computed topography scanning technique and geometry modeling.Dynamic analyses reveal:(i)99.7%of the impact energy is converted into strain energy in the bulk of body and 0.3%is converted into strain energy in the head after three successive peckings,indicating the majority of the impact energy is stored in the bulk of body;(ii)the strain energy in brain is mainly converted into the dissipated energy,alleviating the mechanical injury to brain;(iii)the deformation and the effective energy dissipation of the beaks facilitate the decrease of the stress and impact energy transferred to the brain;(iv)the skull and dura mater not only provide the physical protection for the brain,but also diminish the strain energy in the brain by energy dissipation;(v)the binding of skull with the hyoid bone enhances the anti-shock ability of head.The whole body of the woodpecker gets involved in the energy conversion and forms an efficient anti-shock protection system for brain.

A NOVEL DIRECT ACTIVATOR OF TFEB PROMOTES AUTOPHAGY AND LYSOSOME BIOGENESIS AND PROTECTS NEURONS IN THE BRAIN

Autophagy dysfunction is a common feature in neurodegenerative disorders caused by the accumulation of toxic,aggregate-prone proteins.Increasing evidence have demonstrated that genetic or pharmacological activation of transcription factor EB(TFEB),a master regulator of autophagy and lysosomal biogenesis,ameliorates neurotoxicity and rescues neurodegenerative phenotypes in several animal models of neurodegenerative diseases.