Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury

Transplantation of umbilical cord-derived mesenchymal stem cells（UC-MSCs） for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen（HBO） treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized fluid（2.5–3.0 atm impact force）. The injured rats were then administered UC-MSC transplantation via the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function significantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and significantly promotes recovery of neurological functions.

Influence of moderate hypothermia on cerebral oxygenation in pigs with intracranial hypertension

BACKGROUND： Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVE： To observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGN： A randomized controlled trial. SETTING： Department of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALS： Twenty healthy little pigs, either male or female, weighing 4.5-5.5 kg, were used. Neurotrend-typed multiparameter monitoring system （Diametrics Company, British）; CMA/100 micro-injection pump （Carnegie Company, Sweden）. METHODS： The experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups： the normothermia group （control group, n =10） and moderate hypothermia group （n =10）. ① Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure （MEP）, and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide （PaCO2）, arterial partial pressure of carbon dioxide （PaCO2）, HCO3-]. ② Rectal temperature was monitored with mercurial thermometer. ③ Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. ④ Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure （CPP, CPP=MAP（ICP）, brain tissue partial oxygen pressure （PO2）, partial pressure of carbon dioxide （PCO2）, HCO3- and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 ℃ using ice bags, and the body temperature was maintained at 33-35 ℃ for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES： ① MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; ② Results of blood gases analysis in the moderate hypothermia group. RESULTS： All the 20 pigs were involved in the analysis of results. ① MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation： In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [（3.31±1.19）, （5.33±0.95） kPa, P 〈 0.05], CCP was higher, brain tissue PCO2 [（12.03±1.73）, （10.59±2.01） kPa, P 〈 0.05], and brain tissue pH value was higher [（7.03± 1.63）, （9.40±1.30） kPa, P 〈 0.05], whereas the brain temperature was decreased as compared with that before cooling [（34.9±0.3）, （37.2±0.2） ℃, P 〈 0.05]. ② Results of blood gases analysis in the moderate hypothermia group： There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group （P 〉 0.05） CONCLUSION： Moderate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.

HYPERBARIC HYPEROXIA AND THE BRAIN IN VIVO:THE BALANCE BETWEEN THERAPY AND TOXICITY

Hyperbaric oxygenation(HBO)treatment protocols utilize low pressures up to 3ATA.Higher pressures may induce side effects such as convulsions due to brain toxicity.The optimal HBO pressure allowing for maximal therapy and minimal toxicity is under controversy.However,it can be evaluated by monitoring oxygen delivery,saturation,and consumption.In this study,the monitoring system fixed on the rats’brain cortex included a time-sharing fluorometer-reflectometer for monitoring mitochondrial NADH and hemoglobin oxygenation(HbO_(2))combined with Laser Doppler Flowmetry(LDF)for blood-flow monitoring.Rats were located in a hyperbaric chamber and exposed to different pressures.The HBO pressure caused an increase in HbO_(2)and a decrease in NADH in proportion to the increase in hyperbaric pressure,up to a nearly maximum effect at 2.5ATA.At 6ATA,15 minutes before convulsions started,blood volume and NADH started to increase,while tissue O_(2)supply by hemoglobin remained stable.Oxygen pool includes oxygen dissolved in the plasma and also bounded to hemoglobin.Above 2.5ATA,hemoglobin is fully saturated and the oxygen pool nourishment derives only from the oxygen dissolved in the plasma,exceeding the physiological ability for autoregulation;hence,homeostasis is disturbed and convulsions appear.This information is vital because pressures around 2.5ATA–3ATA are standard clinically applied pressures used to treat most of the pathophysiological problems considering the potential benefit which must be balanced against the potential toxicity.This study enables,for the first time,to evaluate the oxygenation level of hemoglobin in the microcirculation.Furthermore,our study showed that additional oxygen pressure(above 2.5ATA)caused brain oxygen toxicity within a short variable period of time after the pressure elevation.

Signals Analysis and Clinical Validation of Blood and Oxygen Data in Human Brain

With a self-made near-infrared analytical instrument to blood and oxygen parameters in human brain, 80 cases in which 20 are healthy persons and 30 are anaesthetised cases and others are patients with heart function lack is taken to examine, and the data of blood and oxygen in brain tissue were collected and analyzed by the method of power spectrum and correlation function. The results indicate that: (1) The average brain oxygen saturation of healthy persons and anaesthetised cases is about 80%, in accord with normal parameter of physiology. Contrastively, the average brain oxygen saturation of patients with heart function lack is 72.8%, which is obviously less than that of healthy persons and anaesthetised cases. The probability of medical statistics is less than 0.01. (2) The shapes of wave of brain blood and oxygen for the healthy person and the anaesthetised case reveal small periodical fluctuations with stable shape and base line, and the trend of increase or decrease of blood and oxygen parameters in brain tissue is synchronous and a phase reversal, but for the patient with heart function lack in a brain oxygen lack state, the shapes of wave are irregular. This is a hint that near infrared light passing through tissue can reflect the intuitionistic change of brain blood and oxygen parameters.(3) The power spectra of brain blood and oxygen for the healthy person and the anaesthetised case has a clear main peak, narrow bandwidth and perfect superposition each other, but the power spectra for the patient with heart function lack in a brain oxygen lack state is on the contrary.(4) The average cross correlation coefficient of brain blood and oxygen for healthy persons and anaesthetised cases is -0.9825±0.1027 close to -1. But the average cross correlation coefficient for patients with heart function lack in a brain oxygen lack state is merely -0.8923±0.1035 which is obviously greater than -1 and the probability of medical statistics is less than 0.01. The clinic experiments have proved that the shapes of waves, the power spectrum and cross correlation coefficient of brain blood and oxygen are useful to analyze the physiological status and changes of blood and oxygen in human brain.

Effects of hyperbaric oxygen treatment on GCS after traumatic brain injury in patients

Objective To evaluate the effects of hyperbaric oxygen therapy (HBOT) on Glasgow Coma Scale (GCC) after traumatic brain injury (TBI) in patients. Methods One hundred and thirty-eight patients with traumatic brain injury were treated by routine therapy combined with HBOT and 29 patients by routine therapy.

Hyperbaric oxygen preconditioning improves postoperative cognitive dysfunction by reducing oxidant stress and inflammation

Postoperative cognitive dysfunction is a crucial public health issue that has been increasingly studied in efforts to reduce symptoms or prevent its occurrence. However, effective advances remain lacking. Hyperbaric oxygen preconditioning has proved to protect vital organs, such as the heart, liver, and brain. Recently, it has been introduced and widely studied in the prevention of postoperative cognitive dysfunction, with promising results. However, the neuroprotective mechanisms underlying this phenomenon remain controversial. This review summarizes and highlights the definition and application of hyperbaric oxygen preconditioning, the perniciousness and pathogenetic mechanism underlying postoperative cognitive dysfunction, and the effects that hyperbaric oxygen preconditioning has on postoperative cognitive dysfunction. Finally, we conclude that hyperbaric oxygen preconditioning is an effective and feasible method to prevent, alleviate, and improve postoperative cognitive dysfunction, and that its mechanism of action is very complex, involving the stimulation of endogenous antioxidant and anti-inflammation defense systems.

Observation on effect of meridian stimulation on blood oxygenation level of brain by applying Near Infra Red Spectrum(NIRS)

Objective To observe the effect of stimulating Yinttang （印堂 EX-HN 3） and Baihui（百会 GV 20） with electroacupuncture （EA） on blood oxygenation level of brain and explore the feasibility of measuring the therapeutic effect of acupuncture by applying near infra red spectrum （NIRS）. Methods Ten participants semi-randomly selected from 158 adults （random test sequence） were stimulated with EA at the acupoints of EX-HN 3 and GV 20. Verbal fluency task was conducted before and after acupuncture, and changes in blood oxygenation level of cerebral cortex were tested by applying NIRS. Quantitative data were processed with JMP 10.0.2 software, and changes in waveforms of blood oxygenation level of brain before and after treatment were compared by applying NIRS. Results ① The mean of reacting dose （integral value） of blood oxygenation level of cerebral cortex of the 158 adults in the verbal fluency task was 10.6 ± 1.1, and the mean of the whole reacting dose of blood oxygenation level of cerebral cortex at 1/2 period of time during the test （centroids value） was 46.8 ± 1.6. ② In the EA group, the mean of integral value and centroids value of 10 adults were 8.4 ± 5.1 and 54.7± 12.2 before EA while 9.8±3.5 and 41.2±6.7 after EA. The integral value and centroids value of the EA group were closer to the mean of all the subjects. Conclusion It was found by NIRS that the blood oxygenation level of cerebral cortex could be regulated in bi- directional way by stimulating EX-HN 3 and GV 20 with EA, and a further research on whether it directly related to EA is to be made.

Clinical, brain electric earth map, endothelin and transcranial ultrasonic Doppler findings after hyperbaric oxygen treatment for severe brain injury

目的 探讨高压氧治疗重型颅脑损伤的疗效及机制。方法 重型颅脑损伤患者 35例为治疗组 ,2 0例为对照组 ,观察高压氧治疗前后临床 (GCS)、脑电地形图 (BEAM)、血内皮素 (ET)、经颅多普勒超声 (TCD)及预后 (GOS)的变化。结果 治疗组患者经高压氧治疗后临床 (GCS)、脑电地形图及预后均明显改善 ,与对照组相比有统计学意义。高压氧治疗 1个疗程后 ,治疗组血内皮素由 91 2 4± 12 18ng/L下降到 6 8 88± 14 37ng/L(P <0 0 1) ;经颅多普勒超声示大脑中动脉Vm也由 6 4 2± 4 8cm/s下降到 51 6± 4 2cm/s(P <0 0 1) ;同时 ,大脑中动脉VsPI也明显下降。统计学有显著性意义 (P <0 0 1)。结论 高压氧治疗能够明显改善重型颅脑损伤患者的临床、脑电地形图及预后 ,并且通过降低急性期血内皮素、改善大脑中动脉血流速度及血管阻力来改善重型颅脑损伤后脑血管痉挛及脑缺血缺氧。同时 ,降低颅内压是高压氧治疗重度颅脑损伤的重要机制之一。

Low-frequency blood oxygen level-dependent fluctuations in the brain white matter： more than just noise

The spontaneous activity of the blood oxygen level-dependent(BOLD)signal has been demonstrated as a promising way for understanding how the brain intrinsically organized.However,most of these studies focused solely on the spontaneous activity in gray matter(GM)and not on white matter(WM).This is

Development of 3-actoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an electron paramagnetic resonance imaging reagent for in vivo mapping brain oxygen distribution and infarction in ischemic brain

Measurement of oxygen concentration and distribution in brain is essential to understanding the pathophysiology of stroke. Although brain oxygen level is critical for brain tissue survival,