BACKGROUND: The therapeutic effect of mild hypothermia in the treatment of severe brain injury has been recognized in spite of the poor understanding of its mechanism. Until now, no reports have been available to describe the changes in cerebral oxygen metabolism following serious brain and during mild hypothermia treatment.OBJETCIVE: To observe the patterns of cerebral oxygen metabolism changes during mild hypothermia treatment for severe brain injury, and explore the mechanism of the therapeutic effect of mild hypothermia.DESIGN: A clinical observation of factorial design.SETTING: Mild Hypothermia Treatment Center of Tianjin Huanhu Hospital.PARTICIPANTS: From August 1998 to January 2000, 13 patients with severe brain injury were treated in Mild Hypothermia Treatment Center of Tianjin Huanhu Hospital, including 11 males and 2 females aged 18-65 years. Diagnosis of brain contusion and laceration with subdural hematoma was established in 6 cases, epidural hematoma in 1 case, subarachnoid hemorrhage in 4 cases and diffuse axonal injury in 2 cases. Of these cases 7 were treated with conservative therapy, and 6 with internal/external decompression after surgical hematoma removal.METHODS: A blanket for controlling the body temperature was applied to induce whole-body hypothermia in the patients in the mild hypothermia treatment room with continuous intravenous infusion of chlorpromazine (100 mg), promethazine (100 mg) and atracurium besilate (400 mg) administered in 500 mL normal saline. Neurotrend-7TM multi-parameter monitoring system was used to for monitoring the dynamic changes of cerebral PO2,PCO2, pH and brain temperature to evaluate their changes after treatment.The correlation between cerebral oxygen metabolism and the scores of Glasgow Coma Scale was analyzed.MAIN OUTCOME MEASURES: Dynamic changes of cerebral PO2,PCO2, pH and brain temperature.RESULTS: All the 13 patients entered the final analysis. Eighteen hours after hypothermia, the PO2 [(2.23±1.29) kPa] was obviously increased in comparison with that before hypothermia [(1.29±0.57) kPa, t=2.449, P ＜ 0.05], and PCO2 exhibited significant decrease at hypothermia 6 hours to (7.32±0.92) kPa from the pre-treatment level of (7.75±1.07) kPa (t=2.446, P ＜ 0.05). Significant elevation of pH and descension of intracranial pressure occurred upon the achievement of hypothermia [7.06±0.15 vs 6.83±0.20 for pH, t=5.164, P ＜ 0.05;(2.03±1.01) vs (2.57±0.93) kPa for intracranial pressure, t=2.948, P ＜ 0.05].Six hours after hypothermia, the cerebral perfusion pressure was obviously higher than that before hypothermia [(9.40±1.80) vs (7.80±1.59) kPa, t=2.365,P ＜ 0.05]. PCO2 was found inversely correlated with Glasgow Outcome Scale (GOS) scores at 24 hours of hypothermia (r=-0.699, P ＜ 0.05). The variations of cerebral oxygen metabolism indices before and after mild hypothermia were positively correlated with GOS scores.CONCLUSION: Dynamic monitoring of cerebral oxygen metabolism is safe and effective, and may help in early detection of cerebral hypoxia and acidosis following severe brain injury. Mild hypothermia treatment can effectively alleviate hypoxia and acidosis following severe brain injury to improve the prognosis of the patients.

There are a lot of reports about the neuroprotection of mild hypothermia in the acute phase brain injury of aneurysmal subarachnoid hemorrhage. There are many mechanisms of brain damage involving in the development of brain damage in the acute phase of aneurysmal subarachnoid hemorrhage. Mild hypothermia can protect against various brain damages in the early stage of cerebral infarction. It may play a role in brain protection when it is used in the acute phase of aneurysmal subarachnoid hemorrhage.

Objective To study the influence of mild hypothermia on blood glucose and blood lactate and intracranial pressure (ICP) of the patients with anterior circulation brain infarction (massive hemispheric infarction) and evaluate its clinical effects.Methods All 30 patients with massive hemispheric infarction within the first 24 hours from stroke onset were randomly divided into the control group and the hypothermia group (15 patients respectively). To the latter group, mild hypothermia (32~34℃)was initiated and ICP values were measured in the same time. Rewarming was begun after hypothermic therapy lasted for 20~49(32?9)hours. In both groups, the blood glucose and blood lactate were measured at the time of admission, the second day and the fourth day. According to Neurological Deficit Scale score, the prognosis was evaluated at the time of admission and 4 weeks later.Results In hypothermia group, the initial ICP was (14.2?4.2) mm Hg, which was significantly reduced under hypothermia to (11.3?2.8) mm Hg(P

Objective To study the expressions of erythmpoietin(EPO)and its receptors(EPOR)in the injured brain tissue ofthe rats with traumatic brain injury(TBI).Methods A total of78 SD rats were randomly divided into three groups including control group(six rats),sham group(36rats) and fluid percussion injury group(36 rats).The rats were sacrificed at 6,24 hours,3,5,7 and 14days after TBI in the sham group and the fluid percussion injury group(six rats at each time point).Then,the injured brain tissues were removed for observation of the mRNA and protein expressions of EPO and EPOR by meaDiB of real-time PCR and Western blot. Results The expression of EPO was increased at 24 hours and reached the peak at day 3 after TBI.The hish expression level of EPO could maintain for two days or so.began to decrease at day 7 and recovered to normal at day 14 after Till.While the expression of EPOR reached the peak at 24 hours after TBI and maintained hish level at day14. Conclusions The expressions of EPO and EPOR show increase within 24 hours after TBI.In fact,the expressions of both factors are not in consistency,with more transient expression of EPO.

OBJECTIVETo study the changes of partial pressure of oxygen in brain tissue (P(bt)O(2)) and brain temperature (BT) in patient s in acute phase of severe head injury, and to study the effect of mild hypothermia on P(bt)O(2) and BT.

METHODSThe P(bt)O(2) and the BT of 18 patients with severe head injury were monitored, and the patients were treated with mild hypothermia within 20 hours after injury. The rectal temperature (RT) of the patients was kept on 31.5-34.9 degrees C for 1-7 days (57.7 hours+/-28.4 hours averagely), simultaneously, the indexes of P(bt)O(2) and BT were monitored for 1-5 days (with an average of 54.8 hours+/-27.0 hours). According to Glasgow Outcome Scale (GOS), the prognosis of the patients was evaluated at 6 months after injury.

RESULTSWithin 24 hours after severe head injury, the P(bt)O(2) was significantly lower (9.6 mm Hg+/-6.8 mm Hg, 1 mm Hg=0.133 kPa) than the normal value (16-40 mm Hg). After treatment of mild hypothermia, the mean P(bt)O(2) increased to 28.7 mm Hg+/-8.8 mm Hg during the first 24 hours, and the P(bt)O(2) was still maintained within the range of normal value at 3 days after injury. The BT was higher than the RT in the patients in acute phase of severe head injury, and the difference between the BT and the RT significantly increased after treatment of mild hypothermia. Hyperventilation (the partial pressure of carbon dioxide in artery (P(a)CO(2)) approximately 25 mm Hg) decreased the high intracranial pressure (ICP) and significantly decreased the P(bt)O(2).

CONCLUSIONSThis study demonstrates that P(pt)O(2) and BT monitoring is a safe, reliable and sensitive diagnostic method to follow cerebral oxygenation. It might become an important tool in our treatment regime for patients in the acute phase of severe head injury requiring hypothermia and hyperventilation.

Adult ; Aged ; Blood Gas Monitoring, Transcutaneous ; Body Temperature ; Brain ; metabolism ; Craniocerebral Trauma ; metabolism ; therapy ; Female ; Glasgow Coma Scale ; Humans ; Hypothermia, Induced ; Male ; Middle Aged ; Oxygen ; metabolism ; Treatment Outcome

The extracellular matrix metalloproteinase inducer (EMMPRIN) has been known to play a key regulatory role in pathological angiogenesis. A elevated activation of vascular endothelial growth factor (VEGF) following radiation injury has been shown to mediate blood-brain barrier (BBB) breakdown. However, the roles of EMMPRIN and VEGF in radiation-induced brain injury after gamma knife surgery (GKS) are not clearly understood. In this study, we investigated EMMPRIN changes in a rat model of radiation injury following GKS and examined potential associations between EMMPRIN and VEGF expression. Adult male rats were subjected to cerebral radiation injury by GKS under anesthesia. We found that EMMPRIN and VEGF expression were markedly upregulated in the target area at 8-12 weeks after GKS compared with the control group by western blot, immunohistochemistry, and RT-PCR analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals colocalized with caspase-3 and VEGF-positive cells. Our data also demonstrated that increased EMMPRIN expression was correlated with increased VEGF levels in a temporal manner. This is the first study to show that EMMPRIN and VEGF may play a role in radiation injuries of the central nervous system after GKS.
Animals ; Antigens, CD147/*metabolism ; Brain/blood supply/metabolism/pathology/*radiation effects ; Brain Injuries/metabolism/pathology ; Caspase 3/metabolism ; Gamma Rays/*adverse effects ; Immunohistochemistry ; Male ; Microscopy, Electron, Transmission ; Parietal Lobe/metabolism/pathology/radiation effects ; Radiation Injuries, Experimental/metabolism ; Radiosurgery/adverse effects ; Rats ; Rats, Wistar ; Time Factors ; Vascular Endothelial Growth Factor A/*metabolism