Effect of long-term mild hypothermia or short-term mild hypothermia on outcome of patients with severe traumatic brain injury.

To compare the effect of long-term mild hypothermia versus short-term mild hypothermia on the outcome of 215 severe traumatic brain injured patients with cerebral contusion and intracranial hypertension. At three medical centers, 215 patients aged 18 to 45 years old with an admission Glasgow Coma Scale < or =8 within 4 h after injury were randomly divided into two groups: long-term mild hypothermia group (n = 108) for 5+/-1.3 days mild hypothermia therapy and short-term mild hypothermia group (n = 107) for 2+/-0.6 days mild hypothermia therapy. All patients had intracranial hypertension and frontotemporoparietal contusion with midline shift >1 cm confirmed on computed tomographic scan. Glasgow Outcome Scale at 6-month follow-up, 47 cases had favorable outcome (43.5%), and other 61 cases had unfavorable outcome (56.5%) in the long-term mild hypothermia group. However, only 31 cases had favorable outcome (29.0%), and other 76 cases had unfavorable outcome (71.0%) in the short-term mild hypothermia group (P < 0.05). The intracranial pressure significantly rebounded after rewarming in the short-term mild hypothermia group, but not in the long-term mild hypothermia (P < 0.05). Furthermore, the incidence of stress ulcer, epilepsy, pulmonary infection, intracranial infection did not significantly differ between the two groups (P > 0.05). Compared with short-term mild hypothermia, long-term mild hypothermia significantly improves the outcome of severe traumatic brain injured patients with cerebral contusion and intracranial hypertension without significant complications. Our data suggest that 5 days of long-term cooling is more efficacious than 2 days of short-term cooling when mild hypothermia is used to control refractory intracranial hypertension in patients with severe traumatic brain injury.     

Assessment of prognostic factors in severe traumatic brain injury patients treated by mild therapeutic cerebral hypothermia therapy

This study analyzed the predictable factors of outcome such as neuro-parameters and systemic complications to elucidate the indications for therapeutic hypothermia. In our institute, 35 patients with severe head injury (Glasgow Coma Scale 3-7) were treated with mild hypothermia therapy (33 degrees-35 degrees C). Twenty-two of these 35 patients underwent complete neuromonitoring and outcome assessments by Glasgow Outcome Scale (GOS) at three months after injury. GOS of hypothermia group was significantly better than another patient group which was treated without mild hypothermia therapy. The hypothermia group was divided into two groups: good outcome (GOOD) (good recovery or moderate disability; n = 9, 40.9%) and poor outcome (POOR) (severe disability, vegetative state, or death; n = 13, 59.1%). The mean age (mean 30.2 years, range 9-46) was significantly lower in GOOD than in POOR (mean 45.2 years, range 17-62). Patients aged over 50 years had poor outcome. CPP was significantly higher in GOOD during hypothermia. All patients with thrombocytopenia had poor outcome. Hypothermia therapy can improve outcome in patients with traumatic brain injury who are younger than 50 years old, without severe brain damage, and if improvement of cerebral perfusion is expected. Systemic complications must be prevented as far as possible by combination with other therapies.     

Assessment of prognostic factors in severe traumatic brain injury patients treated by mild therapeutic cerebral hypothermia therapy

Abstract

This study analyzed the predictable factors of outcome such as neuro-parameters and systemic complications to elucidate the indications for therapeutic hypothermia. In our institute, 35 patients with severe head injury (Glasgow Coma Scale 3-7) were treated with mild hypothermia therapy (33° - 35°C). Twenty-two of these 35 patients underwent complete neuromonitoring and outcome assessments by Glasgow Outcome Scale (GOS) at three months after injury. GOS of hypothermia group was significantly better than another patient group which was treated without mild hypothermia therapy. The hypothermia group was divided into two groups: good outcome (GOOD) (good recovery or moderate disability; n = 9, 40.9%) and poor outcome (POOR) (severe disability, vegetative state, or death; n = 13, 59.1%). The mean age (mean 30.2 years, range 9-46) was significantly lower in GOOD than in POOR (mean 45.2 years, range 17-62). Patients aged over 50 years had poor outcome. CPP was significantly higher in GOOD during hypothermia. All patients with thrombocytopenia had poor outcome. Hypothermia therapy can improve outcome in patients with traumatic brain injury who are younger than 50 years old, without severe brain damage, and if improvement of cerebral perfusion is expected. Systemic complications must be prevented as far as possible by combination with other therapies.     

IHAST II and the response of neuroanaesthetists.

Deliberate mild hypothermia was first used in 1955 as an intraoperative technique to ameliorate new neurological deficits following cerebral aneursym clipping, and subsequently was also used following neonatal asphyxia, head trauma and cardiac arrest. The Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST II) randomized control trial was designed to determine the effectiveness of mild hypothermia to decrease neurological deficits following aneurysm surgery. No overall benefit was demonstrated in the hypothermic group versus normothermic group (67% versus 63% good outcome; p=0.32), with a higher rate of bacteraemia in the hypothermic group (5% versus 3%; p=0.05). We undertook a survey of Australasian and Asian neuroanaesthetists to determine whether their thermal management of patients undergoing cerebral aneursym clipping had changed in response to the IHAST II trial results.     

Hypothermia as a neuroprotective agent

Hypothermia has long been employed for therapeutic purposes but its use has been limited because of the potential life-threatening side-effects. In late eighties a neuroprotective effect of bold hypothermia was demonstrated and this implied that the method could be used more safely. It has then been shown in a lot of animal experiments that post-ischaemic mild hypothermia significantly limits damage to the brain caused by cardiac arrest. Similar results have been obtained for local brain ischaemia and for experimental head trauma. Molecular basis for this neuroprotection with mild hypothermia has been found to be complex, involving attenuation of the excitotoxic effects of glutamate and diminishing the synthesis of free radicals. In the last decade some clinical series and multicenter randomised trials have shown that mild hypothermia is safe and effective in global brain ischaemia due to cardiac arrest. Clinical data suggest also its effectiveness in ischaemic stroke though no multicenter randomised study has been published to date. At present there are conflicting results of clinical trials concerning brain injuries. Although some authors have reported up to 38% improvement in the outcome, a recently published multicenter randomised trial has failed to demonstrate any practical benefit of mild hypothermia after acute brain injury. There is however virtually no data in the literature on mild hypothermia in spinal cord injury.     

Safety and therapeutical benefit of hemicraniectomy combined with mild hypothermia in comparison with hemicraniectomy alone in patients with malignant ischemic stroke

INTRODUCTION: Both for hemicraniectomy and for hypothermia, several reports describe a beneficial effect in patients with malignant supratentorial cerebral ischemia. We compared the safety and the clinical outcome in patients with a malignant supratentorial infarction who were treated with hemicraniectomy alone (HA) or received a combination therapy with hemicraniectomy and hypothermia of 35 degrees C (HH), respectively. METHODS: In a prospective and randomized study, 25 consecutive patients were treated after an ischemic infarction of more than two thirds of one hemisphere by HA (n=13 patients) or the HH combination therapy (n=12 patients). Safety parameters were compared between both treatment groups, the clinical outcome was assessed during treatment and after 6 months. RESULTS: Age, cranial CT or MRI findings, initial National institutes of Health Stroke Scale Score (NIHSSS) and level of consciousness were not significantly different between both groups. Hemicraniectomy was performed within 15+/- 6 h after the ischemic event. Hypothermia was induced immediately after surgery. Overall mortality was 12% (2/13 vs. 1/12 in the two groups), but none of these 3 patients died due to treatment-related complications. There were no severe side effects of hypothermia. Duration of need for intensive care or for mechanical ventilation and infectious status did not differ significantly between both groups, but the need for catecholamine application was increased in the HH group. The clinical outcome showed a tendency for a better outcome in the HH compared with the HA group with respect to status after 6 months, as assessed by the NIHSSS (10+/-1 vs. 11+/-3, p<0.08). DISCUSSION: The present study suggests that a combined therapy of mild hypothermia and hemicraniectomy in malignant brain infarction does not imply additional risks by side effects and improves functional outcome as compared with hemicraniectomy alone.     

Combination drug therapy and mild hypothermia: a promising treatment strategy for reversible, focal cerebral ischemia.

BACKGROUND AND PURPOSE: Hypothermia has been suggested to be the most potent therapeutic approach to reduce experimental ischemic brain injury identified to date, and mild hypothermia is increasingly used for neuroprotection during neurovascular surgery. We have recently demonstrated that combined administration of tirilazad mesylate and magnesium provides for an overall enhanced neuroprotective effect. The present study was designed to determine whether the efficacy of mild hypothermia (33 degrees C) can be increased by combination pharmacotherapy with tirilazad and magnesium (MgCl(2)). METHODS: Forty Sprague-Dawley rats were subjected to transient, middle cerebral artery occlusion and were randomly assigned to 1 of 4 treatment arms (n=10 each): (1) normothermia+vehicle, (2) normothermia+tirilazad+MgCl(2), (3) hypothermia+vehicle, or (4) hypothermia+tirilazad+MgCl(2). Cortical blood flow was monitored by a bilateral laser-Doppler flowmeter, and the electroencephalogram was continuously recorded. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed after 7 days. RESULTS: Tirilazad+MgCl(2), hypothermia, and hypothermia+tirilazad+MgCl(2) reduced total infarct volume by 56%, 63%, and 77%, respectively, relative to controls. In animals treated with both hypothermia and combination pharmacotherapy, cortical infarction was almost completely abolished (-99%), and infarct volume in the basal ganglia was significantly reduced by 55%. In addition, this treatment provided for the best electrophysiological recovery and functional outcome. CONCLUSIONS: The neuroprotective efficacy of hypothermia can be increased by pharmacological antagonism of excitatory amino acids and free radicals by using clinically available drugs. This treatment strategy could be of great benefit when applied during temporary artery occlusion in cerebrovascular surgery.     

外伤性慢性硬脑膜下血肿发生机理探讨

目的：探讨慢性硬脑膜下血肿（CSDH）的发生机理，方法：对我科1997年至1999年治疗的17例急性硬脑膜下血肿（ASDH），11例CSDH及9例硬脑膜下积液病人进行观察分析，结果：17例ASDH非手术治疗后无1例发展成为CSDH，9例硬脑膜下积液有2例发展成为CSDH，1例发展为张力性硬脑膜下积液。11例CSDH病人中，在第一次外伤后72h内头部CT示6例硬脑膜下积液，4例脑挫伤，1例无特殊显示，无一例为硬膜下血肿，结论：CSDH的发生可能与硬脑膜下积液有密切关系。     

The use of mild hypothermia for patients with severe vasospasm: a preliminary report.

The purpose of this study was to determine the effect of mild hypothermia on cerebral ischaemia due to severe vasospasm, which was refractory to medical and intravascular treatments and to assess the brain protection of this treatment in patients who underwent delayed aneurysm clipping after presenting with ischaemic neurological deficits. Mild hypothermia (32-34 degrees C of brain temperature) was employed in two groups: (1) Patients (Hunt and Kosnik grades I to II) who showed progressive neurological deficits due to vasospasm and did not respond to conventional therapy (Group 1) and (2) Patients who received delayed aneurysm clipping after presenting with ischaemic neurological deficits due to vasospasm (Group 2). Seven of 8 patients in both Groups showed a favorable outcome with mild hypothermia (good recovery in 5 and moderate disability in two patients). Mild hypothermia is considered to be effective on critical cerebral ischaemia due to vasospasm even after failure to response the conventional therapies and to provide brain protection in delayed aneurysm clipping.     

Therapeutic effect of post-ischemic hypothermia duration on cerebral ischemic injury

OBJECTIVE: To study the efficacy of post-ischemic mild brain hypothermia lasting for different time intervals on cerebral ischemic reperfusion injury. METHOD: Male Sprague-Dawley rats were divided into a sham-operated group, normothermia (37-38 degrees C) ischemia group and mild hypothermia (31-32 degrees C) group. The last group was subdivided into four groups: 30 minute hypothermia plus 210 minute normothermia, 60 minute hypothermia plus 180 minute nomothermia,120 minute hypothermia plus 120 minute normothermia, and 240 minute hypothermia (n=8). Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model. Brain tissue was collected following a 20 minute cerebral ischemia and 240 minute reperfusion, and was used to measure the levels of glutamate (Glu), aspartate (Asp), glycine (Gly), gamma-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin(5-HT) and hydroxyindoleacetic acid (5-HIAA), nitrite (NO(2)), endothelin-1 (ET(1)), tumor necrosis factor alpha(TNFalpha) and interleukin-1beta (IL-1beta). Serum was collected to measure the levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK) and its brain band isoenzyme (CK-BB). RESULTS: Hypothermia lasting for 60-240 minutes delayed the decrease in these amino acids, postponed the decrease in DA, NE and 5-HT and increase in hydroxyindoleacetic acid (5-HIAA), and decreased the levels of IL-1beta, TNFalpha, ET(1) and NO(2) in brain tissue. Hypothermia also decreased the levels of LDH, AST, CK and CK-BB in serum as compared to normothermia group (p<0.05 or p<0.01). Hypothermia lasting for 30 minutes delayed the decreases in these amino acids and 5-HT and increase in 5-HIAA in brain tissue (p<0.05), but failed to influence the levels of IL-1beta, TNFalpha, ET(1) and NO(2) in brain tissue and the amounts of LDH, AST, CK and CK-BB in serum as compared to normothermia ischemia group (p>0.05). CONCLUSIONS: Post-ischemic mild brain hypothermia can significantly suppress the excessive release of amino acids, monoamine neurotransmitters and inflammation response in ischemic tissue. It can also stabilize the function of the cell membrane, which is associated with the mechanism of cerebral protection by mild hypothermia. These results suggest that mild hypothermia should be applied immediately after ischemia and last for more than 60 minutes in order to obtain neuroprotective effects.     

急性重型颅脑损伤患者脑组织PO2、PCO2和pH变化的临床研究

目的：探讨急性重型颅脑损伤患伤后脑组织PO2、PCO2和pH（PbrO2、PbrCO2、pHbr)变化规律及其临床意义，观察亚低温对PbrO2、PbrCO2和pHbr的影响。方法：64例重型颅脑损伤患伤后放置PbrO2、PbrCO2和pHbr光纤探头连续监测脑组织PbrO2、PbrCO2和pH变化。结果：伤后3个月的格拉斯哥预后记分（GOS）与PbrO2、PbrCO2和pHbr的变化有明显相关，预后较佳组患（GOS4－5分）的PbrO2、PbrCO2和pH明显优于预后不良组（GOS1－3分）。亚低温对颅脑伤后PbrO2的改善不明显，但能明显降低PbrCO2含量，减轻酸中毒。结论：监测PbrO2、PbrCO2和pHbr变化为研究重型颅脑损伤患伤后脑组织氧代谢和酸碱平衡变化规律、指导临床治疗有重要价值。     

Neuroprotection in ischemic stroke--combination drug therapy and mild hypothermia in a rat model of permanent focal cerebral ischemia

We have recently demonstrated marked neuroprotective efficacy of a combination therapy with magnesium (calcium- and glutamate-antagonist), tirilazad (antioxidant) and mild hypothermia (MTH) in a rat model of transient focal cerebral ischemia. In the present study, we investigated MTH under conditions of permanent focal cerebral ischemia. In part I, 20 Sprague-Dawley rats were subjected to 6 h of permanent, laser-Doppler flowmetry (LDF) controlled middle cerebral artery occlusion (MCAO). Drugs were administered 30 min before and 1 h after MCAO. Hypothermia (33 degrees C) was maintained for 2 h. Infarct size was planimetrically determined after 6 h. In part II, 29 rats were assigned to the same treatment arms and subjected to 7 days of permanent MCAO. Neurological deficits and body weight were assessed daily. Infarct size was determined on day 7. In part I, MTH significantly reduced infarct formation by 52% after 6 h. In part II, high mortality within the first 3 days was observed in both groups. Treated animals showed a significantly better postoperative weight gain on day 7 and neurological recovery on days 6 and 7 compared to controls without significant differences in infarct volume. MTH seems to exert its neuroprotective properties even in a setting of permanent cerebral ischemia. High mortality and absence of infarct reduction after 7 days might be due to model limitations. Neurological recovery, the most important clinical outcome parameter, is significantly improved in 7-day survivors. Significant neuroprotection under conditions of permanent ischemia and former promising results in transient ischemia justify further investigations of MTH.     

Mild hypothermia therapy for patients with severe brain injury

The authors present a group of patients with severe head injuries in which deliberate mild hypothermia was carried out together with the standard treatment protocol according to the European Brain Injury Consortium. Thirty patients with severe head injuries with Glasgow Coma Scale (GCS) score of 3–8 were enrolled into the study. The subjects were divided into two groups. The average age in the hypothermic group of 15 patients was 35 years. The average GCS was 4.5 at the site of accident. Eight patients (53%) sustained associated severe injuries of other organs. The average age of the 15 patients in the normothermic control group was 39 years with an average GCS of 4.3. All the patients in the normothermic group and 11 patients in the hypothermic group underwent neurosurgery, five of them also decompressive craniotomy. Artificial ventilation with continuous monitoring of intracranial pressure (ICP), cerebral perfusion pressure (CPP), arterial blood pressure, jugular bulb oximetry and urinary bladder temperature were instituted in the ICU. Cooling to a core temperature of 34 °C in the hypothermic group was achieved by forced air cooling in combination with circulating-water mattress cooling (Blanketrol II, Cincinnati Sub-Zero) and maintained for 72 h. The difference in the Glasgow Outcome Scale (GOS) between the hypothermic and normothermic groups of patients after 6 months was not statistically significant (P value 0.0843). In the hypothermic group, however, good neurological outcome (GOS 4 and 5) was reached in 13 patients (87%), which represents a 40% increase compared with the normothermic control group in which good neurological outcome was reached in 7 patients (47%). Mean normothermia ICP value of 18±2 mmHg was significantly (P value 0.0007) reduced during mild hypothermia therapy to 12±2 mmHg. Mean normothermia CPP value of 72±3 mmHg significantly increased (P value 0.0007) during this time to 80±4 mmHg with unchanged systolic arterial pressure (P value 0.9013). There were no cardiac or coagulopathy-related complications. Our results showed that mild therapeutic hypothermia could be useful in improving the outcome and neurological recovery in patients with severe head injuries.     

亚低温对重型脑损伤后血清IL-18含量的影响

目的 观察重型创伤性脑损伤(TBI)患者血清白细胞介素18(IL-18)的含量变化.方法 60例患者随机分成常温治疗组和亚低温治疗组,两组均于伤后第1 d、3 d、7 d 和10d 采用酶联免疫吸附(ELISA)法测定血清中IL-18 含量.结果 两组IL-18 含量均高于对照组(P ＜ 0.01).亚低温治疗组IL-18 含量在3d、7 d、10d 低于常温治疗组(P ＜0.01),而在伤后第1 d 差异无统计学意义(P ＞0.05).结论 亚低温治疗能够降低sTBI 患者血清IL-18 含量.     

Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation.

Induction of mild hypothermia improves neurologic outcome after global cerebral ischemia. This study measured levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in hippocampal tissue of rats after resuscitation from 8 minutes of normothermic, asphyxial cardiac arrest. After resuscitation, rats were maintained either at normal temperature (37 degrees C) or cooled to mild hypothermia (33 degrees C, beginning 60 minutes after resuscitation). After 12 or 24 hours, neurotrophin levels in hippocampus were measured by immunoblotting. Ischemia and reperfusion increased hippocampal levels of BDNF. Induction of hypothermia during reperfusion potentiated the increase in BDNF after 24 hours, but not after 12 hours. Levels of NGF were not increased by postresuscitation hypothermia. Hypothermia also increased tissue levels and tyrosine phosphorylation of TrkB, the receptor for BDNF. Increased BDNF levels were correlated with activation of the extracellularly regulated kinase (ERK), a downstream element in the signal transduction cascade induced by BDNF. In contrast to the many deleterious processes during ischemia and reperfusion that are inhibited by induced hypothermia, increasing BDNF levels is a potentially restorative process that is augmented. Increased activation of BDNF signaling is a possible mechanism by which mild hypothermia is able to reduce the neuronal damage typically occurring after cardiac arrest.     

The importance of gender on the beneficial effects of posttraumatic hypothermia

The authors studied the importance of gender on the consequences of mild posttraumatic hypothermia following parasagittal fluid-percussion (F-P) brain injury in rats. After traumatic brain injury (TBI), brain temperature was maintained at normothermia (37 degrees C) or reduced to 33 degrees C for 4 h starting 30 min after the insult followed by a 1.5-h slow rewarming period. Animals (n = 48) were allowed to survive for 3 days before quantitative histopathological and immunocytochemical examination. As previously reported, contusion volume in normothermic animals (37 degrees C) was smaller (P < 0.05) in intact females compared to males. In addition, numbers of NeuN-positive cortical neurons were greater in females versus males after TBI. Posttraumatic hypothermia significantly reduced overall contusion volume in males (P < 0.05), while not significantly reducing contusion volume in females. Likewise, hypothermia protected against the loss of cortical neurons in males but had no effect in females. Ovariectomized females showed contusion volumes and neuronal cell counts comparable to those seen in males as well as a significant reduction in contusion volumes and greater neuronal counts following posttraumatic hypothermia. These data are the first to demonstrate that posttraumatic hypothermia (4 h) does not affect short-term histopathological outcomes in female rats. Potential mechanisms underlying this gender difference are discussed. Finally, these experimental findings may have important implications in terms of clinical trials using therapeutic hypothermia targeting patients with central nervous system (CNS) injury.     

选择性亚低温对急性重型颅脑损伤男性患者红细胞免疫功能的影响

目的 探讨选择性亚低温对急性重型颅脑损伤男性患者红细胞免疫功能的影响.方法 急性重型颅脑损伤男性患者60例,平均分为亚低温组和常温组.常温组给予常规综合治疗,亚低温组在常规综合治疗的基础上给予头颈部选择性亚低温治疗.治疗后1、3、5 d分别取静脉血检测红细胞补体受体1(CR1),红细胞C3b受体花环率(RC3bRR)、红细胞C3b受体免疫复合物花环率(RICR).结果 治疗后5 d亚低温组CR1和RC3bRR均明显高于常温组(P<0.05),而RICR明显低于常温组(P<0.05).亚低温治疗后5 d CR1和RC3bRR明显高于治疗后1和3 d(P<0.05),而RICR明显低于治疗后1和3 d(P<0.05).结论 选择性亚低温治疗后可明显提高急性颅脑损伤男性患者红细胞免疫功能,且随治疗时间的延长红细胞免疫功能水平逐渐增强.     

Acute subdural hematoma without subarachnoid hemorrhage following rupture of a distal anterior cerebral artery aneurysm: a case report]

Acute subdural hematoma (ASDH) without subarachnoid or intracerebral hemorrhage following rupture of an intracranial aneurysm is rare. Only 34 cases of pure ASDH resulting from rupture of an intracranial aneurysm, and 5 cases of pure ASDH secondary to rupture of an anterior cerebral artery (ACA) aneurysm, have been reported in the literature. We report a case of a patient with a ruptured distal ACA aneurysm who presented pure ASDH on CT. A 63-year-old woman was admitted with the acute onset of severe headache, nausea, and dizziness. CT showed a right convexity and interhemispheric ASDH in the absence of subarachnoid or intracerebral hemorrhage. Cerebrospinal fluid was clear by lumbar puncture. However, we still suspected a ruptured intracranial aneurysm as the diagnosis. Angiography was performed and demonstrated a right distal ACA aneurysm with a daughter aneurysm. Evacuation of the subdural hematoma, with the clipping of the aneurysm was performed. Intraoperatively, adhesion between the dome of aneurysm and the falx cerebri was observed. The patient was discharged from the hospital without neurological deficits.     

Therapeutic hypothermia in experimental models of focal and global cerebral ischemia and intracerebral hemorrhage

Experimental evidence shows that therapeutic hypothermia (TH) protects the brain from cerebral injury in multiple ways. In different models of focal and global cerebral ischemia, mild-to-moderate hypothermia reduces mortality and neuronal injury and improves neurological outcome. In models of experimental intracerebral hemorrhage (ICH), TH reduces edema formation but does not show consistent benefi cial effects on functional outcome parameters. However, the number of studies of hypothermia on ICH is still limited. TH is most effective when applied before or during the ischemic event, and its neuroprotective properties vary according to species, strains and the model of ischemia used. Intrinsic changes in body and brain temperature frequently occur in experimental models of focal and global cerebral ischemia, and may have infl uenced studies on other neuroprotectants. This might be one explanation for the failure of a large amount of translational clinical neuroprotective trials. Hypothermia is the only neuroprotective therapeutic agent for cerebral ischemia that has successfully managed the transfer from bench to bedside, and it is an approved therapy for patients after cardiac arrest and children with hypoxic-ischemic encephalopathy. However, the implementation of hypothermia in the treatment of stroke patients is still far from routine clinical practice. In this article, the authors describe the development of TH in different models of focal and global cerebral ischemia, point out why hypothermia is so efficient in experimental cerebral ischemia, explain why temperature regulation is essential for further neuroprotective studies and discuss why TH for acute ischemic stroke still remains a promising but controversial therapeutic option.