Brain Cooling Research Articles

More than a simple fixed action pattern: Yawning in drills

In the last decade, increasing attention has been devoted to exploring some aspects of yawning in non-human animals. With their chin red mark, bony paranasal swellings, male large brains and long canines, drills (Mandrillus leucophaeus) offer a robust model for testing hypotheses on the phenomenon. We identified two yawn variants (covered, YCT and uncovered teeth, YUCT) which differ in terms of recruitment of muscular action units (AUs). We tested the effects of several variables (sex, dominance rank, context) on the duration of the yawn and the probability of YCT or YUCT occurrence. We found that males performed longer and more YUCT than females. These findings support the Brain Cooling Hypothesis suggesting that those species showing large brains tend to display larger and longer yawns. We also tested the State Changing Hypothesis predicting the presence of a temporal association of yawning and ongoing behavioral transitions. A sequential analysis revealed that after 30 s following a yawn, drills were significantly more likely to change their behavioral state. Through the observation of yawning, conspecifics might gain knowledge of impending state changes. Seeing other’s yawns increased the probability of a similar response in the observers, thus suggesting the presence of yawn contagion in drills. Although the dataset needs to be expanded, our findings indicate that yawning is variable in drills, it can be associated with subjects’ state changes, and the imminent shifts can be perceived/processed by conspecifics.Graphical

878 Selective Brain Cooling is Possible via CSF Exchange With Double Lumen EVD- Proof of Concept in Porcine Model

INTRODUCTION: Hypothermia is seen as neuroprotective after brain insult (BI). In acute phase after BI it affects brain metabolism by decreasing oxygen and glucose consumption. Hypothermia affects apoptosis and inflammatory mediators. In the later stage of BI, enzyme activation stimulates protein and lipid breakdown, which can be slowed and decreased with hypothermia. In the latest stage of BI hypothermia has shown positive affect in angiogenesis, neurogenesis, synaptogenesis. Hypothermia also reduces vasogenic oedema and blood brain barrier dysfunction. Despite hypothermia´s neuroprotective effect randomized control trials have demonstrated its benefits only limited scenarios - mainly in global ischemia (post-cardiac infarction and ischemia of new-born). Majority of complications related to hypothermia has been due to systemic hypothermia and selective brain cooling has never been demonstrated in large mammals without changes in core temperature of subject. METHODS: We inserted double lumen external ventricular drainage (EVD) into the lateral ventricle of porcine. We added spinal drainage to accelerate CSF exchange to cooled NaCl solution. Brain parenchymal temperature was measured from the contralateral brain hemisphere and the ipsilateral brain hemisphere. RESULTS: Contralateral brain hemisphere temperature dropped by 3.1C from baseline while core temperature changed only by 0.5C. Ipsilateral temperature cooled by 7.5C from baseline to 30.8C, while core temperature was 37.7C. Total time needed to achieve selective cooling was 1.5h. Porcine started to have arrhythmias when brain temperature approached 30.8C. CONCLUSIONS: We are first to describe that selective brain cooling is possible via CSF exchange with double lumen EVD to achieve significant temperature difference between body core and brain. The timing and rate of selective cooling needs to be established as cause of arrhythmias before starting human trials.

Numerical Study on the Process of Human Brain Cooling Treated by Hemoperfusion Mild Hypothermia

Mild hypothermia, as a common means of intraoperative nerve protection, has been used in clinical practice. Compared with the traditional methods such as freezing helmet and nasopharyngeal cooling, hypothermic blood perfusion is considered to be a promising treatment for mild hypothermia, but it lacks experimental and theoretical verification of its cooling effect. In this study, the commercial finite element simulation software COMSOL combined the Pennes equation with the cerebrovascular network model to construct a new simplified human brain model, which was further used to simulate the cooling process of cerebral hypothermic blood perfusion. When the hypothermic blood perfusion was 33 ℃, the human brain could enter the mild hypothermic state within 4 minutes. By comparing with helmet cooling, the feasibility and efficiency of the blood perfusion scheme were verified. By comparing with the calculation results based on Pennes equation, the rationality of the model constructed in this study were verified. This model can non-intrusively predict the changes of brain temperature during surgery, and provide a reference for the setting of treatment parameters such as blood temperature, so as to provide personalized realization of safer and more effective mild hypothermia neuro protection.

Variance of Carotid-Rete-Mediated Selective Brain Cooling Across Aridity Indices

Species-environment interactions are integral to survivorship, especially when those environments test the extremes of organismal physiology. Large-bodied (>50kg) mammals, specifically artiodactyls and feliform carnivores, possess a specialized physiology known as carotid-rete-mediated selective brain cooling (CR-SBC), which has been established to be selectively advantageous in environments where water availability is limited and risk for dehydration is high. In this study, we investigate whether CR-SBC provides a release from physiological constraint imposed by the environment, specifically aridity. Using 18O values from tooth enamel as a proxy for water metabolism, we model the range in variance across 1265 individuals from species that possess a carotid rete against those without from three different environmental categories – arid, dry subhumid, and humid – using a non-parametric ANOVA. The results of the analysis indicate there is a comparatively higher, and statistically significant, amount of variance of 18O in mammals possessing CR-SBC than those without, especially within arid climates, that begins to equalize as environmental water availability increases. As environments become increasingly arid, understanding which species are more vulnerable to shifts in climate becomes more pertinent. The presence of CR-SBC provides a clear, binary feature by which to measure the relationship between the environment and species survivorship under varying levels of water availability, and is useful in informing and improving conservation tools, such as physiological distribution models.

Selective Brain Cooling: A New Horizon of Neuroprotection.

Therapeutic hypothermia (TH), which prevents irreversible neuronal necrosis and ischemic brain damage, has been proven effective for preventing ischemia-reperfusion injury in post-cardiac arrest syndrome and neonatal encephalopathy in both animal studies and clinical trials. However, lowering the whole-body temperature below 34°C can lead to severe systemic complications such as cardiac, hematologic, immunologic, and metabolic side effects. Although the brain accounts for only 2% of the total body weight, it consumes 20% of the body's total energy at rest and requires a continuous supply of glucose and oxygen to maintain function and structural integrity. As such, theoretically, temperature-controlled selective brain cooling (SBC) may be more beneficial for brain ischemia than systemic pan-ischemia. Various SBC methods have been introduced to selectively cool the brain while minimizing systemic TH-related complications. However, technical setbacks of conventional SBCs, such as insufficient cooling power and relatively expensive coolant and/or irritating effects on skin or mucosal interfaces, limit its application to various clinical settings. This review aimed to integrate current literature on SBC modalities with promising therapeutic potential. Further, future directions were discussed by exploring studies on interesting coping skills in response to environmental or stress-induced hyperthermia among wild animals, including mammals and birds.

A Numerical Study on Microgap-Based Focal Brain Cooling Device to Mitigate Hotspot for the Treatment of Epileptic Seizure

Abstract Epilepsy is a common chronic neurological disorder characterized by abnormally excessive and synchronized brain cell activities causing seizures. For proper functioning of the brain, epilepsy should be diagnosed with existing treatments such as medication therapy, lorazepam, benzodiazepine drug intake, and surgery. However, 30–40% of people continue to have a seizure because of the available treatments. So, the focal brain cooling device (FBC) is a new alternative cooling method in which affected brain tissue is cooled to suppress unprovoked seizures. The present numerical study investigates the cooling effectiveness by adding three different structured titanium micro pin fins in the existing base model. A finite volume-based software fluent-15.0 is used to perform transient heat transfer analysis and flow hydrodynamics. The numerical results obtained show that the temperature distribution is found and more uniform and diamond-structured micro pin fin takes less than 7 min to reach below 15 °C, which is desirable to diminish the high-frequency and high-amplitude epileptic discharges.

A Clinical Test for a Newly Developed Direct Brain Cooling System for the Injured Brain and Pattern of Cortical Brainwaves in Cooling, Noncooling, and Dead Brain.

To ensure the direct delivery of therapeutic hypothermia at a selected constant temperature to the injured brain, a newly innovated direct brain cooling system was constructed. The practicality, effectiveness, and safety of this system were clinically tested in our initial series of 14 patients with severe head injuries. The patients were randomized into two groups: direct brain cooling at 32°C and the control group. All of them received intracranial pressure (ICP), focal brain oxygenation, brain temperature, and direct cortical brainwave monitoring. The direct brain cooling group did better in the Extended Glasgow Outcome Scale at the time of discharge and at 6 months after trauma. This could be owing to a trend in the monitored parameters; reduction in ICP, increment in cerebral perfusion pressure, optimal brain redox regulation, near-normal brain temperature, and lessening of epileptic-like brainwave activities are likely the reasons for better outcomes in the cooling group. Finally, this study depicts interesting cortical brainwaves during a transition time from being alive to dead. It is believed that the demonstrated cortical brainwaves follow the principles of quantum physics.

Optimal Design of Neuroprotective Focal Brain Cooling Device Using Surrogate Model Approach

Focal brain cooling (FBC) is a treatment for refractory epilepsy to suppress epileptic discharges from an epileptic focus. Our wearable FBC system under development consists of a recirculating coolant apparatus and a battery located extracorporeally, and a cooling device made of titanium with water channels inside which is embedded in the skull. An optimal channel design of the cooling device is needed to cool the brain efficiently. Although clinical and animal studies are required to design the cooling device, the number of experiments should be reduced, and finite element (FE) simulation be utilized instead. However, trial-and-error simulations impose a heavy computational burden. One option to deal with this problem is to use surrogate modeling, which is a data-driven approach that mimics the behavior of simulation models with a low computational burden. We optimized the channel structure by combining the surrogate model approach and non-dominated sorting genetic algorithm II (NSGA-II), which is a multi-objective optimization algorithm. The objective was to design a cooling device that simultaneously achieves high cooling performance and low pressure drop since low pressure loss contributes to miniaturization and energy saving of the recirculating apparatus. The optimization result showed that pressure loss was reduced by 28.7% in comparison with the design variables determined through experiments without deteriorating the cooling performance.

Abstract 100: Neuroprotection Provided by Transnasal Airflow-Induced Brain Cooling in a Model of Pediatric Cardiac Arrest

Introduction: High transnasal airflow at ambient temperature increases evaporative cooling of the nasal passages and drives a countercurrent heat exchange between cooled venous blood draining the nasal turbinates with cephalic arterial blood. Hypothesis: High transnasal airflow is not inferior to standard surface cooling in protecting the brain in an infant swine model of asphyxic cardiac arrest. Methods: Arterial O2 saturation was decreased to ~35% for 45 min followed by 7 min airway occlusion to produce asphyxic cardiac arrest in 2-week-old anesthetized piglets (4 kg). Viable neuronal counts were assessed at 6 days of recovery in 6 groups (n=5-9): 1) sham surgery, 2) normothermic recovery, 3) surface cooling to decrease rectal temperature from 38.5 to 34C between 10-120 min 4) transnasal cooling with airflow of 32 L/min from 10-120 min, 5) surface cooling onset delayed until 120 min ROSC, and 6) transnasal cooling delayed by 120 min ROSC. In all 4 cooling groups, hypothermia was sustained at 34C with surface cooling until 20 h ROSC followed by 6-8 h of rewarming. Results: Nasal airflow of 32 L/min decreased brain temperature from 38.3±0.3°C to 33.8±0.6 within 60 min without spatial temperature gradients in these 45-g brains. Surface cooling and transnasal airflow rescued the number of viable neurons in putamen from 38±23% (% of sham viable neurons; ±SD) in the normothermic group to 67±33% and 76±36%, respectively, when initiated at 10 min ROSC, and to 72±30% and 61±25%, respectively, when initiated at 120 min. In sensorimotor cortex, surface cooling and transnasal airflow rescued neurons from 56±36% in the normothermic group to 89±37% and 89±29%, respectively, when initiated at 10 min ROSC, and to 84±19% and 81±28%, respectively, when initiated at 120 min. Conclusions: The use of a high transnasal airflow is as effective as standard surface cooling when initiated at 10 or 120 min after ROSC in protecting vulnerable putamen and sensorimotor cortex from asphyxic cardiac arrest in infant piglets. Because of its simplicity, portability, and low cost, we postulate that transnasal cooling potentially could be deployed in the field by first responders for early initiation of brain cooling prior to maintenance with standard surface cooling after pediatric cardiac arrest.

Inducing Brain Cooling Without Core Temperature Reduction in Pigs Using a Novel Nasopharyngeal Method: An Effectiveness and Safety Study.

BackgroundAcute brain lesions constitute an alarming public health concern. Neuroprotective therapies have been implemented to stabilize, prevent, or reduce brain lesions, thus improving neurological outcomes and survival rates. Hypothermia is the most effective approach, mainly attributed to the reduction in cellular metabolic activity. Whole-body cooling is currently implemented by healthcare professionals; however, adverse events are frequent, limiting the potential benefits of therapeutic hypothermia. Therefore, selective methods have been developed to reduce adverse events while delivering neuroprotection. Nasopharyngeal approaches are the safest and most effective methods currently considered. Our primary objective was to determine the effects of a novel nasopharyngeal catheter on the brain temperature of pigs.MethodsIn this prospective, non-randomized, interventional experimental trial, 10 crossbred pigs underwent nasopharyngeal cooling for 60 min followed by 15 min of rewarming. Nasopharyngeal catheters were inserted into the left nostril and properly positioned at the nasopharyngeal cavity.ResultsNasopharyngeal cooling was associated with a decrease in brain temperature, which was more significant in the left cerebral hemisphere (p = 0.01). There was a reduction of 1.47 ± 0.86 °C in the first 5 min (p < 0.001), 2.45 ± 1.03 °C within 10 min (p < 0.001), and 4.45 ± 1.36 °C after 1 h (p < 0.001). The brain-core gradient was 4.57 ± 0.87 °C (p < 0.001). Rectal, esophageal, and pulmonary artery temperatures and brain and systemic hemodynamic parameters, remained stable during the procedure. Following brain cooling, values of oxygen partial pressure in brain tissue significantly decreased. No mucosal lesions were detected during nasal, pharyngeal, or oral inspection after nasopharyngeal catheter removal.ConclusionsIn this study, a novel nasopharyngeal cooling catheter effectively induced and maintained exclusive brain cooling when combined with effective counter-warming methods. Exclusive brain cooling was safe with no device-related local or systemic complications and may be desired in selected patient populations.

Non-invasive Monitoring of Brain Temperature during Rapid Selective Brain Cooling by Zero-Heat-Flux Thermometry

Introduction: Selective brain cooling can minimize systemic complications associated with whole body cooling but maximize neuroprotection. Recently, we developed a non-invasive, portable and inexpensive system for selectively cooling the brain rapidly and demonstrated its safety and efficacy in porcine models. However, the widespread application of this technique in the clinical setting requires a reliable, non-invasive and accurate method for measuring local brain temperature so that cooling and rewarming rates can be controlled during targeted temperature management. In this study, we evaluate the ability of a zero-heat-flux SpotOn sensor, mounted on three different locations, to measure brain temperature during selective brain cooling in a pig model. Computed Tomography (CT) was used to determine the position of the SpotOn patches relative to the brain at different placement locations.Methods and Results: Experiments were conducted on two juvenile pigs. Body temperature was measured using a rectal temperature probe while brain temperature with an intraparenchymal thermocouple probe. A SpotOn patch was taped to the pig’s head at three different locations: 1-2 cm posterior (Location #1, n=1), central forehead (Location #2, n=1); and 1-2 cm anterior and lateral to the bregma i.e., above the eye on the forehead (Location #3, n=1). This cooling system was able to rapidly cool the brain temperature to 33.7 ± 0.2°C within 15 minutes, and maintain the brain temperature within 33-34°C for 4-6 hours before slowly rewarming to 34.8 ± 1.1°C from 33.7 ± 0.2°C, while maintaining the core body temperature (as per rectal temperature probe) above 36°C. We measured a mean bias of -1.1°C, -0.2°C and 0.7°C during rapid cooling in induction phase, maintenance and rewarming phase, respectively. Amongst the three locations, location #2 had the highest correlation (R2 = 0.8) between the SpotOn sensor and the thermocouple probe.Conclusions: This SBC method is able to tightly control the rewarming rate within 0.52 ± 0.20°C/h. The SpotOn sensor placed on the center of the forehead provides a good measurement of brain temperature in comparison to the invasive needle probe.

Limitations of Local Brain Cooling on Generalized Motor Seizures from Unknown Foci in Awake Rats.

Local brain cooling of an epileptic focus at 15°C reduces the number of spikes on an electrocorticogram (ECoG), terminates seizures, and maintains neurological functions. In this study, we attempted to suppress generalized motor seizures (GMSs) by cooling a unilateral sensorimotor area. GMSs were induced in rats by intraperitoneal injection of bicuculline methiodide, an antagonist of gamma-aminobutyric acid. While monitoring the ECoG and behavior, the right sensorimotor cortex was cooled for 10 min using an implanted device. The number of spikes recorded from the cooled cortex significantly decreased to 71.2% and 62.5% compared with the control group at temperatures of 15 and 5°C (both P <0.01), respectively. The number of spikes recorded from the contralateral mirror cortex reduced to 61.7% and 62.7% (both P <0.05), respectively. The ECoG power also declined to 85% and 50% in the cooled cortex, and to 94% and 49% in the mirror cortex by the cooling at 15 and 5°C, respectively. The spikes regained in the middle of the cooling period at 15°C and in the late period at 5°C. Seizure-free durations during the 10-min periods of cooling at 15 and 5°C lasted for 4.1 ± 2.2 and 5.9 ± 1.1 min, respectively. Although temperature-dependent seizure alleviation was observed, the effect of local cortical cooling on GMSs was limited compared with the effect of local cooling of the epileptic focus on GSMs.

Selective Brain Cooling Reduces Motor Deficits Induced by Combined Traumatic Brain Injury, Hypoxemia and Hemorrhagic Shock.

Selective brain cooling (SBC) can potentially maximize the neuroprotective benefits of hypothermia for traumatic brain injury (TBI) patients without the complications of whole body cooling. We have previously developed a method that involved extraluminal cooling of common carotid arteries, and demonstrated the feasibility, safety and efficacy for treating isolated TBI in rats. The present study evaluated the neuroprotective effects of 4-h SBC in a rat model of penetrating ballistic-like brain injury (PBBI) combined with hypoxemic and hypotensive insults (polytrauma). Rats were randomly assigned into two groups: PBBI+polytrauma without SBC (PHH) and PBBI+polytrauma with SBC treatment (PHH+SBC). All animals received unilateral PBBI, followed by 30-min hypoxemia (fraction of inspired oxygen = 0.1) and then 30-min hemorrhagic hypotension (mean arterial pressure = 40 mmHg). Fluid resuscitation was given immediately following hypotension. SBC was initiated 15 min after fluid resuscitation and brain temperature was maintained at 32–33°C (core temperature at ~36.5°C) for 4 h under isoflurane anesthesia. The PHH group received the same procedures minus the cooling. At 7, 10, and 21 days post-injury, motor function was assessed using the rotarod task. Cognitive function was assessed using the Morris water maze at 13–17 days post-injury. At 21 days post-injury, blood samples were collected and the animals were transcardially perfused for subsequent histological analyses. SBC transiently augmented cardiovascular function, as indicated by the increase in mean arterial pressure and heart rate during cooling. Significant improvement in motor functions were detected in SBC-treated polytrauma animals at 7, 10, and 21 days post-injury compared to the control group (p < 0.05). However, no significant beneficial effects were detected on cognitive measures following SBC treatment in the polytrauma animals. In addition, the blood serum and plasma levels of cytokines interleukin-1 and −10 were comparable between the two groups. Histological results also did not reveal any between-group differences in subacute neurodegeneration and astrocyte/ microglial activation. In summary, 4-h SBC delivered through extraluminal cooling of the common carotid arteries effectively ameliorated motor deficits induced by PBBI and polytrauma. Improving cognitive function or mitigating subacute neurodegeneration and neuroinflammation might require a different cooling regimen such as extended cooling, a slow rewarming period and a lower temperature.

Selective Brain Cooling with Transnasal Flow of Ambient Air for Pediatric Resuscitation

Discharge rates and neurologic outcome from out‐of‐hospital pediatric cardiac arrest remains poor. The recent THAPCA trial for out‐of‐hospital pediatric cardiac arrest reported only a small, non‐significant favorable outcome with hypothermic treatment. A major limitation of this study was the median 5.9‐hour delay in inducing hypothermia, as studies in animals show loss of efficacy with this delay in initiation of hypothermia. To minimize this delay, we developed a simple yet innovative technique of transnasal cooling. Air at ambient temperature is passed through standard nasal cannula and out of the mouth to produce evaporative cooling of the nasal passages and a countercurrent heat exchange with cephalic arterial blood. We determined whether an age‐dependent effect exists in the ability to cool the brain because of potential differences in air humidification capacity during development. We studied piglets at 2–5 days of age (1.8 kg; 40 g brain weight), 2 weeks of age (4 kg; 45 g brain weight) and 6 weeks of age (16 kg; 75 g brain weight; adult brain = 110 g). The corresponding nasal turbinate surface area was estimated to be 3176±243, 4847±417, and 8651±1234 mm2. In anesthetized 1.8‐kg piglets with mechanical ventilation and an open mouth to permit airflow exit, institution of nasal airflow of 4 L/min through nasal cannula decreased brain temperature from 38.0±0.4°C to 36.4±0.9, 35.6±1.2, and 34.4±1.7°C at 30, 60, and 120 min, respectively. In 4‐kg piglets, nasal airflow of 32 L/min decreased brain temperature from 38.3±0.3°C to 35.0±0.6, 33.8±0.6, and 31.9±0.6°C at 30, 60, and 120 min, respectively. In 16‐kg piglets, nasal airflow of 32 L/min decreased brain temperature from 38.5±0.4°C to 35.1±1.6, 34.1±1.8, and 32.9±1.6°C at 30, 60, and 120 min, respectively. No further benefit was seen by increasing airflow to 48 L/min. No substantial spatial temperature gradients were seen among the sensory cortex, putamen, thalamus, cerebellum and olfactory bulb in any age group, suggesting that heat transfer is via blood convection rather than direct conduction from the airway wall. Decreases in rectal temperature lagged brain temperature by 30–60 min at all three ages. The rapid and selective brain cooling indicates that a high humidifying capacity of the nasal turbinates is present early in life. Because of its simplicity, portability, and low cost, transnasal cooling potentially could be deployed in the field by emergency medical technicians, in both community hospital emergency rooms, and in low resource areas for early initiation of brain cooling prior to maintenance with standard surface cooling after pediatric cardiac arrest.Support or Funding InformationSupported by NIH NS095036This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Influence of Brain Cooling on Frequency Characteristics of the Epileptic Focus and Its Surrounding Area

Influence of Brain Cooling on Frequency Characteristics of the Epileptic Focus and Its Surrounding Area

Hypothesis to Explain Yawning, Cortisol Rise, Brain Cooling and Motor Cortex Involvement of Involuntary Arm Movement in Neurologically Impaired Patients

Association between the hormone cortisol and yawning has been found. The Thompson Cortisol Hypothesis proposed a link between yawning and rises in cortisol with further recent evidence from neuroscience showing communication between the motor cortex, brain-stem and hypothalamus. Hormonal and neuronal links form the proposed network that influences and also monitors cortisol and brain temperature regulation via the hypothalamus. Evidence supports the proposed connection between brain-stem, hypothalamus and motor cortex and further supports the Thompson Cortisol Hypothesis suggesting threshold levels of cortisol elicit yawning to cool the brain. Additionally, this may explain the well-known observed phenomenon known as parakinesia brachialis oscitans in brain-stem ischaemic stroke patients during involuntary yawning.

Abstract TP8: A Pilot Study of Selective Brain Cooling by Intra-arterial Infusion of Cold Saline in Acute Ischemic Stroke

Background and purpose: The neuroprotection of hypothermia in acute ischemic stroke has been proved by many animal experiments. However, the whole body cooling needs relatively longer time to reach target temperature and has many adverse effects. In this trial, we focused on the feasibility and safety of selective brain cooling by intra-arterial infusion of cold saline in patients with acute ischemic stroke during endovascular revascularization procedure. Methods: Patients who suffered from large proximal vessel occlusions within 8 hours after symptoms onset were enrolled. All patients received intra-arterial recanalization combined with infusion of isotonic saline (4°C) into ischemic territory through angiographic catheter. Vital signs, physiological parameters, adverse effects and complications were analyzed to evaluate feasibility and safety. Modified Rankin Scale (mRS) and mortality at 3 months were analyzed to evaluate clinical outcome. Results: 26 patients with a mean age of 58.4±9.56 years and median NIHSS score of 18 (14-20) were enrolled. The median time from symptoms onset to groin puncture was 383 (195-432) minutes. physiologic parameters were relatively stable before, during, and after revascularization procedures. The temperature of ischemic cerebral tissue was dropped at least 2°C theoretically during infusion of the cold solution, and rectal temperature was mildly dropped (maximum 0.3°C), but soon returned to normal after infusion. Complications in these patients included pneumonia (n=10), mild vascular spasm (n=4), melena (n=2), deep vein thrombosis (n=1), coagulation disorder (n=2). No intracranial hemorrhage, shivering, groin hematom, acute congestive heart failure, renal inadequacy, platelet count&lt;100 000/nL and arrhythmia were observed. At 3 months, 15 patients had good outcome (mRS, 0-2) and 11 patients with poor outcome (mRS, 3-6). Conclusions: Selective brain cooling by intra-arterial infusion of cold saline combined with endovascular recanalization therapy in acute ischemic stroke is feasible and safe.

Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats.

ObjectiveThe purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI.Materials and MethodsThirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain.ResultsPermeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min-1 vs. 0.07 ± 0.02 min-1, p = 0.661 for Ktrans; 0.30 ± 0.05 min-1 vs. 0.37 ± 0.11 min-1, p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05).ConclusionLocalized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group.

Efficacy of Selective Brain Cooling Using a Nasopharyngeal Method in Piglets.

Mild hypothermia is an effective neuroprotective strategy for a variety of acute brain injuries. Cooling the nasopharynx may offer the capability to cool the brain selectively due to anatomic proximity of the internal carotid artery to the cavernous sinus. This study investigated the feasibility and efficiency of nasopharyngeal brain cooling by continuously blowing room temperature or cold air at different flow rates into the nostrils of normal newborn piglets. Experiments were conducted on thirty piglets (n = 30, weight = 2.7 ± 1.5 kg). Piglets were anesthetized with 1–2% isoflurane and were randomized to receive one of four different nasopharyngeal cooling treatments: I. Room temperature at a flow rate of 3–4 L min(−1) (n = 6); II. −1 ± 2 °C at a flow rate of 3–4 L min(−1) (n = 6); III. Room temperature at a flow rate of 14–15 L min(−1) (n = 6); IV. −8 ± 2 °C at a flow rate of 14–15 L min(−1) (n = 6). To control for the normal thermal regulatory response of piglets without nasopharyngeal cooling, a control group of piglets (n = 6) had their brain temperature monitored without nasopharyngeal cooling. The duration of treatment was 60 min, with additional 30 min of observation. In group I, median cooling rate was 1.7 ± 0.9 °C/h by setting the flow rate of room temperature air to 3–4 L min(−1). Results of comparing different temperatures and flow rates in the nasopharyngeal cooling approach reveal that the brain temperature could be reduced rapidly at a rate of 5.5 ± 1.1 °C/h by blowing −8 ± 2 °C air at a flow rate of 14–15 L min(−1). Nasopharyngeal cooling via cooled insufflated air can lower the brain temperature, with higher flows and lower temperatures of insufflated air being more effective.

Selective Cooling of the Brain in Newborn Piglets and Rabbits Using a Novel Nasopharyngeal Method

Mild hypothermia has become an effective neuroprotective strategy following head trauma, cardiac arrest and neonatal asphyxia. However, cooling the whole body below 33-34°C can induce severe complications; therefore, selective brain cooling (SBC) could minimize adverse effects by maintaining core body temperature at normal values over an extended period of time. Recently, we developed a novel method of SBC and demonstrated its safety and efficacy in a piglet model. the method was based on spraying room temperature or cold air into the nostrils at different flow rates. Pigs possess a carotid rete (a set of small parallel arteries) which is surrounded by the cavernous sinus; together these serve as an effective heat exchanger for the brain. However, in mammals in which the carotid rete is missing such as rabbits and humans, some suggest that there is no effective heat exchange in the cavernous sinus and, consequently, SBC is not efficient in these species. OBJECTIVE To evaluate the effectiveness of this approach on rabbits and compare it with previous finding on newborn piglets.