Focal epidural cooling reduces the infarction volume of permanent middle cerebral artery occlusion in swine

doi:10.1016/j.surneu.2006.05.064

Surgical Neurology

Volume 67, Issue 2, February 2007, Pages 117-121

https://doi.org/10.1016/j.surneu.2006.05.064 Get rights and content

Abstract

Background

The protective effect against ischemic stroke by systemic hypothermia is limited by the cooling rate and it has severe complications. This study was designed to evaluate the effect of SBH induced by epidural cooling on infarction volume in a swine model of PMCAO.

Methods

Permanent middle cerebral artery occlusion was performed in 12 domestic swine assigned to groups A and B. In group A, the cranial and rectal temperatures were maintained at normal range (37°C-39°C) for 6 hours after PMCAO. In group B, cranial temperature was reduced to moderate (deep brain, <30°C) and deep (brain surface, <20°C) temperature and maintained at that level for 5 hours after 1 hour after PMCAO, by the epidural cooling method. All animals were euthanized 6 hours after MCAO; their brains were sectioned and stained with 2,3,5-triphenyltetrazolium chloride and their infarct volumes were calculated.

Results

The moderate and deep brain temperature (at deep brain and brain surface) can be induced by rapid epidural cooling, whereas the rectal temperature was maintained within normal range. The infarction volume after PMCAO was significantly reduced by epidural cooling compared with controls (13.73% ± 1.82% vs 5.62% ± 2.57%, P < .05).

Conclusions

The present study has demonstrated, with histologic confirmation, that epidural cooling may be a useful strategy for reducing infarct volume after the onset of ischemia.

Introduction

Mortality and morbidity from ischemic stroke are high. The treatment of acute ischemic stroke has been the topic of much research. Neuroprotective agents, including glutamate receptor antagonists, calcium channel blockers, and free-radical scavengers, have shown encouraging results in animal models, but they have not yet been proven to be beneficial clinically [20]. As such, many clinicians and researchers redirected their interest and attention toward hypothermia as a method of cerebral protection.

Artificial hypothermia is widely used in different areas of medicine, and the protective effects of hypothermia against cerebral injury or ischemia have long been recognized in animal models. At present, mild or moderate systemic hypothermia by surface cooling is the most common method of hypothermia used in surgical procedures. However, many studies have reported that it carries the risk of causing complications [32], [34], [36], and a recently published study showed that treatment with mild systemic hypothermia in clinical trials has shown no effect in improving outcomes in severe brain injury [6], [7], [21].

These investigations have emphasized the need for a safer, more effective means of achieving cerebral hypothermia; therefore, SBH was attempted to avoid the complications of systemic cooling. In this study, we have developed a novel method in a porcine model by which selective reduction of brain hypothermia could achieve moderate or deep brain hypothermia. We have investigated the effects of hypothermia with the epidural cooling method on cerebral infarction size and histology in a swine model of PMCAO.

Section snippets

Animal preparation

The experiments were performed on 12 adult male domestic swine, weighing 30 to 35 kg (mean mass, 32.3 ± 1.6 kg), and conducted in accordance with Institutional Policies and Guidelines for the Care and Use of Laboratory Animals. All pigs were denied food overnight but allowed free access to water. Room temperature was maintained by an air conditioner at approximately 18 °C throughout all experiments. After an intraperitoneal injection of atropine sulfate (0.5 mg/kg), anesthesia was mechanically

Results

All animals survived until the end of the experiment. No significant differences in MABP were noted between the groups during the experiment.

Discussion

Time of initiation, duration, and depth of hypothermia are important factors in reducing ischemic infarction volume [9], [16]. Deeper and more rapid hypothermia can achieve better protective effects against ischemic stroke. However, deeper systemic hypothermia (<32°C) through the use of surface cooling with external cooling blankets has not been achieved in clinical practice because of severe side effects, including cardiac arrhythmias, coagulopathy, and immunosuppression [5], [10], [12], [18],

Conclusion

The present study has demonstrated, with histologic confirmation, that epidural cooling may be a useful strategy for reducing infarct volume after the onset of ischemia.

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Cited by (19)

Postcooling But Not Precooling Benefits Motor Recovery by Suppressing Cell Death After Surgical Spinal Cord Injury in Rats
2022, World Neurosurgery
Citation Excerpt :
As such, the concept of regional hypothermia (RH) was introduced. Interests in neurologic applications of RH ensued with promising results; it was shown to reduce infarction in a middle cerebral artery occlusion model,5 improve motor recovery after traumatic spinal cord injury,6 favor neurologic outcome in adult brain injury,7 and reduce perihematomal edema after intracranial hemorrhage.8 Hypothermic interventions have also been widely adopted in cardiothoracic surgeries, with protective benefits in ameliorating cerebral and spinal cord ischemia demonstrated in both laboratory and clinical settings.9
Surgical spinal cord injury (SSCI) is often inevitable in patients with intramedullary lesions. Although regional hypothermia (RH) has been demonstrated neuroprotective, the value of priming RH in SSCI has never been studied. Herein, the authors investigated the impact of pre- and post-RH on neurologic recovery in a clinically relevant model.
An SSCI model was established at T10. RH was conducted by focal 4^oC saline perfusion; room temperature (RT) saline was used as controls. Animals were randomized into 6 groups: SHAM−RT/RH, Pre−RT/RH, and Post−RT/RH. Motor and sensory functions were evaluated using the Basso, Beattie, and Bresnahan rating scale and Plantar test 2 weeks after surgery. TUNEL assay and Fluoro-Jade C staining were conducted to examine the cell death, and the alterations of apoptotic markers including total and cleaved casepase 3, Bcl-2, and Bax, as well as the pyroptotic proteins including NLRP3, ASC, and caspase 1, were determined.
RH perfusion successfully created an intramedullary hypothermia approximately at 24^oC, while RT controls remained above 30^oC. Animals receiving postinjury RH had the least cell death and the best motor performance, while pre-RH showed the most dead cells and worst hind limb movements. Immunoblotting depicted that post-RH suppressed both apoptotic and pyroptotic death as the cleaved/total caspase 3, Bcl-2/Bax ratio, and NLRP3/ASC/caspase 1 signaling were inhibited. Priming cooling, on the contrary, elevated pyroptosis and did not affect apoptosis significantly.
Priming RH before surgical incision could not be supported as it caused excessive cell death. In contrast, instant introduction of RH is beneficial in rescuing neurologic function.
Protective effect against focal cerebral ischemia injury in acute phase of a novel invasive device for regional hypothermia
2015, Journal of the Chinese Medical Association
Citation Excerpt :
Accordingly, methods and devices that provide regional hypothermia have been developed to cool through blood vessels,9–12 nasal cavity,13–18 meninges19–21 and the head.22–27 Unfortunately, the cooling efficiency through brain parenchyma has not been measured in most of those devices, and only a few studies have explored the neuroprotective effects of regional hypothermia.21,28–31 In addition, the optimal temperature range for regional hypothermia is still controversial.28,29,32
Systemic hypothermia is considered beneficial to stroke patients. However, many complications ensue. The aim of this study was to evaluate the effect of a new invasive regional cooling device in cerebral ischemic injury in a rat model.
After a pilot study confirming the efficiency of the cooling device, 15 adult male Sprague–Dawley rats, weighing 300–400 g, were randomly assigned into three groups: cooling device applied at 14°C and at 26°C, and a sham group. Focal cerebral ischemic injury was achieved by electrocauterization of the left middle cerebral artery through craniectomy and temporal occlusion of both common carotid arteries for 3 hours. Within 30 minutes after the end of ischemic injury, the cooling device was inserted into the rat brain through a stereotactic frame to provide regional hypothermia for 2 hours. The rats were sacrificed immediately after the 2-hour regional hypothermia.
Although triphenyltetrazolium chloride staining showed smaller ischemic lesions in both the 26°C and 14°C groups compared to the control group, Fluoro Jade C staining showed no neuroprotective effects in the rostrum cerebral cortex in both groups. However, both triphenyltetrazolium chloride and Fluoro Jade C staining indicated significant beneficial effects in the caudal cerebral cortex in rats with cooling device applied at 26°C compared to the 14°C and control groups.
Our findings indicated that the device can effectively achieve regional hypothermia and could be beneficial for patients with cerebral ischemia during the acute phase.
Neuroprotective effects of focal brain cooling on photochemically-induced cerebral infarction in rats: Analysis from a neurophysiological perspective
2013, Brain Research
Citation Excerpt :
Despite these favorable outcomes, systemic hypothermia can also lead to fatal complications, such as infection, cardiac arrhythmia, and disruption of blood coagulation (Clifton et al., 1993; Marion et al., 1993; Schubert, 1995). To resolve these issues, focal brain cooling (FBC) has recently drawn attention as a minimally invasive treatment for brain injuries (Oku et al., 2009; Wagner et al., 2005; Zhang et al., 2007; Clark et al., 2009). Compared with systemic hypothermia, FBC has the advantage of reducing the cooling temperature below 30 °C, without producing permanent brain damage or systemic complications (Yang et al., 2006).
Although systemic hypothermia provides favorable outcomes in stroke patients, it has only been adopted in a limited number of patients because of fatal complications. To resolve these issues, focal brain cooling (FBC) has recently drawn attention as a less-invasive treatment for brain injuries. Therefore, we investigated whether FBC has a favorable effect on focal cerebral ischemia (FCI). Male-adult-Wistar rats were used. Under general anesthesia, a small burr hole was made and FCI was induced in the primary sensorimotor area (SI-MI) using photothrombosis. An additional craniotomy was made over the SI-MI and FBC was performed at a temperature of 15 °C for 5 h. Electrocorticograms (ECoG) were recorded on the border cortex of the ischemic focus. Thereafter, rats were sacrificed and the infarct area was measured. In another experiment, rats were allowed to recover for 5 days after cooling and neurobehavioral function was evaluated. FBC suppressed all ECoG frequency bands during and after cooling (p<0.05), except for the delta frequency band in the precooling versus rewarming periods. The injured areas in the cooling and non-cooling groups were 0.99±0.30 and 1.71±0.54 mm², respectively (p<0.03). The grip strength at 2 days after surgery was preserved in the cooling group (p<0.05). We report the novel finding that epileptiform discharges were suppressed in the ischemic border, the infarct area was reduced and neurobehaviour was preserved by FBC. These results indicate that FBC is neuroprotective in the ischemic brain and has demonstrated therapeutic potential for cerebral infarction.
The neurophysiological effect of mild hypothermia in gyrencephalic brains submitted to ischemic stroke and spreading depolarizations
2024, Frontiers in Neuroscience
Mild hypothermia reduces spreading depolarizations and infarct size in a swine model
2023, Journal of Cerebral Blood Flow and Metabolism
Magnetic Resonance Imaging and Gait Analysis Indicate Similar Outcomes Between Yucatan and Landrace Porcine Ischemic Stroke Models
2021, Frontiers in Neurology

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IschemiaFocal epidural cooling reduces the infarction volume of permanent middle cerebral artery occlusion in swine

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Animal preparation

Results

Discussion

Conclusion

Br J Anaesth

Resuscitation

Brain Res

J Neurosci Methods

Thromb Res

Reduction by delayed hypothermia of cerebral infarction following middle cerebral artery occlusion in the rat: a time-course study

J Neurosurg

The importance of brain temperature in cerebral ischemic injury

Stroke

Epidural cooling for selective brain hypothermia in porcine model

Acta Neurochir (Wien)

Hypothermia in the sepsis syndrome and clinical outcome: the Methylprednisolone Severe Sepsis Study Group

Crit Care Med

Systemic hypothermia in treatment of brain injury

J Neurotrauma

Lack of effect of induction of hypothermia after acute brain injury

N Engl J Med

Bloodless surgery by means of profound hypothermia and circulatory arrest: effect on brain and heart

Ann Surg

Combination of decompressive craniectomy and mild hypothermia ameliorates infarction volume after permanent focal ischemia in rats

Stroke

Some physiologic effects of short and long term hypothermia upon the liver

Surgery

Effects of intraischemic hypothermia on cerebral damage in a model of reversible focal ischemia

Neurosurgery

Reflections on circulatory control

Lancet

Safety and performance of a novel intravascular catheter for induction and reversal of hypothermia in a porcine model

Neurosurgery

The effect of mild hypothermia on permanent focal ischemia in rat

Neurosurgery

Mild intraischemic hypothermia reduces postischemic hyperperfusion, delayed postischemic hypoperfusion, blood-brain barrier disruption, brain edema, and neuronal damage volume after temporary focal cerebral ischemia in rats

J Cereb Blood Flow Metab

Therapeutic hypothermia for acute ischemic stroke: what do laboratory studies teach us?

Stroke

Ischemia
Focal epidural cooling reduces the infarction volume of permanent middle cerebral artery occlusion in swine