Treatments (12 and 48 h) with systemic and brain-selective hypothermia techniques after permanent focal cerebral ischemia in rat

Clark, Darren L.; Penner, Mark; Wowk, Shannon; Orellana-Jordan, Ian M.; Colbourne, Frederick

doi:10.1016/j.expneurol.2009.10.002

Cited by 46 publications

(33 citation statements)

References 56 publications

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“…However, SBC failed to protect against cognitive dysfunction or mitigate brain tissue damage out to 21 DPI, suggesting that enduring protection may require more prolonged exposure to SBC. In keeping with this, studies of ischemic brain injury have shown that an even 12-hours brain cooling duration failed to mitigate behavioral impairment and infarct size measured at 1 month after permanent middle cerebral artery occlusion, whereas significant beneficial effects were achieved by 48 hours brain cooling (Clark et al, 2009). The use of b-APP and silver staining in this study demonstrated a temporal profile of axonal injury following PBBI, which appeared to respond to the immediate SBC treatments differently.…”

Section: Discussionsupporting

confidence: 70%

Comprehensive Evaluation of Neuroprotection Achieved by Extended Selective Brain Cooling Therapy in a Rat Model of Penetrating Ballistic-Like Brain Injury

Shear

Deng-Bryant

et al. 2016

Therapeutic Hypothermia and Temperature Management

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Brain hypothermia has been considered as a promising alternative to whole-body hypothermia in treating acute neurological disease, for example, traumatic brain injury. Previously, we demonstrated that 2-hours selective brain cooling (SBC) effectively mitigated acute (p24 hours postinjury) neurophysiological dysfunction induced by a penetrating ballistic-like brain injury (PBBI) in rats. This study evaluated neuroprotective effects of extended SBC (4 or 8 hours in duration) on sub-acute secondary injuries between 3 and 21 days postinjury (DPI). SBC (34°C) was achieved via extraluminal cooling of rats' bilateral common carotid arteries (CCA). Depending on the experimental design, SBC was introduced either immediately or with a 2-or 4-hour delay after PBBI and maintained for 4 or 8 hours. Neuroprotective effects of SBC were evaluated by measuring brain lesion volume, axonal injury, neuroinflammation, motor and cognitive functions, and post-traumatic seizures. Compared to untreated PBBI animals, 4 or 8 hours SBC treatment initiated immediately following PBBI produced comparable neuroprotective benefits against PBBI-induced early histopathology at 3 DPI as evidenced by significant reductions in brain lesion volume, axonal pathology (beta-amyloid precursor protein staining), neuroinflammation (glial fibrillary acetic protein stained-activated astrocytes and rat major histocompatibility complex class I stained activated microglial cell), and post-traumatic nonconvulsive seizures. In the later phase of the injury (7-21 DPI), significant improvement on motor function (rotarod test) was observed under most SBC protocols, including the 2-hour delay in SBC initiation. However, SBC treatment failed to improve cognitive performance (Morris water maze test) measured 13-17 DPI. The protective effects of SBC on delayed axonal injury (silver staining) were evident out to 14 DPI. In conclusion, the CCA cooling method of SBC produced neuroprotection measured across multiple domains that were evident days/weeks beyond the cooling duration and in the absence of overt adverse effects. These ''proof-of-concept'' results suggest that SBC may provide an attractive neuroprotective approach for clinical considerations.

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Section: Discussionsupporting

confidence: 70%

Comprehensive Evaluation of Neuroprotection Achieved by Extended Selective Brain Cooling Therapy in a Rat Model of Penetrating Ballistic-Like Brain Injury

Shear

Deng-Bryant

et al. 2016

Therapeutic Hypothermia and Temperature Management

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“…7,8 When the severity of the ischemic insult increases or when the onset of cooling is delayed, it is conversely well established that prolonging hypothermia is critical for achieving a maximal neurological protection. 27,28 For example, prolonged cooling provided enduring behavioral and histological protection in rats submitted to permanent middle cerebral artery occlusion, even when delayed after the onset of ischemia. 27 Another important beneficial effect of hypothermic TLV is the cardioprotection observed here like that previously shown in animal models of coronary artery occlusion.…”

Section: Chenoune Et Al Liquid Ventilation Hypothermia and Cardiac mentioning

confidence: 99%

“…27,28 For example, prolonged cooling provided enduring behavioral and histological protection in rats submitted to permanent middle cerebral artery occlusion, even when delayed after the onset of ischemia. 27 Another important beneficial effect of hypothermic TLV is the cardioprotection observed here like that previously shown in animal models of coronary artery occlusion. 11,17,18 This was especially observed after 10 minutes of cardiac arrest because myocardial lesions were minor in the groups submitted to only 5 minutes of cardiac arrest.…”

Section: Chenoune Et Al Liquid Ventilation Hypothermia and Cardiac mentioning

confidence: 99%

Ultrafast and Whole-Body Cooling With Total Liquid Ventilation Induces Favorable Neurological and Cardiac Outcomes After Cardiac Arrest in Rabbits

et al. 2011

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Background-In animal models of cardiac arrest, the benefit afforded by hypothermia is closely linked to the rapidity of the decrease in body temperature after resuscitation. Because total liquid ventilation (TLV) with temperature-controlled perfluorocarbons induces a very rapid and generalized cooling, we aimed to determine whether this could limit the post-cardiac arrest syndrome in a rabbit model. We especially focused on neurological, cardiac, pulmonary, liver and kidney dysfunctions. Methods and Results-Anesthetized rabbits were submitted to either 5 or 10 minutes of untreated ventricular fibrillation.After cardiopulmonary resuscitation and resumption of a spontaneous circulation, the animals underwent either normothermic life support (control) or therapeutic hypothermia induced by TLV. The latter procedure decreased esophageal and tympanic temperatures to 32°C to 33°C within only 10 minutes. After rewarming, the animals submitted to TLV exhibited an attenuated neurological dysfunction and decreased mortality 7 days later compared with control. The neuroprotective effect of TLV was confirmed by a significant reduction in brain histological damages. We also observed limitation of myocardial necrosis, along with a decrease in troponin I release and a reduced myocardial caspase 3 activity, with TLV. The beneficial effects of TLV were directly related to the rapidity of hypothermia induction because neither conventional cooling (cold saline infusion plus external cooling) nor normothermic TLV elicited a similar protection. Conclusions-Ultrafast cooling instituted by TLV exerts potent neurological and cardiac protection in an experimental model of cardiac arrest in rabbits. This could be a relevant approach to provide a global and protective hypothermia against the post-cardiac arrest syndrome. (Circulation. 2011;124:901-911.)Key Words: cardiopulmonary resuscitation Ⅲ fibrillation Ⅲ heart arrest Ⅲ ischemia Ⅲ ventilation I nstitution of mild therapeutic hypothermia (32°C to 34°C) during 24 to 36 hours after resuscitation is known to improve survival and neurological recovery in comatose survivors of cardiac arrest. 1,2 However, experimental studies in dogs, 3,4 pigs, 5,6 and rodents 7,8 demonstrated that the neuroprotection afforded by hypothermia was related to the rapidity of the decrease in body temperature after resuscitation. When achieved rapidly, hypothermia could also be beneficial for other organs because, for example, it can also be potently cardioprotective during myocardial ischemia. 9 -12 Accordingly, many strategies were proposed to afford such a rapid hypothermia, including intravenous infusion of cold fluid 13 and endovascular 14 or intranasal cooling. 15,16 Clinical Perspective on p 911Another strategy that can experimentally provide very rapid and generalized cooling is liquid ventilation of the lungs with temperature-controlled perfluorocarbons. 11,[17][18][19][20][21][22] These liquids can use the lungs as heat exchangers while maintaining normal gas exchanges. 18 -20 In addition, this ven...

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“…Their study showed a marked decrease in intercranial pressure in 62 out of 64 patients within 4 hours of induction of hypothermia (Polderman et al, 2002). Another study by Clark et al (2009) conducted 12 and 48 hours of general hypothermia (33°C) in adult rats 1 hour after permanent middle cerebral artery occlusion, a permanent stroke model. A significant reduction in lesion volume, behavioral, and functional impairment, such as that involving skilled reaching ability as well as enduring histological improvement, was observed in the hypothermia treatment groups (Clark et al, 2009).…”

Section: Discussionmentioning

confidence: 98%

“…Another study by Clark et al (2009) conducted 12 and 48 hours of general hypothermia (33°C) in adult rats 1 hour after permanent middle cerebral artery occlusion, a permanent stroke model. A significant reduction in lesion volume, behavioral, and functional impairment, such as that involving skilled reaching ability as well as enduring histological improvement, was observed in the hypothermia treatment groups (Clark et al, 2009). Numerous factors, such as the duration of hypothermia as well as the method of hypothermia employed, can determine the outcomes.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Local and General Hypothermia on Temperature Profiles of the Central Nervous System Following Spinal Cord Injury in Rats

Bazley

Pashai²,

Kerr

et al. 2014

Therapeutic Hypothermia and Temperature Management

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Local and general hypothermia are used to treat spinal cord injury (SCI), as well as other neurological traumas. While hypothermia is known to provide significant therapeutic benefits due to its neuroprotective nature, it is unclear how the treatment may affect healthy tissues or whether it may cause undesired temperature changes in areas of the body that are not the targets of treatment. We performed 2-hour moderate general hypothermia (32°C core) or local hypothermia (30°C spinal cord) on rats that had received either a moderate contusive SCI or laminectomy (control) while monitoring temperatures at three sites: the core, spinal cord, and cortex. First, we identified that injured rats that received general hypothermia exhibited larger temperature drops at the spinal cord (-3.65°C, 95% confidence intervals [CIs] -3.72, -3.58) and cortex ( -3.64°C, CIs -3.73, -3.55) than uninjured rats (spinal cord: -3.17°C, CIs -3.24, -3.10; cortex: -3.26°C, CIs -3.34, -3.17). This was found due to elevated baseline temperatures in the injured group, which could be due to inflammation. Second, both general hypothermia and local hypothermia caused a significant reduction in the cortical temperature (-3.64°C and -1.18°C, respectively), although local hypothermia caused a significantly lower drop in cortical temperature than general hypothermia ( p < 0.001). Lastly, the rates of rewarming of the cord were not significantly different among the methods or injury groups that were tested; the mean rate of rewarming was 0.13 -0.1°C/ min. In conclusion, local hypothermia may be more suitable for longer durations of hypothermia treatment for SCI to reduce temperature changes in healthy tissues, including the cortex.

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Treatments (12 and 48 h) with systemic and brain-selective hypothermia techniques after permanent focal cerebral ischemia in rat

Cited by 46 publications

References 56 publications

Comprehensive Evaluation of Neuroprotection Achieved by Extended Selective Brain Cooling Therapy in a Rat Model of Penetrating Ballistic-Like Brain Injury

Comprehensive Evaluation of Neuroprotection Achieved by Extended Selective Brain Cooling Therapy in a Rat Model of Penetrating Ballistic-Like Brain Injury

Ultrafast and Whole-Body Cooling With Total Liquid Ventilation Induces Favorable Neurological and Cardiac Outcomes After Cardiac Arrest in Rabbits

The Effects of Local and General Hypothermia on Temperature Profiles of the Central Nervous System Following Spinal Cord Injury in Rats

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