Comparative neuroprotective efficacy of prolonged moderate intraischemic and postischemic hypothermia in focal cerebral ischemia

Pil W. Huh, Ludmila Belayev, Weizhao Zhao, Sebastian Koch, Raul Busto, Myron Ginsberg

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Object. The purpose of this study was to compare the effects of prolonged hypothermia on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats. Methods. Male Sprague-Dawley rats were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion by retrograde insertion of an intraluminal nylon suture coated with poly-L-lysine through the external carotid artery into the internal carotid artery and the MCA. Two levels of prolonged postischemic cranial hypothermia (32°C and 27°C) and one level of intraischemic cranial hypothermia (32°C) were compared with the ischemic normothermia (37°C) condition. Target cranial temperatures were maintained for 3 hours and then gradually restored to 35°C over an additional 2-hour period. The animals were evaluated using a quantitative neurobehavioral battery of tests before inducing MCA occlusion, during occlusion (at 60 minutes postonset in all rats except those in the intraischemic hypothermia group), and at 24, 48, and 72 hours after reperfusion. The rat brains were perfusion fixed at 72 hours after ischemia, and infarct volumes and brain edema were determined. Both intraischemic and postischemic cooling to 32°C led to similar significant reductions in cortical infarct volume (by 89% and 88%, respectively) and total infarct volume (by 54% and 69%, respectively), whereas postischemic cooling to 27°C produced lesser reductions (64% and 49%, respectively), which were not statistically significant. All three hypothermic regimens significantly lessened hemispheric swelling and improved the neurological score at 24 hours. The authors' data confirm that a high degree of histological neuroprotection is conferred by postischemic cooling to 32°C, which is virtually equivalent to that observed with intraischemic cooling to the same level. Conclusions. These results may be relevant to the design of future clinical trials of therapeutic hypothermia for acute ischemic stroke.

Original languageEnglish
Pages (from-to)91-99
Number of pages9
JournalJournal of Neurosurgery
Volume92
Issue number1
StatePublished - Jan 1 2000

Fingerprint

Hypothermia
Brain Ischemia
Middle Cerebral Artery Infarction
External Carotid Artery
Induced Hypothermia
Nylons
Brain Edema
Middle Cerebral Artery
Internal Carotid Artery
Halothane
Sutures
Lysine
Reperfusion
Sprague Dawley Rats
Ischemia
Perfusion
Stroke
Clinical Trials
Temperature
Wounds and Injuries

Keywords

  • Brain temperature
  • Hypothermia
  • Middle cerebral artery occlusion
  • Neuroprotection
  • Rat
  • Stroke
  • Vascular occlusion

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Comparative neuroprotective efficacy of prolonged moderate intraischemic and postischemic hypothermia in focal cerebral ischemia. / Huh, Pil W.; Belayev, Ludmila; Zhao, Weizhao; Koch, Sebastian; Busto, Raul; Ginsberg, Myron.

In: Journal of Neurosurgery, Vol. 92, No. 1, 01.01.2000, p. 91-99.

Research output: Contribution to journalArticle

@article{4b0c8e00a8d84480aca9ccf745cfc3ae,
title = "Comparative neuroprotective efficacy of prolonged moderate intraischemic and postischemic hypothermia in focal cerebral ischemia",
abstract = "Object. The purpose of this study was to compare the effects of prolonged hypothermia on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats. Methods. Male Sprague-Dawley rats were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion by retrograde insertion of an intraluminal nylon suture coated with poly-L-lysine through the external carotid artery into the internal carotid artery and the MCA. Two levels of prolonged postischemic cranial hypothermia (32°C and 27°C) and one level of intraischemic cranial hypothermia (32°C) were compared with the ischemic normothermia (37°C) condition. Target cranial temperatures were maintained for 3 hours and then gradually restored to 35°C over an additional 2-hour period. The animals were evaluated using a quantitative neurobehavioral battery of tests before inducing MCA occlusion, during occlusion (at 60 minutes postonset in all rats except those in the intraischemic hypothermia group), and at 24, 48, and 72 hours after reperfusion. The rat brains were perfusion fixed at 72 hours after ischemia, and infarct volumes and brain edema were determined. Both intraischemic and postischemic cooling to 32°C led to similar significant reductions in cortical infarct volume (by 89{\%} and 88{\%}, respectively) and total infarct volume (by 54{\%} and 69{\%}, respectively), whereas postischemic cooling to 27°C produced lesser reductions (64{\%} and 49{\%}, respectively), which were not statistically significant. All three hypothermic regimens significantly lessened hemispheric swelling and improved the neurological score at 24 hours. The authors' data confirm that a high degree of histological neuroprotection is conferred by postischemic cooling to 32°C, which is virtually equivalent to that observed with intraischemic cooling to the same level. Conclusions. These results may be relevant to the design of future clinical trials of therapeutic hypothermia for acute ischemic stroke.",
keywords = "Brain temperature, Hypothermia, Middle cerebral artery occlusion, Neuroprotection, Rat, Stroke, Vascular occlusion",
author = "Huh, {Pil W.} and Ludmila Belayev and Weizhao Zhao and Sebastian Koch and Raul Busto and Myron Ginsberg",
year = "2000",
month = "1",
day = "1",
language = "English",
volume = "92",
pages = "91--99",
journal = "Journal of Neurosurgery",
issn = "0022-3085",
publisher = "American Association of Neurological Surgeons",
number = "1",

}

TY - JOUR

T1 - Comparative neuroprotective efficacy of prolonged moderate intraischemic and postischemic hypothermia in focal cerebral ischemia

AU - Huh, Pil W.

AU - Belayev, Ludmila

AU - Zhao, Weizhao

AU - Koch, Sebastian

AU - Busto, Raul

AU - Ginsberg, Myron

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Object. The purpose of this study was to compare the effects of prolonged hypothermia on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats. Methods. Male Sprague-Dawley rats were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion by retrograde insertion of an intraluminal nylon suture coated with poly-L-lysine through the external carotid artery into the internal carotid artery and the MCA. Two levels of prolonged postischemic cranial hypothermia (32°C and 27°C) and one level of intraischemic cranial hypothermia (32°C) were compared with the ischemic normothermia (37°C) condition. Target cranial temperatures were maintained for 3 hours and then gradually restored to 35°C over an additional 2-hour period. The animals were evaluated using a quantitative neurobehavioral battery of tests before inducing MCA occlusion, during occlusion (at 60 minutes postonset in all rats except those in the intraischemic hypothermia group), and at 24, 48, and 72 hours after reperfusion. The rat brains were perfusion fixed at 72 hours after ischemia, and infarct volumes and brain edema were determined. Both intraischemic and postischemic cooling to 32°C led to similar significant reductions in cortical infarct volume (by 89% and 88%, respectively) and total infarct volume (by 54% and 69%, respectively), whereas postischemic cooling to 27°C produced lesser reductions (64% and 49%, respectively), which were not statistically significant. All three hypothermic regimens significantly lessened hemispheric swelling and improved the neurological score at 24 hours. The authors' data confirm that a high degree of histological neuroprotection is conferred by postischemic cooling to 32°C, which is virtually equivalent to that observed with intraischemic cooling to the same level. Conclusions. These results may be relevant to the design of future clinical trials of therapeutic hypothermia for acute ischemic stroke.

AB - Object. The purpose of this study was to compare the effects of prolonged hypothermia on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats. Methods. Male Sprague-Dawley rats were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion by retrograde insertion of an intraluminal nylon suture coated with poly-L-lysine through the external carotid artery into the internal carotid artery and the MCA. Two levels of prolonged postischemic cranial hypothermia (32°C and 27°C) and one level of intraischemic cranial hypothermia (32°C) were compared with the ischemic normothermia (37°C) condition. Target cranial temperatures were maintained for 3 hours and then gradually restored to 35°C over an additional 2-hour period. The animals were evaluated using a quantitative neurobehavioral battery of tests before inducing MCA occlusion, during occlusion (at 60 minutes postonset in all rats except those in the intraischemic hypothermia group), and at 24, 48, and 72 hours after reperfusion. The rat brains were perfusion fixed at 72 hours after ischemia, and infarct volumes and brain edema were determined. Both intraischemic and postischemic cooling to 32°C led to similar significant reductions in cortical infarct volume (by 89% and 88%, respectively) and total infarct volume (by 54% and 69%, respectively), whereas postischemic cooling to 27°C produced lesser reductions (64% and 49%, respectively), which were not statistically significant. All three hypothermic regimens significantly lessened hemispheric swelling and improved the neurological score at 24 hours. The authors' data confirm that a high degree of histological neuroprotection is conferred by postischemic cooling to 32°C, which is virtually equivalent to that observed with intraischemic cooling to the same level. Conclusions. These results may be relevant to the design of future clinical trials of therapeutic hypothermia for acute ischemic stroke.

KW - Brain temperature

KW - Hypothermia

KW - Middle cerebral artery occlusion

KW - Neuroprotection

KW - Rat

KW - Stroke

KW - Vascular occlusion

UR - http://www.scopus.com/inward/record.url?scp=0033984056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033984056&partnerID=8YFLogxK

M3 - Article

VL - 92

SP - 91

EP - 99

JO - Journal of Neurosurgery

JF - Journal of Neurosurgery

SN - 0022-3085

IS - 1

ER -