Posttraumatic hypothermia is neuroprotective in a model of traumatic brain injury complicated by a secondary hypoxic insult

Yoshitaro Matsushita, Helen Bramlett, Ofelia Alonso, W. Dalton Dietrich

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Objective: Human traumatic brain injury frequently results in secondary complications, including hypoxia. In previous studies, we have reported that posttraumatic hypothermia is neuroprotective and that secondary hypoxia exacerbates histopathologic outcome after fluid-percussion brain injury. The purpose of this study was to assess the therapeutic effects of mild (33°C) hypothermia after fluid-percussion injury combined with secondary hypoxia. In addition, the importance of the rewarming period on histopathologic outcome was investigated. Design: Prospective experimental study in rats. Setting: Experimental laboratory in a university teaching hospital. Intervention: Intubated, anesthetized rats underwent normothermic parasagittal fluid-percussion brain injury (1.8-2.1 atmospheres) followed by either 30 mins of normoxia (n = 6) or hypoxic (n = 6) gas levels and by 4 hrs of normothermia (37°C). In hypothermic rats, brain temperature was reduced immediately after the 30-min hypoxic insult and maintained for 4 hrs. After hypothermia, brain temperature was either rapidly (n = 6) or slowly (n = 5) increased to normothermic levels. Rats were killed 3 days after traumatic brain injury, and contusion volumes were quantitatively assessed. Measurements and Main Results: As previously shown, posttraumatic hypoxia significantly increased contusion volume compared with traumatic brain injury-normoxic animals (p < .02). Importantly, although posttraumatic hypothermia followed by rapid rewarming (15 mins) failed to decrease contusion volume, those animals undergoing a slow rewarming period (120 mins) demonstrated significantly (p < .03) reduced contusion volumes, compared with hypoxic normothermic rats. Conclusions: These data emphasize the beneficial effects of posttraumatic hypothermia in a traumatic brain injury model complicated by secondary hypoxia and stress the importance of the rewarming period in this therapeutic intervention.

Original languageEnglish
Pages (from-to)2060-2066
Number of pages7
JournalCritical Care Medicine
Volume29
Issue number11
StatePublished - Nov 26 2001

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Rewarming
Hypothermia
Percussion
Contusions
Brain Injuries
Temperature
Brain
Therapeutic Uses
Atmosphere
Teaching Hospitals
Research Design
Gases
Traumatic Brain Injury
Hypoxia
Prospective Studies
Wounds and Injuries
Therapeutics

Keywords

  • Histopathology
  • Hypothermia
  • Hypoxia
  • Rat
  • Traumatic brain injury

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Posttraumatic hypothermia is neuroprotective in a model of traumatic brain injury complicated by a secondary hypoxic insult. / Matsushita, Yoshitaro; Bramlett, Helen; Alonso, Ofelia; Dalton Dietrich, W.

In: Critical Care Medicine, Vol. 29, No. 11, 26.11.2001, p. 2060-2066.

Research output: Contribution to journalArticle

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AB - Objective: Human traumatic brain injury frequently results in secondary complications, including hypoxia. In previous studies, we have reported that posttraumatic hypothermia is neuroprotective and that secondary hypoxia exacerbates histopathologic outcome after fluid-percussion brain injury. The purpose of this study was to assess the therapeutic effects of mild (33°C) hypothermia after fluid-percussion injury combined with secondary hypoxia. In addition, the importance of the rewarming period on histopathologic outcome was investigated. Design: Prospective experimental study in rats. Setting: Experimental laboratory in a university teaching hospital. Intervention: Intubated, anesthetized rats underwent normothermic parasagittal fluid-percussion brain injury (1.8-2.1 atmospheres) followed by either 30 mins of normoxia (n = 6) or hypoxic (n = 6) gas levels and by 4 hrs of normothermia (37°C). In hypothermic rats, brain temperature was reduced immediately after the 30-min hypoxic insult and maintained for 4 hrs. After hypothermia, brain temperature was either rapidly (n = 6) or slowly (n = 5) increased to normothermic levels. Rats were killed 3 days after traumatic brain injury, and contusion volumes were quantitatively assessed. Measurements and Main Results: As previously shown, posttraumatic hypoxia significantly increased contusion volume compared with traumatic brain injury-normoxic animals (p < .02). Importantly, although posttraumatic hypothermia followed by rapid rewarming (15 mins) failed to decrease contusion volume, those animals undergoing a slow rewarming period (120 mins) demonstrated significantly (p < .03) reduced contusion volumes, compared with hypoxic normothermic rats. Conclusions: These data emphasize the beneficial effects of posttraumatic hypothermia in a traumatic brain injury model complicated by secondary hypoxia and stress the importance of the rewarming period in this therapeutic intervention.

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