PMID- 9756600
OWN - NLM
STAT- MEDLINE
DCOM- 19981030
LR  - 20190727
IS  - 0039-2499 (Print)
IS  - 0039-2499 (Linking)
VI  - 29
IP  - 10
DP  - 1998 Oct
TI  - Optimal depth and duration of mild hypothermia in a focal model of transient 
      cerebral ischemia: effects on neurologic outcome, infarct size, apoptosis, and 
      inflammation.
PG  - 2171-80
AB  - BACKGROUND AND PURPOSE: Mild hypothermia is possibly the single most effective 
      method of cerebroprotection developed to date. However, many questions regarding 
      mild hypothermia remain to be addressed before its potential implementation in 
      the treatment of human stroke. Here we report the results of 2 studies designed 
      to determine the optimal depth and duration of mild hypothermia in focal stroke 
      and its effects on infarct size, neurological outcome, programmed cell death, and 
      inflammation. METHODS: Rats underwent a 2-hour occlusion of the left middle 
      cerebral artery. In the first study (I) animals were kept (intraischemically) at 
      either 37 degreesC (n=8), 33 degreesC (n=8), or 30 degreesC (n=8). Study II 
      consisted of 4 groups: (1) controls (37 degreesC, n=10), (2) 30 minutes of 
      hypothermia started at ischemic onset (33 degreesC, n=9), (3)1 hour (33 degreesC, 
      n=8), and (4) 2 hours (33 degreesC, n=8). Brain temperature was measured by a 
      thermocouple probe placed in the contralateral cortex. After suture removal, all 
      animals were rewarmed and reperfused for 22 hours (I) or 70 hours (II). RESULTS: 
      Mild hypothermia to 33 degreesC or 30 degreesC was neuroprotective (17+/-7% and 
      27+/-6%, respectively) relative to controls (53+/-8%, P<0.02), but 33 degreesC 
      was better tolerated and recovery from anesthesia was faster. The neurological 
      score of hypothermic animals was significantly better than that of controls (I & 
      II) at both 24 and 72 hours postischemia except for the 30-minute group (II), 
      which showed no improvement. In Study II, 2 hours of hypothermia reduced injury 
      by 59%, 1 hour reduced injury by 84% whereas 30 minutes did not reduce injury. 
      Normalized for infarct size, 2 hours of mild hypothermia decreased neutrophil 
      accumulation by 57% whereas both 1 hour and 30 minutes had no effect. At 72 
      hours, 1 and 2 hours of mild hypothermia decreased transferase dUTP nick-end 
      labeling (TUNEL) staining by 78% and 99%, respectively, and 30 minutes of 
      hypothermia had no effect. CONCLUSIONS: Intraischemic mild hypothermia must be 
      maintained for 1 to 2 hours to obtain optimal neuroprotection against ischemic 
      cell death due to necrosis and apoptosis.
FAU - Maier, C M
AU  - Maier CM
AD  - Departments of Neurosurgery, Stanford Stroke Center, Stanford University, 
      Stanford, Calif.
FAU - Ahern, K v
AU  - Ahern Kv
FAU - Cheng, M L
AU  - Cheng ML
FAU - Lee, J E
AU  - Lee JE
FAU - Yenari, M A
AU  - Yenari MA
FAU - Steinberg, G K
AU  - Steinberg GK
LA  - eng
GR  - K08 NS01860/NS/NINDS NIH HHS/United States
GR  - MH10748/MH/NIMH NIH HHS/United States
GR  - R01 NS27292/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Cerebral Infarction/*pathology
MH  - DNA Fragmentation
MH  - Encephalitis/pathology
MH  - *Hypothermia, Induced
MH  - Ischemic Attack, Transient/genetics/*pathology/*physiopathology
MH  - Male
MH  - Nervous System/*physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Time Factors
EDAT- 1998/10/02 00:00
MHDA- 1998/10/02 00:01
CRDT- 1998/10/02 00:00
PHST- 1998/10/02 00:00 [pubmed]
PHST- 1998/10/02 00:01 [medline]
PHST- 1998/10/02 00:00 [entrez]
AID - 10.1161/01.str.29.10.2171 [doi]
PST - ppublish
SO  - Stroke. 1998 Oct;29(10):2171-80. doi: 10.1161/01.str.29.10.2171.