212 M
Similar parameters from an ROI within the cortex adja- cent to the area of KCl application were measured from
the KCl experiments.
2.10. Statistical analysis Standard statistical methods were used to analyze data.
Differences between groups and the various parameters was determined using one-way analysis of variance
ANOVA and ANOVA with repeated measures to detect overall significance, followed by a post hoc multiple
comparison procedure Scheffe’s. Correlation was de- termined by Pearson’s correlation coefficient, followed by
a linear regression. Statistical significance was determined at
the P
,0.05 level. All data are presented as mean
6S.E.M.
Fig. 2. Striatal temperature in ischemic and non-ischemic brain under normothermic and mildly hypothermic conditions. Under normothermic
3. Results
conditions, rectal d and ischemic striatal . temperatures were similar, whereas non-ischemic striatal temperature j was approximate-
3.1. Correlative experiments
ly 1 8C higher. Under mildly hypothermic conditions, rectal s and
ischemic striatal , temperatures were similar, whereas non-ischemic striatal temperature h was approximately 2
8C higher. Cooling began
We found strong correlations between rectal and brain
immediately after occlusion of the middle cerebral artery MCAO, and
temperature r 50.92, P,0.0001, with brain temperature
rewarming began immediately after reperfusion arrow.
somewhat higher than rectal. The relationship was not entirely linear, as we found that when rectal temperature
was 37 8C, brain temperature was 388C, whereas when
brain temperature under normothermic conditions i.e. rectal temperature was 30
8C, brain temperature was 338C non-ischemic brain was corrected to 38
8C, and ischemic Table 1. Furthermore, cortical and striatal brain tempera-
brain was corrected to 37 8C.
tures were similar. Under ischemic conditions, striatal temperature within the non-ischemic side followed patterns
3.2. Focal cerebral ischemia similar to those observed in non-ischemic animals. How-
ever, the ischemic striatal temperature was lower than the There were no differences among any of the physiologi-
non-ischemic striatum, and was no different from the rectal cal parameters except temperature between groups. For
temperature Fig. 2. Therefore, we found it possible to each temperature group, 22 DWI image sets 11 mildly
reliably predict brain temperature from rectal temperature hypothermic and 11 normothermic sets were available for
measurements in this model. analysis at 0.5 h post-ischemia intraischemic, 14 image
ADC was found to vary linearly and directly with sets seven mildly hypothermic and seven normothermic
temperature. A 1 8C change in brain temperature corres-
sets were available for analysis 2.5 h post-ischemia post- ponded to a 1.6 change in ADC. Our results are in close
reperfusion and 15 image sets seven mildly hypothermic agreement with others’ who measured the temperature
and eight normothermic sets were available for analysis at dependence of the ADC in water and brain [18,23] as well
24 h. For the PWI scans, only six image sets were as in a mathematical model [32]. Although these changes
available for analysis at the 24-h time point among are quite small in comparison to the ADC reduction
normothermic animals, otherwise the numbers are the observed with ischemia, we used this relationship to
same as for DWI. correct all measured ADCs to the ADC corresponding to a
Mild hypothermia inhibited DWI lesion growth early
Table 1
a
Correlation of brain and rectal temperature n 53
Target rectal temperature 8C
Rectal temperature 8C
Brain temperature 8C
39 39.2
60.33 40.2
60.34 37
37.0 60.2
38.0 60.18
35 35.2
60.1 37.1
60.08 33
32.8 60.05
34.9 60.12
30 30.4
60.16 32.9
60.08
a
r 50.92, P,0.0001.
M .A. Yenari et al. Brain Research 885 2000 208 –219
213
Fig. 3. MRI of transient focal cerebral ischemia under conditions of mild hypothermia coronal plane a and normothermia b. DWI and ADC images show that the ischemic lesion left side of image is reduced in size at all time points compared to normothermia. PWI delay maps show a large delay area
intra-ischemically left side of image which reverses upon reperfusion and remains normal by 24 h. T2W image does not become positive until 24 h.
214 M
after the onset of ischemia and up to 24 h later. DWI lesion hypo 5
61.6, normo 2163, P,0.001; and 24 h: hypo areas of the ipsilateral hemisphere were intraischemic:
8 62, normo 2864, P,0.01 Figs. 3 and 4a. Striatal
hypo 10 64, normo 1963.2, P50.07; post-reperfusion:
ADC recovery by 24 h was significantly improved among mildly hypothermic animals. ADC recovery, compared to
the contralateral non-ischemic striata was 104 66 among
mild hypothermics versus 77 66 ADC recovery among
normothermics P ,0.05 Fig. 4b. Areas of significant
bolus peak delays were no different between groups at any time point. Cerebral perfusion was equally delayed during
MCA occlusion, but returned to near normal in both groups shortly after reperfusion Figs. 3 and 4c.
3.3. KCl- and ischemia-induced SDs KCl application produced SD-like waves on DWI in
non-ischemic animals which corresponded to the DC potential changes data not shown. This correlation has
been previously been described in detail by our group [12,48,49] and others [17,31]. Therefore, DC potential
shifts were not measured for subsequent studies. Maximum ADC decreases were significantly lower with decreased
temperature. Mild hypothermia prolonged ADC decline and ADC recovery times from the initial depolarization
compared to normothermia Table 2 and Fig. 5.
Among normothermic animals, ischemia resulted in SD- like ADC changes within peri-infarct zones. Mild hypo-
thermia suppressed SD generation within cortex among two of three animals, and these animals also did not have
any MRI-detected cortical injury. The third mildly hypo- thermic animal had a cortical lesion seen on DWI, and
SD-like waves were observed in peri-infarct regions. ADC decline and recovery times within the cortical peri-infarct
zone were slowed in this mildly hypothermic animal compared to the normothermics. SDs were detected within
peri-infarct regions in the mildly hypothermic group with prolonged ADC decline and recovery Table 3. ADC
decline and recovery times were approximately three times longer among mildly hypothermic animals compared nor-
mothermic ones P
,0.05. Time to terminal ADC de- crease was twice as long in mildly hypothermic animals
compared to controls. Maximum ADC decreases were lower among the mildly hypothermic group even after
Fig. 4. Temperature-dependent, MRI-detected ischemic lesion changes.
correction for temperature.
a Mild hypothermia attenuates DWI lesion area. Significant reduction in DWI lesion area of the ipsilateral hemisphere among the hypothermic
group is observed upon reperfusion 2 h and at 24 h. Trends showing reduced lesion size compared to the normothermic group are noted
4. Discussion
