Postischemic spontaneous hyperthermia and its effects in middle cerebral artery occlusion in the rat

This study examined the time course and effects of postischemic spontaneous hyperthermia after transient and permanent focal ischemia. Rats underwent a 90-min, 120-min, or permanent middle cerebral artery occlusion (MCAO). Body temperatures started rising 15-20 min after MCAO and reached 39-40.5 degrees C during the first hour. Sustained hyperthermia was observed during the rest of the first 24 h. In another experiment, rats were subjected to the same interventions, but a normothermic body temperature was maintained. Spontaneous hyperthermia significantly increased the infarct volumes measured 48 h after MCAO in all groups. Reperfusion 2 h after the onset of ischemia was not beneficial in the hyperthermic animals in contrast to the normothermic group. We also examined the effect of spontaneous hyperthermia on the temporal progression of infarcted and penumbral areas 4, 12, or 48 h after MCAO. During spontaneous hyperthermia, penumbral areas became infarcted areas more rapidly, which was most expressed at 4 h. These findings demonstrate that severe spontaneous hyperthermia can occur in rats after MCAO and that it not only increases the infarct volumes in both transient and permanent ischemia, but also accelerates the incorporation of penumbral areas into necrotic areas, which significantly decreases the window of opportunity for therapeutic interventions.     

Immediate or delayed mild hypothermia prevents focal cerebral infarction

The protective effect of mild hypothermia was studied in rodent models of both permanent and transient focal cerebral ischemia. In Expt. 1, Wistar rats were exposed to 6 h permanent ischemia by bilateral occlusion of both common carotid arteries and right middle cerebral artery. In Expt. 2, animals were exposed to 3 h transient ischemia followed by 21 h reperfusion, and in Expt. 3, 3 h transient ischemia was followed by 69 h of reperfusion. Expt. 4 used 3 h transient ischemia followed by 3 h reperfusion. In Expt. 1, animals maintained at 37 degrees C rectal (normothermia) suffered a mean infarct volume (+/- S.D.) of 142 +/- 44 mm3 (n = 6), which was reduced for those exposed to permanent hypothermic (32 degrees C) ischemia to 56 +/- 64 mm3 (n = 10) (P less than 0.05). In Expt. 2, normothermic ischemia and reperfusion resulted in an infarction of 211 +/- 35 mm3 (n = 6). Intra-ischemic hypothermia (32 degrees C) followed by 21 h of normothermic reperfusion resulted in 17 +/- 12 mm3 of infarction (n = 9) (P less than 0.001). Hypothermia for either the first or second 1.5 h of the 3 h ischemic insult reduced the infarct volume to 116 +/- 76 mm3 (n = 6) (P less than 0.05) or 108 +/- 73 mm3 (n = 7) (P less than 0.01), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

病变侧亚低温对局部脑缺血再灌流损伤有关因素的影响

目的　研究病变侧脑亚低温对脑缺血再灌流损伤梗塞体积、 Ｎ Ｏ 的影响确定病变侧亚低温的疗效, 探讨机理。方法　应用可反馈控温半导体致冷块对大鼠局灶脑缺血模型病变侧降温至３２ ～３３ ℃研究持续缺血及再灌流损伤的保护作用及有关因素的影响。结果　持续缺血１０ 分钟低温组及缺血４０ 分钟再灌流并低温组梗塞体积均小于常温对照组。亚低温组 Ｎ Ｏ 含量明显低于常温对照组。结论　病变侧亚低温对脑缺血再灌流损伤在一定时间窗内有明显保护作用, 而亚低温使 Ｎ Ｏ 产生减少可能是其脑保护作用的部分机制。     

Mild hypothermia enhances the neuroprotective effects of FK506 and expands its therapeutic window following transient focal ischemia in rats

FK506 (tacrolimus), an immunosuppressant, reportedly reduces ischemic brain injury following transient middle cerebral artery occlusion (MCAO) in rats. The authors previously reported that the therapeutic window of FK506 in this model is more than 1 h, but less than 2 h. The aim of the present study is to determine whether mild hypothermia (35 degrees C) enhances the neuroprotective effects of FK506 and expands its therapeutic window. Sprague-Dawley rats were subjected to 2 h MCAO followed by 24 h reperfusion. Animals were randomly divided into four groups: (I) vehicle-treated normothermic group; (II) FK506-treated normothermic group; (III) vehicle-treated hypothermic group; (IV) FK506-treated hypothermic group. Animals received a single injection of FK506 (0.3 mg/kg) or vehicle intravenously at 2 h after ischemic induction. During ischemia, temporal muscle and rectal temperatures were maintained at 37 degrees C in the normothermic animals and at 35 degrees C in the hypothermic animals. Infarct volumes and neurological performance were evaluated at 24 h after reperfusion. The combination of FK506 and mild hypothermia significantly reduced infarct volume (cortex, -61%; striatum, -31%) and edema volume (cortex, -57%; striatum, -41%), while mild hypothermia or FK506 alone failed to improve ischemic brain damage. Furthermore, this combination also provided for the best functional outcome. These results demonstrate that the combination of FK506 and mild hypothermia significantly reduces ischemic brain damage following transient MCAO in rats, and expands the therapeutic window for FK506. This therapy may be a new approach for treatment of acute stroke.     

Neuroprotection in ischemic stroke--combination drug therapy and mild hypothermia in a rat model of permanent focal cerebral ischemia

We have recently demonstrated marked neuroprotective efficacy of a combination therapy with magnesium (calcium- and glutamate-antagonist), tirilazad (antioxidant) and mild hypothermia (MTH) in a rat model of transient focal cerebral ischemia. In the present study, we investigated MTH under conditions of permanent focal cerebral ischemia. In part I, 20 Sprague-Dawley rats were subjected to 6 h of permanent, laser-Doppler flowmetry (LDF) controlled middle cerebral artery occlusion (MCAO). Drugs were administered 30 min before and 1 h after MCAO. Hypothermia (33 degrees C) was maintained for 2 h. Infarct size was planimetrically determined after 6 h. In part II, 29 rats were assigned to the same treatment arms and subjected to 7 days of permanent MCAO. Neurological deficits and body weight were assessed daily. Infarct size was determined on day 7. In part I, MTH significantly reduced infarct formation by 52% after 6 h. In part II, high mortality within the first 3 days was observed in both groups. Treated animals showed a significantly better postoperative weight gain on day 7 and neurological recovery on days 6 and 7 compared to controls without significant differences in infarct volume. MTH seems to exert its neuroprotective properties even in a setting of permanent cerebral ischemia. High mortality and absence of infarct reduction after 7 days might be due to model limitations. Neurological recovery, the most important clinical outcome parameter, is significantly improved in 7-day survivors. Significant neuroprotection under conditions of permanent ischemia and former promising results in transient ischemia justify further investigations of MTH.     

不同低温对鼠永久性大脑中动脉阻塞后NF-κB表达及脑梗死体积的影响

目的:观察不同低温对大鼠永久性大脑中动脉阻塞后NF-κB表达及梗死体积的影响。方法:120只雄性SD大鼠随机分为三组:常温组(37℃),轻度低温组(34℃),中度低温组(32℃),每组分缺血2,4,6,12小时共四个亚组。采用栓线法制作永久性大脑中动脉阻塞(MCAO)模型,各组大鼠分别于缺血2,4,6,12小时后置于常温操作台和冰毯机上,分别保持肛温为37±0．5℃,34±0．5℃和32±0．5℃12小时。在各自规定时间点处死大鼠,其中三只作TTC染色,剩余作免疫组织化学染色。结果:与常温组相比,在缺血的各个时间点,除轻度低温组缺血6h外,两低温组的脑梗死体积均显著减小(P<0．05或P<0．01)。随缺血时间的延续,常温组NF-κB蛋白表达逐渐升高,在缺血6小时达高峰,并持续升高:除轻度低温组缺血4h外,在其余各时间点,两低温组的NF-κB蛋白水平较常温组显著下降(P<0．01),且低温治疗使NF-κB蛋白表达高峰前移。结论:低温治疗组与常温组比较,脑梗死体积显著减小(P<0．05或P<0．01);低温治疗还显著抑制NF-κB的蛋白表达(P<0．01),使NF-κB蛋白表达高峰前移。低温的脑保护作用可能与抑制NF-κB的表达有关。     

Mild hypothermia reduces infarct size resulting from temporary but not permanent focal ischemia in rats.

BACKGROUND AND PURPOSE: Mild hypothermia (32-35 degrees C) has been repeatedly shown in laboratory models to reduce damage resulting from global cerebral ischemic insults. Little information is available, however, regarding the protective potential of mild hypothermia against focal ischemia. We designed the present study to determine whether mild hypothermia influences outcome from either temporary or permanent middle cerebral artery occlusion in the rat. METHODS: In experiment 1 (permanent occlusion), mechanically ventilated, halothane-anesthetized spontaneously hypertensive rats underwent permanent ligation of the middle cerebral artery. Pericranial temperature was maintained at either 37 degrees C (n = 11) or 33 degrees C (n = 11) during the first 2 hours of occlusion. In experiment 2 (temporary occlusion), the vessel was occluded for 1 hour only. Pericranial temperature was controlled at either 37 degrees C (n = 12) or 33 degrees C (n = 14) during ischemia and for 1 hour after reperfusion. In both experiments, the rats were allowed to recover, with neurological function scored at 24 and 96 hours after onset of ischemia. Cerebral infarct volume (as determined by nitro blue tetrazolium staining) was planimetrically evaluated 96 hours after onset of ischemia. RESULTS: No difference in infarct volume was observed between groups undergoing permanent occlusion (177 +/- 53 mm3 for 37 degrees C rats, 167 +/- 71 mm3 for 33 degrees C rats [mean +/- SD]). Although neurologic function correlated with infarct volume at 96 hours (all animals in experiment 1 combined; p less than 0.01), we were unable to demonstrate an intergroup difference in function. In animals undergoing temporary occlusion, mean +/- SD infarct volume was 48% less in the hypothermic group (89 +/- 54 mm3 for 37 degrees C, 46 +/- 31 mm3 for 33 degrees C; p less than 0.03). Neurological function again correlated with infarct size (p less than 0.02), but improvement in function approached significance for the hypothermic group (p less than 0.06) at 24 hours after reperfusion only. CONCLUSIONS: Benefits from mild hypothermia may be obtained under conditions of temporary but not permanent middle cerebral artery occlusion in the rat.     

The effect of hypothermia on transient middle cerebral artery occlusion in the rat.

We investigated the effect of moderate whole body hypothermia (30 degrees C) on transient middle cerebral artery occlusion (MCAO) in the rat. Male Wistar rats were subjected to 2 h of ischemia by inserting a suture into the lumen of the internal carotid artery and occluding the origin of the MCA. Experimental groups were (a) MCAO induced at 37 degrees C body temperature (n = 15); (b) 30 degrees C body temperature induced prior to ischemia and maintained for 2 h of MCAO and 1 h of reperfusion (n = 12); and (c) MCAO with regional brain and body temperatures measured in normothermic (n = 3) and hypothermic MCAO rats (n = 2). Histopathological evaluation was performed 96 h after reperfusion. All normothermic MCAO animals exhibited ischemic infarct involving the ipsilateral cortex and basal ganglia with infiltration of neutrophils, macrophages, and microvascular proliferation. Hypothermic MCAO animals exhibited minor ischemic damage ranging from selective neuronal injury to small focal areas of infarct with minimal inflammatory response. Our data demonstrate that transient ischemia induced by using the intra-arterial suture method to occlude the MCA results in a reproducible brain lesion and that moderate hypothermia has a profound protective effect on the brain injury after transient MCAO.     

Oxygen therapy in permanent brain ischemia: potential and limitations

BACKGROUND: Both normobaric (NBO) and hyperbaric (HBO) oxygen therapy are protective in transient cerebral ischemia. In contrast, in permanent ischemia models, which reflect the majority of clinical strokes, the effectiveness of NBO is unknown, and the effectiveness of HBO is controversial. The goals of the present study were to compare both oxygen therapies in 2 models of permanent ischemia, to study the effect of time window, and to evaluate the combination of both oxygen therapies. METHODS: Distal or proximal permanent occlusion of middle cerebral artery (MCAO) was induced by coagulation or filament, respectively. Mice received air, NBO, a single or repeated HBO (3 ata) treatments. Infarct sizes were quantified at 7 days (coagulation) and 24 h (filament), respectively. RESULTS: Following MCA coagulation, infarct volume was 12.9+/-1.6 mm3 in mice breathing air. When started 45 min or 120 min after MCAO, NBO (10.8+/-2.2) and significantly more potently HBO (7.8+/-0.9) reduced infarct size. Repeated HBO treatments had no additional effect (8.3+/-2.3). HBO also significantly decreased TUNEL cell staining at 24 h. Combination of 60 min NBO plus 60 min HBO resulted in smaller cortical infarcts (8.7+/-1.5) than 120 min NBO alone (11.1+/-3.2). In contrast, infarct volumes in filament-induced permanent MCAO did not differ among rodents receiving air (50+/-24 mm3), NBO (48+/-16), or HBO (46+/-21). After filament-induced transient MCAO, however, HBO reduced infarct volume significantly. CONCLUSIONS: NBO and more effectively HBO protect the brain against permanent cortical ischemia. In extensive focal ischemia, however, oxygen therapy is only effective in case of early recanalization.     

Effects of RSR13, a synthetic allosteric modifier of hemoglobin, alone and in combination with dizocilpine, on outcome from transient focal cerebral ischemia in the rat

This study examined the effect of a pharmacologically induced rightward shift in the partial pressure of oxygen at which 50% of hemoglobin is saturated (P50) on outcome from transient focal cerebral ischemia in the rat. Halothane anesthetized rats (n=20 per group) were given saline or a single 15-min infusion of 150 mg/kg RSR13 (2-[4-[[3,5-dimethylanilino) carbonyl]methyl]phenoxy]-2-methylproprionic acid) intravenously before or 30 min after onset of 75 min of middle cerebral artery filament occlusion (MCAO). Seven days later, severity of hemiparesis and cerebral infarct size were examined. RSR13 alone did not significantly improve outcome. Conscious normothermic rats (n=12 per group) were also given RSR13 (150 mg/kg) or 0.9% NaCl intravenously and subjected to 75 min of MCAO with 7 days of recovery. Again, RSR13 alone did not significantly reduce infarct size or improve neurologic score. A dose-response curve for dizocilpine (MK-801) was then constructed in conscious normothermic rats subjected to 75 min of MCAO. Dizocilpine (0.5 mg/kg i.v.) caused a 90% reduction in mean infarct size while 0.25 mg/kg reduced infarct size by 48%. Other rats were then subjected to 75 min of MCAO after being given dizocilpine (0.25 mg/kg i.v.; n=18) or RSR13 (150 mg/kg i.v. )+dizocilpine (0.25 mg/kg i.v.; n=15). RSR13+dizocilpine resulted in smaller cortical infarct volume (8+/-14 mm3 vs. 34+/-37 mm3, p<0.02) and total cerebral infarct volume (46+/-28 mm3 vs. 81+/-60 mm3, p<0. 05) compared to dizocilpine alone, respectively. We conclude that a pre-ischemic peak increase in P50 of approximately 25 mmHg alone is insufficient to reduce focal ischemic injury, but may be advantageous when used in conjunction with other neuroprotective agents.     

NXY-059, a novel free radical trapping compound, reduces cortical infarction after permanent focal cerebral ischemia in the rat

Free radicals have gained wide acceptance as mediators of cerebral ischemic injury. It has previously been reported that a spin trap nitrone, alpha-phenyl-N-tert-butyl nitrone (PBN), can reduce infarct volumes in rats subjected to either permanent or transient focal cerebral ischemia. A recent study has demonstrated that NXY-059, a novel free radical trapping nitrone compound, has a neuroprotective effect against transient focal cerebral ischemia. This study was designed to determine the effect of NXY-059 in a rodent model of permanent focal cerebral ischemia. Male spontaneously hypertensive rats were subjected to permanent middle cerebral artery occlusion (MCAO) by placement of a microaneurysm clip on the middle cerebral artery (MCA). Animals were divided into three groups: (1) physiological saline given as a 1 ml/kg i.v. bolus administered 5 min post MCAO followed immediately by a continuous i.v. infusion of 0.5 ml/h of physiological saline for 24 h (n=10); (2) 30 mg/kg, 1 ml/kg, i.v. bolus of NXY-059 dissolved in physiological saline administered 5 min post MCAO followed immediately by a continuous i.v. infusion of 30 mg/kg/h, 0.5 ml/h, of NXY-059 for 24 h (n=9); (3) 60 mg/kg, 1 ml/kg, i.v. bolus of NXY-059 dissolved in physiological saline administered 5 min post MCAO followed immediately by a continuous i.v. infusion of 60 mg/kg/h, 0.5 ml/h, of NXY-059 for 24 h (n=12). Infarction was quantified after a survival period of 24 h. Differences in infarct volume were examined with one-way ANOVA following Dunnet's multiple comparison test. The percentage of cortical infarction in the saline control group was 22.6 +/- 6.8% (mean+/-S.D.) of contra-lateral hemisphere, and in the 30 mg/kg/h NXY-059-treated group was 17.4% +/- 6.8% (NS). Plasma concentration (microM/l) of NXY-059 in the 30 mg/kg/h group was 80.2 +/- 52.2 (n=9), while in the 60 mg/kg/h group plasma concentration (microM/l) of NXY-059 was 391.0 +/- 207.0 (n=10). Infarction in the 60 mg/kg/h NXY-059-treated group was significantly reduced (P=0.009) to 14.5 +/- 5%. Our preliminary data demonstrate that administration of NXY-059 (60 mg/kg/h for 24 h) ameliorates cortical infarction in rats subjected to permanent focal cerebral ischemia with 24 h survival.     

Effects of mild whole body hyperthermia on graded focal ischaemia-reperfusion in a rat stroke model

The influence of body temperature on focal cerebral ischaemia-reperfusion was investigated by using a well established rat stroke model. Three different degrees of ischaemia were created in the cerebral cortex of the right middle cerebral artery territory by varying the duration of clamping of the bilateral common carotid arteries and the right middle cerebral artery with full reperfusion. Mild hyperthermic (body temperature 38-39 degrees C) influence during ischaemia significantly enhanced the severity of infarction in mild (30 min) ischaemia, mean infarct volume was 78% greater than normothermic (body temperature 36.5-37.5 degrees C) group (P < 0.001); and in moderate (60 min) ischaemia, mean infarct volume was 23% greater than in the normothermic group (P < 0.05); but no difference between the two groups was observed in severe (90 min) ischaemia. Our data suggest that mild whole body hyperthermia during focal ischaemia-reperfusion has a detrimental effect on the infarct volume only in mild and moderate ischaemia in this model.     

Hypothermia and brain-derived neurotrophic factor reduce glutamate synergistically in acute stroke

Moderate hypothermia and application of brain-derived neurotrophic factor (BDNF) have separately been identified as neuroprotective strategies in experimental cerebral ischemia. To assess their separate and combined effects on striatal glutamate release in the hyperacute phase of stroke, we inserted microdialysis probes into the striatum of rats 2 h before permanent middle cerebral artery occlusion (MCAO). The animals (N = 28) were randomly assigned to one of four treatment strategies commencing 30 min after MCAO: (1) hypothermia at 33 degrees C (n = 7); (2) intravenous BDNF infusion [300 microg/(kg/h) for 2 h, n = 7]; (3) combination of hypothermia and BDNF (n = 7); (4) control group (saline, n = 7). Infarct size at 5 h after MCAO was assessed with the silver-staining method. Total infarct volume was significantly reduced in the hypothermia (202.7 +/- 3.5 mm(3), P = 0.0002) and BDNF group (206.5 +/- 6.9 mm(3), P = 0.0006) as compared to control group (254.4 +/- 9.3 mm(3)). In the combination group, infarct size was further reduced with overall significance in post hoc tests (157.3 +/- 6.2 mm(3), P < 0.0001). Postischemic glutamate concentrations in the control group constantly remained significantly higher than in all other treatment groups. At 255 and 270 min after MCAO, striatal glutamate in the combination group decreased significantly more than in animals treated with hypothermia or BDNF alone.Combining hypothermia and BDNF therapy in the acute stage of ischemia has a synergistic effect in attenuating striatal glutamate release and reducing early infarct size.     

Spontaneous cerebral hypothermia diminishes focal infarction in rat brain.

BACKGROUND AND PURPOSE: Brain temperature during ischemia is known to strongly influence the extent of cellular injury. The objectives of the present study were to determine the effect of severe focal ischemia on brain temperature and to assess the influence of those changes on focal infarction. METHODS: Severe focal ischemia was produced in rats using permanent occlusion of the distal middle cerebral artery combined with transient (60-minute) bilateral carotid artery occlusion. The temperature of the ischemic focus was measured with a small subdural probe. Three groups of rats were studied. In the first group, brain temperature was permitted to decline spontaneously to 32 degrees C after occlusion. In the second, brain temperature was maintained at 37.5 degrees C during occlusion. In the third group, the brain temperature was maintained at 37.5 degrees C for 40 minutes postocclusion before cooling. After recovery for 24 hours, the volume of infarction was measured in histological sections. RESULTS: In the absence of cranial heating, the brain temperature fell to 33 degrees C by 10 minutes postocclusion, and infarct volume was 19 +/- 9 mm3 (mean +/- SEM; n = 6). Maintaining brain temperature at 37.5 degrees C increased the volume of infarction to 82 +/- 16 mm3 (n = 7; p < 0.001). Delayed cooling did not prevent the increase in infarct volume (75 +/- 16 mm3; n = 6). CONCLUSIONS: These results demonstrate that in the present model of transient focal ischemia, spontaneous cooling of the brain during ischemia diminishes the extent of focal infarction, relative to that observed when cerebral hypothermia is prevented or delayed for 40 minutes.     

Characterizing the diffusion/perfusion mismatch in experimental focal cerebral ischemia

Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) can rapidly detect lesions in acute ischemic stroke patients. The PWI volume is typically substantially larger than the DWI volume shortly after onset, that is, a diffusion/ perfusion mismatch. The aims of this study were to follow the evolution of the diffusion/ perfusion mismatch in permanent and 60- minute temporary focal experimental ischemia models in Sprague-Dawley rats using the intraluminal middle cerebral artery occlusion (MCAO) method. DWI and arterial spin-labeled PWI were performed at 30, 60, 90, 120, and 180 minutes after occlusion and lesion volumes (mm(3)) calculated At 24 hours after MCAO, and infarct volume was determined using triphenyltetrazolium chloride staining. In the permanent MCAO group, the lesion volume on the ADC maps was significantly smaller than that on the cerebral blood flow maps through the first 60 minutes after MCAO; but not after 90 minutes of occlusion. With 60 minutes of transient ischemia, the diffusion/perfusion mismatch was similar, but after reperfusion, the lesion volumes on ADC and cerebral blood flow maps became much smaller. There was a significant difference in 24- hour infarct volumes between the permanent and temporary occlusion groups.     

Dietary phytoestrogens improve stroke outcome after transient focal cerebral ischemia in rats

As phytoestrogens are postulated as being neuroprotectants, we assessed the hypothesis that dietary isoflavone-type phytoestrogens are neuroprotective against ischemic stroke. Transient focal cerebral ischemia (90 min) was induced by middle cerebral artery occlusion (MCAO) following the intraluminal thread technique, both in rats fed with soy-based diet and in rats fed with isoflavone-free diet. Cerebro-cortical laser-Doppler flow (cortical perfusion, CP), arterial blood pressure, core temperature, PaO2, PaCO2, pH and glycemia were measured before, during and after MCAO. Neurological examination and infarct volume measurements were carried out 3 days after the ischemic insult. Dietary isoflavones (both glycosides and aglycones) were measured by high-performance liquid chromatography. Neither pre-ischemic, intra-ischemic nor post-ischemic CP values were significantly different between the soy-based diet and the isoflavone-free diet groups. Animals fed with the soy-based diet showed an infarct volume of 122 +/- 20.2 mm3 (19 +/- 3.3% of the whole ipsilateral hemisphere volume). In animals fed with the isoflavone-free diet the mean infarct volume was significantly higher, 191 +/- 26.7 mm3 (28 +/- 4.1%, P < 0.05). Neurological examination revealed significantly higher impairment in the isoflavone-free diet group compared with the soy-based diet group (3.3 +/- 0.5 vs. 1.9 +/- 0.5, P < 0.05). These results demonstrate that dietary isoflavones improve stroke outcome after transient focal cerebral ischemia in such a way that a higher dietary isoflavone content results in a lower infarct volume and a better neurological status.     

Application of endovascular suture occlusion of middle cerebral artery in gerbils to obtain consistent infarction.

Middle cerebral artery occlusion (MCAO) by endovascular suture has gained increasing acceptance because it is relatively non-invasive and allows reperfusion. However, its application in rats has resulted in inconsistent infarction volumes which involve only the subcortex or subcortex plus some cortex. In order to eliminate this drawback, we applied the intraluminal suture occlusion of MCA to gerbils that have an incomplete Circle of Willis. MCAO was induced by inserting an endovascular 5-0 nylon suture with a blunted tip into the Circle of Willis. Animals were divided into two groups: permanent MCAO for 24 h (n = 8) and transient MCAO for 3 h with 21 h reperfusion (n = 8). The corrected infarction volume in the permanent MCAO group was 232 +/- 37 mm3 whereas it was 230 +/- 45 mm3 in the transient MCAO group. All animals in both groups had infarction in both cortex and subcortex. Results of this study show that endovascular suture occlusion of MCA can be easily applied in gerbils to obtain consistent infarction. This would allow both transient and permanent focal ischemia to be tested in the same model of ischemia.     

升压联合亚低温治疗对局灶性脑缺血再灌注的脑保护作用

目的　观察升压联合亚低温治疗对大鼠局灶性脑缺血再灌注的脑保护作用。方法　 32只大鼠随机分为对照组、升压组、亚低温组、升压 亚低温组 ,采用大鼠局灶性脑缺血再灌注模型 ,观察各组神经功能缺损评分和脑梗死体积。结果　升压组、亚低温组及升压 亚低温组神经功能缺损评分 (P <0 .0 5 )、脑梗死体积 (P <0 .0 1)均明显低于对照组 ;升压 亚低温组脑梗死体积明显低于升压组和亚低温组 (P <0 .0 5 )。结论　升压、亚低温对局灶性脑缺血再灌注损伤有明显脑保护作用 ,升压联合亚低温应用效果更佳     

Cerebral blood flow does not mediate the effect of brain temperature on recovery of extracellular potassium ion activity after transient focal ischemia in the rat

Temperature plays an important role in determining outcome following both global and focal brain ischemia. After focal ischemia, the degree of infarction decreases with mild hypothermia and increases with mild hyperthermia. In this study, brain extracellular potassium ion activity and local cerebral blood flow were measured in cerebral cortex during 60 min of middle cerebral artery occlusion and 60 min of re-perfusion. Brain temperature was maintained at 32-34 degrees C (mild hypothermia), 35.5-36.5 degrees C (normothermia), or 37.5-38.5 degrees C (mild hyperthermia) throughout ischemia and re-perfusion. In normothermic animals and to a greater degree in hyperthermic animals, extracellular potassium ion activity showed delayed secondary elevation above pre-ischemia values within 40-60 min after re-perfusion. No secondary elevation of extracellular potassium ion activity was observed in hypothermic animals. There was no difference in cortical blood flow among groups with varying brain temperature, indicating that delayed deterioration of brain potassium ion homeostasis was not caused by temperature dependent alteration of cerebral blood flow. The data suggest that loss of potassium ion homeostasis during re-perfusion after focal cerebral ischemia is caused by cellular rather than vascular dysfunction and may reflect secondary inhibition of energy metabolism.     

The significance of hypothermic acid-base management induced before ischemia in a rat model of transient middle cerebral artery occlusion

We investigated the effects of acid-base management during pre- and intra-ischemic hypothermia on regional cerebral blood flow (rCBF) and infarct volume using a transient focal cerebral ischemia model. Normal temperature was maintained in a group of 7 anesthetized rats, and hypothermia (30 degrees C) was maintained in two other groups of 7 anesthetized rats, in which alpha-stat (PaCO2 measured at 37 degrees C was maintained at 36 mmHg) and pH-stat (PaCO2 corrected for body temperature was maintained at 36 mmHg) conditions, respectively, were established. rCBF was monitored by laser-Doppler flowmetry in the ischemic penumbra. The middle cerebral artery (MCA) was occluded for 2 h and then reperfused. Infarct volume was measured after 24 h and expressed as a percentage of hemisphere volume. Pre-ischemic hypothermia reduced rCBF in the alpha-stat group and the pH-stat group to 52 +/- 2% and 86 +/- 7%, respectively (p < 0.01). After MCA occlusion, rCBF dropped in the control group, alpha-stat group, and pH-stat group to 57 +/- 11%, 31 +/- 9%, 27 +/- 10%, respectively. Infarct volume in the alpha-stat group, and pH-stat group was significantly smaller (10 +/- 1% and 7 +/- 2%) than in the control group (42 +/- 7%, p < 0.01), but no differences were found between the hypothermic groups. Differences in acid-base management in the present study did not affect infarct volume, but pre-ischemic rCBF in the alpha-stat group was significantly lower than in the pH-stat group. The steeper fall in rCBF after MCA occlusion in the pH-stat group suggested that the autoregulatory response of the collateral pathways may have been reduced in this group.