血塞通注射液对沙土鼠脑缺血损伤的保护作用

通过夹闭沙土鼠双侧颈总动脉１０ ｍｉｎ 或２０ ｍｉｎ 后再灌７ ｄ 或１ ｄ , 造成脑缺血再灌模型, 检测血塞通对沙土鼠脑组织钙、水含量的影响, 以及对海马 Ｃ Ａ１ 区死亡的神经元迟发性损伤的保护作用． 结果显示, 血塞通可降低缺血后脑组织钙的含量, 减少海马 Ｃ Ａ１ 区死亡的神经元数量, 增加神经元密度． 实验结果提示血塞通对脑缺血再灌损伤有一定的保护作用．     

Characteristics of pentobarbital discrimination in the gerbil: Transfer and antagonism

Experiment 1. Gerbils were trained in a T-shaped maze to discriminate the effects produced by pentobarbital (P-barb. 15 mg/kg, i.p.) and the effects of saline. The response, a left or right turn in the maze, was thus contingent upon the prevailing training condition (P-barb. or saline). The criterion of performing 8 correct first trial choices in 10 consecutive sessions was reached within 20 training sessions. Tests with descending doses of P-barb. yielded an ED₅₀ of 9 mg/kg. Tests with phenobarbital (40 mg/kg) or diazepam (2 and 4 mg/kg) solely maintained the drug response. P-barb. discrimination was reversed by megimide (ED₅₀: 8.5–9.6 mg/kg) and metrazol (ED₅₀: 24.9–27.9 mg/kg). Thus megimide was approximately 3 times more effective than metrazol. Metrazol (40 and 80 mg/kg) also counteracted the phenobarbital and diazepam response. Picrotoxin (2.5 and 5 mg/kg) was less effective whereas caffeine (100 mg/kg) and piracetam (100–1000 mg/kg) did not upset P-barb. discrimination. Experiment 2. Naive gerbils had to discriminate mixtures of P-barb. (15 mg/kg) plus either 40 or 80 mg/kg of metrazol from saline already at the start of the discriminative training. The drug combinations produced discriminable effects since most gerbils reached the acquisition criterion (8/10), although more slowly than gerbils trained with P-barb. solely. Gerbils trained without a drug stimulus (saline vs. saline) never attained the criterion during 60 consecutive sessions. In conclusion, reversal of established discrimination (Expt. 1) does not necessarily mean that the same drug combination lacks discriminable effects as demonstrated in Experiment 2.     

联合应用巴曲酶和依达拉奉对沙土鼠缺血再灌注后神经元凋亡的影响

探讨联合应用巴曲酶和依达拉奉对沙土鼠缺血再灌注后海马CA1区神经元凋亡的影响。以阻断沙土鼠双侧颈总动脉5min造成前脑完全缺血再灌注模型,并将其随机分为假手术组、对照组、巴曲酶组、联合治疗组。在不同时间点分别腹腔注射生理盐水、巴曲酶、巴曲酶和依达拉奉后,用原位末端标记法染色以及电镜下观察沙土鼠海马CA1区凋亡细胞,并在光镜下计算海马CA1区的神经元凋亡率。联合使用巴曲酶和依达拉奉后海马CAl区细胞凋亡率明显减少,与对照组及巴曲酶组比较P<0.05;海马CAl区细胞凋亡率在巴曲酶组0～24h时间点之间比较P>0.05,在0～24h时间点与48～72h时间点比较P<0.05;海马CAl区细胞凋亡率在联合治疗组0～48h时间点之间比较P>0.05;在0～48h时间点与72h时间点比较P<0.05。电镜下显示对照组海马CA1区锥体细胞的线粒体肿胀,胞核固缩,核形态异常。巴曲酶组的海马锥体细胞病变较对照组轻。联合治疗组海马锥体细胞病变较巴曲酶组更轻。联合应用巴曲酶和依达拉奉较单独使用巴曲酶可明显减少脑缺血再灌注后神经元细胞的凋亡。而且在48h内仍有较好的脑保护作用。     

Protein-energy malnutrition impairs functional outcome in global ischemia

We investigated whether protein-energy malnutrition (PEM) exacerbates brain injury in global ischemia. It was hypothesized that PEM would increase secondary brain damage by worsening ischemia-induced depletion of glutathione (GSH) and increasing oxidative stress. Adult male gerbils were fed an adequate protein (12.5%; C) or low protein (2%; PEM) diet for 4 weeks and subjected to 5 min of bilateral carotid artery occlusion (Ischemia) or sham surgery (Sham). At 12 h post-ischemia, GSH and markers of oxidative stress were measured in hippocampus and neocortex. The remaining gerbils were tested in the open field on days 3, 7, and 10, with viable hippocampal CA1 neurons assessed on day 10. Although the habituation of C-Ischemia gerbils in the open field was normal by day 7, PEM-Ischemia gerbils failed to habituate even by day 10 and spent greater time in the outer zone (P < 0.05). Mean (+/-SEM) total number of viable CA1 neurons at 10 days post-ischemia were C-Sham = 713 (13), C-Ischemia = 264 (48), PEM-Sham = 716 (12), and PEM-Ischemia = 286 (66). Although PEM did not increase CA1 neuron loss caused by ischemia, a subset (4/12) of PEM-Ischemia gerbils showed dramatic reactive gliosis accompanied by extensive neuronal loss. Hippocampal protein thiols were decreased by PEM and ischemia. Although the mechanism is yet to be established, the finding that PEM worsens functional outcome following global ischemia is clinically relevant since 16% of elderly are nutritionally compromised at the time of admission for stroke.     

Time profile of calcium accumulation in hippocampus,striatum and frontoparietal cortex after transient forebrain ischemia in the gerbil

Summary The topical and temporal relationship between neuronal injury and calcium loading was investigated in gerbils following bilateral carotid artery occlusion for 5 or 10 min and recirculation times from 15 min to 7 days. The association of histochemically visible calcium deposits with neuronal death was assessed by combining two calcium stains, alizarin red and arsenazo III, with conventional histological techniques. Neuronal calcium accumulation was evaluated morphometrically in the striatum, the frontoparietal cortex and the CA1 and CA4 sectors of the hippocampus. After 5-min ischemia and 1–2 days of recirculation numerous calcium-containing neurons appeared in the CA4 sector but only a few were present in the CA1 sector. After 4 days of recirculation calcium accumulation was visible in the whole CA1 sector and the dorso-lateral part of striate nucleus. After 10-min ischemia calcium accumulation started in these regions, as well as in the cortex, already after 1 day. In the CA1 sector calcium accumulation followed a typical time course: on day 2 only the lateral parts were affected, while on day 4 the whole CA1 neuronal band was calcium positive. The regional distribution of histological lesions matched that of calcium loading and, furthermore, the lesions appeared after a corresponding delay in the respective regions. Morphometric evaluations of calcium staining and histological lesions in the CA1 sector revealed a high correlation, indicating that calcium accumulation and neuronal death are closely associated both topically and temporally. This suggests that disturbances of calcium homeostasis such as those measured by this histochemical technique are the consequence of and not the reason for ischemic cell death.     

Effects of alcohol and caffeine on wheel running activity in the Mongolian gerbil.

This study investigated the effects of various doses of alcohol (0.8, 1.6, 2.4 g/kg) and caffeine (5, 10, 15, 20 mg/kg) on wheel running activity in 180 male and female adult Mongolian gerbils. Animals were tested for two 10-min trials 48 hours apart. Thirty min prior to Trial 2, injections were administered intraperitoneally. The results indicate that low doses of both alcohol and caffeine increase and higher doses of alcohol decrease wheel running activity in gerbils of both sexes. These results agree with other findings on activity in other animals, and serve as a baseline for future drug research in the gerbil.     

Effects of chlormethiazole (Heminevrin®) on drug discrimination and open-field behavior in gerbils

Chlormethiazole (CMZ, 80 mg/kg) was used as a discriminative stimulus in gerbils; i.e., the presence or absence of certain effects of the drug controlled the choice behavior (left or right turn) of the animals trained to escape electric shocks in a T-maze. Substitution tests with pentobarbital (5–25 mg/kg) and ethanol (0.5–2.5 g/kg) indicated at least a partial similarity in the stimulus effects of CMZ and the two other drugs. The CMZ stimulus was attenuated by 30 mg/kg of the analeptic bemegride (BMG). In Experiment II, gerbils were trained to discriminate CMZ (80 mg/kg) from either of two doses of ethanol (1.5 or 2.0 g/kg). The acquisition rates for the latter groups appeared some-what slower than that noted for the gerbils in Experiment I, although only one measure significantly differentiated the groups. A qualitative difference is proposed as the basis for the discrimination between CMZ and ethanol. Open-field (O-F) tests 5 min after injections of CMZ (80 mg/kg) depressed both horizontal (ambulation) and vertical (rearing) activity, effects found to be counteracted by BMG (30 mg/kg) during the initial segment of the O-F testing. However, a second O-F test carried out 60 min after injections showed that the behaviors of the gerbils treated with the combination of CMZ and BMG were now markedly depressed. The effects of the drug combination on colonic temperature of the gerbils showed similar changes over time; i.e., the mixture of BMG and CMZ resulted in a normal colonic temperature response 5 min postinjection (p.i.), after which a marked drop of temperature followed at the recordings 60 min p.i.     

Circadian studies of the spontaneous rotational behavior of the gerbil

Normal unoperated gerbils rotate or turn in circles spontaneously (i.e., without lesions or drugs). Two experiments were conducted to determine possible circadian patterns of spontaneous rotation. In Experiment 1, one hour testing indicated that rotational behavior during the light and dark portions of the diurnal cycle are not different. In Experiment 2, continuous monitoring of rotation for 6-day sessions revealed that gerbils maintain a steady baseline level of rotation throughout the diurnal cycle, unlike rats which spontaneously rotate only at night. Two-thirds of gerbils tested rotated in one direction during an initial phase of testing and then switched the direction of preferred rotation for the remainder of the test session. These shifts in direction of rotation by some gerbils may reflect the influence of arousal on lateralized behavior. Thus, the spontaneous rotational behavior of gerbils is characterized both by a distinct lack of circadian fluctuation and directional variability.     

Delta9-tetrahydrocannabinol and pentobarbital as discriminative cues in the Mongolian Gerbil (Meriones unguiculatus)

Male Mongolian gerbils were trained to escape electric shocks in a T-shaped maze contingent upon the presence or absence of certain drug effects (state-dependency; StD). The drug discriminative cues used were those of either delta9-tetrahydrocannabinol (THC) or pentobarbital (P-barb.) vis-à-vis the respective vehicles. Several doses of THC (0.5-16.0 mg/kg) were used and compared with P-barb. (20.0 mg/kg), a dose at which the most rapid drug discrimination occurs in the rat. When drug discrimination was established dose-time- and transfer characteristics for the training drugs were studied. Possible potentiation and antagonism was also examined in the pentobarbital trained gerbils. It was found that none of the THC doses were discriminated as rapidly as that of P-barb. Decreasing the amounts of training drug administered or increasing the injection-test intervals resulted in a decline of the number of drug associated choices. There was a maximum of 40% drug choices between THC and P-barb at the transfer tests. Mixtures of the two compounds increased the number of drug choices in an additive or even more than additive manner. Amphetamine (4.0 mg/kg) did not interact with the P-barb. induced choice responding. The analeptic drug, bemegride was found effective in antagonizing the P-barb. cued choice behavior.