DNA brain damage after stress in rats

Objective

The purpose of this study was to verify the presence of DNA brain lesion after acute stress in rats.

Method

Adult male Wistar rats were divided into 3 groups according to the stressor (control, forced swimming or restraint), and sampled at 2 time points: immediately or 1 week after stress. Trunk blood and the brain areas (prefrontal cortex, amygdala and hippocampus) were extracted for DNA analysis by the comet assay. The cells were classified according to the damage index and damage frequency based on the comet tail size.

Results

Immediately after the stress, DNA damage was detected in the amygdala area and in the hippocampus after restraint and forced swimming. In the prefrontal cortex, DNA was damaged after forced swimming. However, no alteration was seen in blood. Seven days after the stress, DNA damage was still identified in the hippocampus after forced swimming and restraint, whereas no alteration was detected in the other brain areas or in blood.

Conclusion

One week after a single stressful event, a reversible DNA damage was identified in the prefrontal cortex and in the amygdala, whereas DNA damage in the hippocampus still remained.     

Methamphetamine neurotoxicity increases brain expression and alters behavioral functions of CB1 cannabinoid receptors

Cannabis is the most common secondary illicit substance in methamphetamine (METH) users, yet the outcomes of the concurrent consumption of both substances remain elusive. Capitalizing on recent findings on the implication of CB₁ cannabinoid receptors in the behavioral effects of METH, we hypothesized that METH-induced neurotoxicity may alter the brain expression of CB₁, thereby affecting its role in behavioral functions. To test this possibility, we subjected rats to a well-characterized model of METH neurotoxicity (4 mg/kg, subcutaneous × 4 injections, 2 h apart), and analyzed their CB₁ receptor brain expression three weeks later. METH exposure resulted in significant enhancements of CB₁ receptor expression across several brain regions, including prefrontal cortex, caudate-putamen, basolateral amygdala, CA1 hippocampal region and perirhinal cortex. In parallel, a different group of METH-exposed rats was used to explore the responsiveness to the potent cannabinoid agonist WIN 55,212-2 (WIN) (0.5-1 mg/kg, intraperitoneal), within several paradigms for the assessment of emotional and cognitive functions, such as open field, object exploration and recognition, and startle reflex. WIN induced anxiolytic-like effects in METH-exposed rats and anxiogenic-like effects in saline-treated controls. Furthermore, METH-exposed animals exhibited a significantly lower impact of WIN on the attenuation of exploratory behaviors and short-term (90 min) recognition memory. Conversely, METH neurotoxicity did not significantly affect WIN-induced reductions in locomotor activity, exploration time and acoustic startle. These results suggest that METH neurotoxicity may alter the vulnerability to select behavioral effects of cannabis, by inducing distinct regional variations in the expression of CB₁ receptors.     

Acute treatment with the organochalcogen 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one produces behavioral changes and inhibition of creatine kinase activity in the brain of rats

Organotellurium compounds have been synthesized since 1840, but their pharmacological and toxicological properties are still incipient. Therefore, the objective of this study was to verify the effect of acute administration with the organochalcogen 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on the activity of brain creatine kinase (CK), a key enzyme in energy metabolism, and on behaviors in the open field test of 30-day-old rats. Animals were treated intraperitoneally with a single dose of the organotellurium (125, 250, or 500 μg/kg body weight) and after 55 min of the drug administration the open field test was carried out. Behavior analyses were performed during 5 min and the number of the squares crossed, number of rearing, number of groomings and number of fecal boli were recorded by an observer. Then, the animals were sacrificed and the cerebral cortex, the hippocampus, and the cerebellum were dissected, and CK activity and sulfhydryl content were measured in the brain. The organotellurium increased the ambulation and rearing behaviors in the open field test at doses of 250 and 500 μg/kg. Moreover, the compound inhibited CK activity and provoked a reduced of thiol content measured by the sulfhydryl assay in all the tissues studied. Therefore, changes in energy homeostasis and motor behavior in rats treated with this organotellurium support the hypotheses that the brain is a potential target to pharmacological and toxicological effects of this compound.     

Different effects of chronic exposure to ELF magnetic field on spontaneous and amphetamine-induced locomotor and stereotypic activities in rats

The effects of chronic (7 days) exposure to an extremely low frequency magnetic field (ELF-MF, 50 Hz, 0.5 mT) on spontaneous and amphetamine-induced (1.5mg/kg, i.p.) locomotor and stereotypic activities in adult rats were examined by open field test for 2h on exposure days 1, 3, and 7. After 1 day of exposure to ELF-MF, the spontaneous locomotor activity was increased clearly at the first hour of observation and significantly at the second one as compared to the corresponding values in other series with ELF-MF and sham-exposed animals. After 7 days of exposure to ELF-MF, an amphetamine enhancing effect on the locomotor activity was significantly reduced at the second hour of observation as compared to that in 1-day- and sham-exposed rats treated with amphetamine. In contrast to the locomotor activity, the amphetamine-induced stereotypic behaviour in 7-day pre-exposed rats was significantly reduced at the first hour versus sham-exposed rats. While at the second hour of observation this effect was significant as compared to 1- and 3-day exposed animals (but not sham-exposed rats). Our results indicate that an extremely low frequency magnetic field is able to affect differently two types of behaviour, which are dependent on both the time course of exposure and the imbalance in the brain mediatory systems.     

地卓西平马来酸盐对雄性大鼠自发活动和前脉冲抑制及再认记忆的影响

目的 观察急性腹腔注射N-甲基-D-天冬氨酸(NMDA)受体拮抗剂地卓西平马来酸盐(MK-801)刘大鼠自发活动、感觉运动门控和物体再认记忆的影响,探讨MK-801模拟精神分裂症不同内表现型的适宜剂量.方法 成年雄性SD大鼠共104只,按照体质量采用分层随机化方法进行分组.(1)取SD大鼠48只,分为MK-801小剂量组、MK-801中剂量组、MK-801高剂量组和对照组,每组12只,观察不同剂量MK-801 (0.1、0.2、0.4 mg/kg)对大鼠自发活动的影响;(2)取SD大鼠32只,分为MK-801小剂量组、MK-801中剂量组、MK-801高剂量组和对照组,每组8只,观察不同剂量MK-801(0.1、0.2、0.4 mg/kg)对大鼠前脉冲抑制(PPI)的影响;(3)取SD大鼠24只,分为MK-801小剂量组和对照组,每组12只,观察小剂量MK-801 (0.1 mg/kg)对大鼠物体辨别测试的影响.结果 (1)中高剂量MK-801 (0.2,0.4 mg/kg)呈剂量依赖性诱导大鼠自发活动的增加以及PPI的损害(P＜0.05或P＜0.01),小剂量(0.1 mg/kg)组在自发活动和PPI上与对照组差异无统计学意义(P＞0.05).(2)小剂量MK-801组在物体辨别测试中对新物体的偏爱指数显著低于对照组[(57.79±10.66)％比(73.34±18.52)％,P＜0.05].结论 中高剂量MK-801可引起自发活动和感觉运动门控功能异常,而小剂量在排除运动系统异常的前提下可特异性地破坏大鼠的再认记忆,提示MK-801模拟精神分裂症的不同内表现型时应根据研究目的选择适宜剂量.     

Effects of novelty, pain and stress on hippocampal extracellular acetylcholine levels in male rats

In vivo microdialysis was used to assess the effects of Novelty, persistent pain (Formalin test) and stress (Restraint) on hippocampal acetylcholine (ACh) release. Experiments were carried out during the dark phase, i.e. during the active period of the animal, and consisted of four experimental phases: Baseline (30 min), Novelty (30 min), Formalin test (90 min) and Restraint (30 min); each animal was consecutively exposed to all phases. The extracellular levels of ACh in the dorsal hippocampus were estimated by measurement of its concentration in the perfusion fluid by high-performance liquid chromatography with electrochemical detection. The introduction to a new environment (Novelty) induced in all rats higher ACh levels than Baseline. Formalin treatment decreased ACh release only in animals considered ‘Inactive' during the Novelty phase while no modification in ACh release was observed in the ‘Active' ones. Restraint did not produce any modification of ACh release but increased Corticosterone plasma levels both in sham- and formalin-treated animals. Results indicate that Novelty, but not Formalin or Restraint, increases ACh release in the hippocampus and that the type of behavioral state displayed by the animal at the time of formalin injection determines the response of the septo-hippocampal cholinergic pathway.     

Non-linearity in combined effects of ELF magnetic field and amphetamine on motor activity in rats

The effects of short-term (15 min) pre-exposure of rats to extremely low-frequency magnetic field (ELF-MF, 50 Hz, 6 mT) on their motor (locomotor and stereotypic) activity induced by d-amphetamine sulphate (AMPH) at different doses (0.5, 1.5 and 4.5mg/kg, i.p.) were studied in the open field test. In saline-treated rats both parameters of motor activity were unaffected by ELF-MF irradiation. The rats pre-exposed to ELF-MF and injected with the lowest dose of AMPH showed the same locomotor activity as control animals, while their stereotypic behaviour was significantly elevated. ELF-MF in combination with AMPH at higher doses significantly enhanced motor activity when compared with values obtained in both control and combined experiments with the lowest dose of the drug. However, only combined locomotor effect at the middle dose of AMPH was significantly greater than those observed in corresponding experiments with AMPH alone. These results demonstrate that acute short-term exposure to ELF-MF is able to modify a motor activity in dependence on the extent of AMPH-induced neurotransmitter imbalance.     

Oxotremorine-induced modifications of the behavioral and neuroendocrine responses to formalin pain in male rats

In the present investigation, the antinociceptive effects of the muscarinic cholinergic agonist, oxotremorine, were evaluated in rats using the formalin test. In Expt. 1, two oxotremorine concentrations (0.1 and 0.2 mg/kg) and two administration times (15 and 1 min before formalin injection) were chosen. All spontaneous and formalin-evoked behavioral responses were considered. In Expt. 2, only the higher concentration of oxotremorine (0.2 mg/kg) was administered 15 or 1 min before the formalin test. The animals were killed 15, 30 or 60 min after formalin treatment. Blood was collected from the trunk to determine corticosterone plasma levels. Some brain areas (hypothalamus, septum and periaqueductal gray matter) were dissected for determination of the β-endorphin content. Oxotremorine induced a dose- and time-dependent reduction of all formalin-evoked responses: licking was decreased during both the first and second phases of the formalin test, flexing was decreased during the second phase by the higher concentration only and paw-jerk was decreased during the first phase by both concentrations. Rearing and line-crossing were significantly decreased by oxotremorine while exploratory activity was only partially reduced; self-grooming was increased. These effects on exploratory activity and self-grooming were abolished by formalin treatment. β-endorphin content in the septum was increased by oxotremorine administered 15 min, but not 1 min, before formalin-treatment. β-endorphin in the hypothalamus increased in all formalin-treated groups independently of oxotremorine administration. These results confirm, and extend to tonic pain, the analgesic effect exerted by oxotremorine on phasic responses. Because of the different effects on each formalin-induced response, they also indicate both spinal and supraspinal CNS sites of action.     

Improvements in motor behavioral tests during deep brain stimulation of the subthalamic nucleus in rats with different degrees of unilateral parkinsonism

Deep brain stimulation (DBS) improves motor performance in Parkinson's disease (PD) patients. To evaluate the effects of subthalamic nucleus (STN)-DBS on impaired motor behavior, we studied improvements in motor performance after delivery of unilateral stimulation to the STN in rats with mild and severe lesions of the nigrostriatal dopamine system caused by injecting 6-hydroxydopamine into the striatum. The rats were trained and performed motor behavioral tests including rotational behavior test, stepping test, and rotarod test before and after receiving DBS. We demonstrated that stimulation at a current strength of 200 microA, which stopped most of the D-amphetamine-induced rotational behaviors in these two groups, improved movement impairments in both the mild and severe groups and that the improvements in the mild group were significantly better than those in the severe group. More experimental and clinical studies are needed to evaluate the efficiency of STN-DBS for different stages of PD.     

Tumor angiogenesis and metastasis formation are associated with individual differences in behavior of inbred Lewis rats

There are large individual differences in cancer progression and it has been suggested that behavioral and psychological characteristics of cancer patients may contribute to the course of the disease. To get more insight in the contribution of behavioral characteristics to cancer progression, we investigated in rats, whether a stable behavioral trait characteristic is associated with NK cell activity, tumor angiogenesis, and tumor metastasis formation. Lewis rats were characterized based on locomotor activity in an open field. Rats in the upper and lower quartile were designated as high and low active rats. Low active animals had higher NK cell activity compared to their high active counterparts. In addition, we examined tumor angiogenesis by using a subcutaneous Matrigel implant containing MADB106 adenocarcinoma cells. Tumor Matrigel implants from low active animals contained significantly more hemoglobin compared to implants from high active animals, indicating a more pronounced angiogenic response in the low active animals. Finally, experimental lung metastasis formation was investigated by injecting MADB106 cells into the tail vein. Low active animals tended to develop more metastases. Moreover, low active animals developed significantly more tumors with a diameter larger than 2 mm, which is in line with higher angiogenic capacity. In conclusion, we demonstrated that individual differences in a stable behavioral trait are linked to individual differences in angiogenic capacity and tumor progression.     

Expression of endothelin-1 in the brain and lung of rats exposed to permanent hypobaric hypoxia

High-altitude hypoxia causes pulmonary hypertension in humans and animals. Endothelin-1 (ET-1) is a novel and long-lasting vasoconstrictor. However, no study has dealt with the effects of a hypobaric hypoxic environment (HHE) on ET-1 activity in the brain. We examined 134 male rats permanently exposed to the equivalent of 5500 m altitude for 1 to 8 weeks. In these HHE rats, the mean pulmonary arterial pressure was significantly raised. The level of ET-1 protein, measured by enzyme immunoassay, increased rapidly in the lungs on exposure to HHE, but decreased in the brain. The level of ET-1 mRNA, measured by semiquantitative RT-PCR, was raised at 1, 4, and 6 weeks' exposure in the lungs and at 4 or more weeks' exposure in 3 of 8 brain regions. By in situ hybridization and immunohistochemistry of brain sections, ET-1 mRNA and protein were detected in the endothelial cells, neurons, and astrocyte-like cells in control rats. In HHE rats, the immunoreactive intensity for ET-1 protein decreased rapidly with time in these cells within the brain, although a few weakly ET-1 protein-positive cells were detected until 8 weeks' exposure to HHE. Only a few weakly ET-1 mRNA-positive endothelial cells were detected in any HHE rats. Although the reactivity for ET-1 mRNA had decreased significantly in neurons and astrocyte-like cells at 1 and 2 weeks' exposure to HHE, it was again strong in both types of cells at 4 weeks' exposure to HHE. These results raise the possibility that during exposure to HHE, ET-1 production in the lung may play a role in the development of pulmonary hypertension, while a decrease in ET-1 production within the brain may help to protect neurons by preventing or limiting the constriction of cerebral microvessels during the hypoxia induced by HHE.     

4＇，5，7-三羟基异黄酮对蛛网膜下腔出血大鼠的神经保护和抗氧化作用研究

目的探讨4＇,5,7-三羟基异黄酮对蛛网膜下腔出血（SAH）后的神经保护作用。方法对大鼠单次枕大池注血模型分别以10mg／kg、50mg／kg浓度腹腔注射4＇,5,7-三羟基异黄酮,观察大鼠脑水肿、血脑屏障（BBB）的通透性、氧化应激和血红素氧合酶-1（HO-1）的变化情况。结果4＇,5,7-羟基异黄酮可以减轻SAH后脑水肿,降低BBB通透性、缓解氧化应激状态及减少HO-1的表达。结论4＇,5,7-三羟基异黄酮可能是通过提高内源性抗氧化酶的表达和抑制自由基的产生,从而在SAH中产生神经功能保护作用。     

A combined behavioral and morphological study on the effects of fetal asphyxia on the nigrostriatal dopaminergic system in adult rats

Fetal asphyxic insults in the brain are known to be associated with developmental neurological problems like neuromotor disorders. However, little is known about the long-term consequences of fetal asphyxia (FA). For that reason, the present study investigated the long-term effects of FA on motor behavior and dopaminergic circuitry. FA was induced at embryonic day 17 by 75-minute clamping of the uterine circulation. SHAM animals underwent the same procedure except for the clamping. This was followed by full-term vaginal delivery of animals in all groups (FA, SHAM and untreated controls). At 6 months, basal and amphetamine-induced locomotor activity was measured during open field testing. Brain sections were stained for tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP). TH-positive cells and GFAP-positive cells in substantia nigra pars compacta (SN_C) and striatum were counted using design-based stereology. Moreover, TH-immunoreactivity in the striatum was assessed by grey value measurements. Behavioral analysis demonstrated that SHAM and FA showed less basal and amphetamine-induced activity than controls. Histochemically, FA decreased the number of TH-positive neurons in the SN_C and lowered TH-positive in the striatum. Furthermore, more GFAP-positive cells were found in the SN_C and striatum in FA than in either control and SHAM groups. Additionally, FA animals showed ventriculomegaly associated with smaller white matter as well as grey matter volumes. The data show that FA was associated with deficits in both dopamine-related motor behavior and biochemistry. These alterations were associated with nigrostriatal astrogliosis. The present study demonstrates the sensitivity of the dopaminergic system towards FA.     

Role of lateral habenula in the regulation of exploratory behavior and its relationship to stress in rats

The lateral habenula is a major station conveying information between the limbic forebrain and midbrain. Bilateral lesions of the lateral habenula were found to increase exploratory behavior, including locomotor activity, rearing and hole-poke responses in rats. These effects were not due to an augmentation of general motor function, since the animal's performance on the Rota-rod treadmill was not significantly changed by the same manipulation. Lateral habenular lesion was also found to potentiate the effects of footshock stress on exploratory behavior in an open field. It is suggested that the lateral habenula probably plays an inhibitory role in the expression of certain emotion-related behaviors under normal and stressful situations.     

尼莫地平对新生大鼠缺氧缺血性脑损伤的防治作用

目的 :新生儿缺氧缺血性脑损伤 (hypoxic- ischemic brain damage,HIBD)严重危害新生儿的生命质量和健康 ,我们采用新生大鼠 IHBD模型 ,探讨尼莫地平对新生儿 HIBD的防治作用。材料和方法 :选用 7日龄 SD大鼠 32只 ,随机分为四组 :1伪手术组 ;2 IBD组 ;3HIBD+尼莫地平治疗 A组 ;4 HIBD+尼莫地平治疗 B组。除第一组外 ,其余各组均制成 HIBD模型 ,3、 4组用尼莫地平治疗 ,2 4小时后断头取脑组织 ,进行病理学检查 ,并测定脑组织中水分、钙、兴奋性氨基酸含量。结果 :1.2组与 1组相比 ,脑组织水分、钙、谷氨酸、天门冬氨酸含量均增高 (P<0 .0 1) ,神经细胞数明显减少 ,变性、坏死的细胞数明显增多 ;2 .3、 4组与 2组相比 ,病理学改变明显减轻。结论 :尼莫地平对新生大鼠 HIBD具有显著的防治作用 ,为新生儿 HIBD的防治提供了可靠的理论依据     

Cognitive impairment and increased brain neurosteroids in adult rats perinatally exposed to low millimolar blood alcohol concentrations

Epidemiological evidence suggests that adolescents and adults perinatally exposed to alcohol, even at low doses, show high prevalence of cognitive impairment and social behavior deficits, which may be in part related to alcohol-induced changes of the gamma-aminobutyric acid (GABA)ergic neurotransmission. The endogenous neurosteroid 3alpha-hydroxy,5alpha-pregnan-20-one (3alpha,5alpha-tetrahydroprogesterone/3alpha,5alpha-THP), a potent positive allosteric modulator of GABA(A) receptor function, is implicated in the physiological tuning of GABA-mediated fast inhibition and in various alcohol's actions in the brain. This study was undertaken to determine whether perinatal exposure to low millimolar blood alcohol concentrations alters cognitive skills (social discrimination and inhibitory avoidance tests), emotional reactivity (elevated plus maze test), and neurosteroid content in brain cortex and hippocampus of adult male offspring. Dams had access to a 3% alcohol solution or to an equicaloric sucrose solution from gestational day 15 to postnatal day 9. Eighty-day old alcohol-exposed male offspring exhibited impaired social recognition memory, but unchanged inhibitory avoidance performance and normal behavior on the elevated-plus maze. The concentrations of 3alpha,5alpha-THP and its precursor progesterone were more than doubled in brain cortex and hippocampus of alcohol-exposed rats, whereas in plasma only progesterone was increased. Thus, exposure to low millimolar blood alcohol concentrations has a long-lasting impact on the developing brain as it causes an impairment of social recognition as well as an increase of brain neurosteroid content in mature animals. The latter may be consequent to altered expression/activity of brain steroidogenic enzymes, as reflected by the enduring increase of the GABA(A) receptor-active neurosteroid 3alpha,5alpha-THP in brain cortex and hippocampus, but not in plasma. It is speculated that, by inducing a greater amplification of GABA(A) receptor function, the elevation of 3alpha,5alpha-THP brain content contributes to the cognitive impairment exhibited by adult alcohol-exposed offspring.     

Changes in EEG power spectra and behavioral states in rats exposed to the acetylcholinesterase inhibitor chlorpyrifos and muscarinic agonist oxotremorine

Organophosphates (OPs) inhibit acetylcholinesterase (AChE) activity causing cholinergic stimulation in the central nervous system (CNS). Cholinergic systems are crucial in electroencephalogram (EEG) generation and regulation of behavior; however, little is known about how OP exposure affects the EEG and behavioral states. We recorded EEG, core temperature and motor activity before and after exposure to the OP pesticide chlorpyrifos (CHP) in adult female rats implanted with telemetric transmitters. The recording and reference electrodes were placed in the occipital and frontal bones, respectively. The animals received CHP, 25 mg/kg, p.o., or oxotremorine (OX), 0.2 mg/kg, s.c. CHP led to a significant increase in delta (0.1-3.5 Hz), slow theta (4-6.5 Hz), gamma 2 (35.5-50 Hz), reduction in fast theta (7-8.5 Hz), alpha/sigma (9-14 Hz), beta 1 (14.5-24 Hz), beta 2 (24.5-30 Hz) and gamma 1 (30.5-35 Hz) powers, slowing of peak frequencies in 1-9 Hz range, hypothermia and decrease in motor activity. The drop in 7-14 Hz was associated with cholinergic suppression of sleep spindles. Changes in behavioral state were characterized by dramatic diminution of sleep postures and exploring activity and prolongation of quiet waking. There was recovery in all bands in spite of continued inhibition of AChE activity [44,45] in rats exposed to CHP. OX-induced EEG and behavioral alterations were similar to CHP except there was no increase in delta and the onset and recovery were more rapid. We did not find a correlation between the EEG and core temperature alterations. Overall, changes in EEG (except in delta band) and behavior following CHP were attributable to muscarinic stimulation. Cortical arousal together with increased quiet waking and decreased sleep after CHP occurred independently from inhibition of motor activity and lowering of core temperature.     

Spared place and object-place learning but limited spatial working memory capacity in rats with selective lesions of the dentate gyrus

We studied the cognitive performance of rats with colchicine-induced lesions of the hippocampal dentate gyrus (DG) on a range of spatial, non-spatial and mixed spatial/procedural tasks. Rats were assigned to three experimental groups receiving large colchicine lesions (7 microg per hippocampus), small colchicine lesions (1.75 microg per hippocampus) or sham lesions. Stereological estimates of cell density indicated that the colchicine treatments induced dose-dependent damage to the DG, while sparing in large part other hippocampal subfields. Remarkably, the behavioural results showed that the colchicine lesions did not affect the performance of rats in an object discrimination task, in an object-place associative task in which a familiar object was displaced from a given position nor in a spontaneous spatial discrimination task performed in the T-maze. However, rats in both lesion groups were severely impaired in a reinforced non-matching-to-position working memory task conducted in the T-maze. Importantly, performance in the working memory task correlated strongly with cell density in the DG but not with cell density in the CA1 and CA3 areas. Only rats with large-lesions showed a transient deficit in a reinforced rule-based conditional discrimination task. These data demonstrated that rats with selective lesions of the DG readily acquire and retain neural representations relative to objects and places but are specifically impaired in their ability to update rapidly and flexibly spatial information that is essential to guide goal-directed actions.     

Place learning and object recognition by rats subjected to transection of the fimbria-fornix and/or ablation of the prefrontal cortex

The acquisition of a water maze-based allocentric place learning task and an exploration based object recognition task were studied in four groups of rats: animals in which the fimbria-fornix had been transected, rats who had received bilateral ablations of the anteromedial prefrontal cortex, animals in which both of these structures had been lesioned, and a sham operated control group. None of the groups showed impairments of object recognition. Ablations of the prefrontal cortex caused a mild impairment in the acquisition of the place learning task. The two fimbria-fornix transected groups exhibited a severe impairment during the acquisition of this task. All groups reached criterion level task performance eventually. All groups were subjected to a number of behavioural and pharmacological challenges in order to elucidate the neural and cognitive mechanisms of this behavioural recovery. During a no-platform session both the fimbria-fornix transected group and the prefrontally ablated group demonstrated a normal preference for the former platform position. The combined lesion group, however, failed to show a similar preference for this position. The outcome of the pharmacological challenges demonstrated that while the task performance of all four groups relied equally on catecholaminergic mediation, only the task solution of the fimbria-fornix transected group was significantly impaired by disturbance of the catecholaminergic systems. The data indicated a high likelihood that prefrontal cortical mechanisms contribute to the recovery of allocentric place learning after fimbria-fornix transections.     

大鼠脑出血后行为学、组织学及脑水肿相关性研究

目的 探讨胶原酶诱导大鼠脑出血(ICH)后大鼠行为学的改变及其与脑水肿、组织学改变之间的关系.方法 纹状体区立体定向注射胶原酶建立大鼠纹状体ICH模型,动态观察大鼠ICH后28 d内的行为学、组织学及脑含水量改变.行为学评分采用前肢放置实验、Berderson评分法及角落转向实验,组织学观察采用HE染色,脑含水量测定采用干-湿重法.结果 (1)三种行为学试验结果均提示ICH后第2天大鼠出现严重的神经功能障碍,并在4周内神经功能逐渐恢复;(2)组织学观察显示ICH后存在组织损伤和修复过程;(3)脑含水量测定显示ICH后第2天脑水肿最为明显.在14 d内基本消退;(4)ICH后大鼠前肢放置实验评分和脑水肿之间存在负相关(20.774,P<0.05).结论 (1)大鼠ICH后神经功能存在损伤和修复过程;(2)大鼠ICH后神经功能改善仞期与脑水肿消退相关,而后期则可能与组织自身修复过程相关.