Locomotor behavior following kindling in three different brain sites

Spontaneous and drug-induced interictal and post-ictal locomotor behavior of rats was investigated following electrical ‘kindling’ of different limbic structures at 3 brain sites which differ in the relative amount of innervation from dopamine cells of the ventral tegmentum: nucleus accumbens (N. Acc.), amygdala (AMYG), and dorsal hippocampus (DHPC). Kindling produced decreases in spontaneous post-ictal locomotion that did not appear to depend on the site of stimulation, but produced region specific attenuations in spontaneous interictal behavior as well as amphetamine-induced interictal and post-ictal responses. The most dramatic decreases were seen in N.Acc. kindled animals and the least dramatic were seen in rats kindled via DHPC. These data suggest that the mesolimbic dopamine system may participate in the changes in locomotion seen following kindled seizures, and may also provide a model for the study of human post-ictal and interictal behavior.     

Propranolol for the control of belligerent behavior following acute brain damage

The belligerence of 7 patients who had suffered an acute brain insult was effectively controlled by propranolol in doses of 60 to 320 mg per day. Of the 7 patients, 3 were treated in the acute stage after a stroke, a severe closed head injury, and a gunshot wound of the brain, respectively. A chronic postconcussion syndrome associated with chronic irritability was present in 2, and 2 were not chronically irritable but suffered from intermittent attacks of explosive rage in response to minor irritations. In all instances the belligerent behavior was controlled without inducing general sedation.     

The effect of acetylcholine depletion on behavior following traumatic brain injury

Rats were injected with either saline; A-4 (40 mg/kg, i.p.), a bis tertiary amine derivative of hemicholinium-3; or A-5 (50 micrograms/kg, i.p.), a bis quaternary amine derivative of hemicholinium-3, 1 h prior to moderate fluid percussion brain injury. A variety of reflexes and responses were measured up to 60 min following injury, and body weight and several neurological measures were taken daily up to 10 days following injury. Pretreatment with either A-4 or A-5 significantly attenuated components of transient behavioral suppression, as well as more enduring deficits in body weight and beam walk and beam balance performance. A-4 administered prior to fluid percussion was found to reduce striatal, but not pontine, acetylcholine content. A-5 did not significantly reduce acetylcholine content in either area. Both A-4 and A-5 pretreatment prevented a significant increase in acetylcholine content in the cerebrospinal fluid following fluid percussion injury; however, only A-5 significantly reduced plasma acetylcholine content. These results confirm cholinergic involvement in the production of both transient and longer-lasting behavioral deficits following traumatic brain injury. Furthermore, traumatic brain injury may allow plasma constituents to gain access to the central nervous system.     

大鼠脑出血后神经行为学和脑组织病理学改变的特点

目的观察大鼠脑尾壳核出血后不同时间点神经行为学和脑组织病理学的特点,为利用该模型研究脑出血的治疗措施提供参考依据。方法将成年SD大鼠随机分为正常组、假手术组和脑出血组;脑出血组大鼠通过立体定向术向脑内注入自体动脉血制成脑尾壳核出血模型,并按不同的再喂养时间(1d、3d、7d、14d、30d)分为5个亚组。采用神经功能评分和HE染色分别观察脑出血大鼠神经行为学和脑组织形态学的改变。结果与正常组和假手术组相比,脑出血组大鼠的神经行为学评分上升(1d和3d时P<0.05,7d、14d和30d时P>0.05)。脑出血后1～3d在尾壳核区域可见椭圆形或不规则血肿;7d出血灶内部分血细胞被吸收,血肿周围脑组织有胶质细胞增生;14d时出血区形成一个椭圆形或不规则囊腔;30d时病灶区仅存少量血细胞,出血周边区见胶质细胞进一步增多。结论脑出血后神经行为学的改变、血细胞的吸收及囊腔的形成与出血时间有关,此结果为选择时间窗治疗脑出血疾病提供了参考资料。     

Protective effects of brain hypothermia on behavior and histopathology following global cerebral ischemia in rats

The present experiments were designed to assess whether brain hypothermia can reduce the behavioral and histopathological deficits associated with global forebrain ischemia. Animals were subjected to 12.5 min of four vessel occlusion (4VO) with moderate hypotension, and brain temperature maintained at either 37°C (4VO-37) or 30°C (4VO-30). Behavioral tests designed to assess forelimb reflexes and sensorimotor function were given on post-operative weeks 2 and 4. Beginning in week 5, the rats were trained on a variety of navigation problems in the Morris water maze. Histopathological examination of the tissue 2 months following reperfusion revealed that 4VO-30 animals sustained substantial cell death in hippocampal region CA1 and moderate damage to the dorsolateral neostriatum. 4VO-30 animals showed minimal cell death in CA1 and neostriatum. There were no group differences for any of the sensorimotor measures, or for acquisition performance on either the simple place task or visible platform version of the water maze. In contrast, during acquisition of the learning set performance of 4VO-37 animals was impaired relative to either of the other groups, whereas the performance of 4VO-30 animals was not significantly different from the sham controls. These data suggest that moderate intra-ischemic brain hypothermia provides long-lasting protection from behavioral deficits as well as neuronal injury following transient global ischemia.     

Differential reinforcement of other behavior (DRO) to reduce aggressive behavior following traumatic brain injury

Severe brain injury can result in significant neurobehavioral and social functioning impairment. In rehabilitation settings, behavioral problems of aggression and nonadherence to therapeutic activities can pose barriers to maximal recovery of function. Behavioral interventions seem to be effective in reducing problem behavior among individuals recovering from severe brain trauma, but well-controlled studies examining the efficacy of such interventions are sparse. This article presents a single-case, multiple-baseline study of a differential reinforcement of other behavior (DRO) procedure in a 28-year-old, brain-injured male with aggressive behavior problems. The procedure successfully reduced the frequency of problem behavior by up to 74%, maintained at 1-month follow-up. Implications of this intervention for individuals with brain injury are discussed, and testing of this procedure using a between-group design seems indicated.     

Changes in emotional empathy, affective responsivity, and behavior following severe traumatic brain injury

This study was designed to examine the relationship between deficits in empathy, emotional responsivity, and social behavior in adults with severe traumatic brain injury (TBI). A total of 21 patients with severe TBI and 25 control participants viewed six film clips containing pleasant, unpleasant, and neutral content whilst facial muscle responses, skin conductance, and valence and arousal ratings were measured. Emotional empathy (the Balanced Emotional Empathy Scale, BEES: self-report) and changes in drive and control in social situations (The Current Behaviour Scale, CBS: relative report) were also assessed. In comparison to control participants, those in the TBI group reported less ability to empathize emotionally and had reduced facial responding to both pleasant and unpleasant films. They also exhibited lowered autonomic arousal, as well as abnormal ratings of valence and arousal, particularly to unpleasant films. Relative reported loss of emotional control was significantly associated with heightened empathy, while there was a trend to suggest that impaired drive (or motivation) may be related to lower levels of emotional empathy. The results represent the first to suggest that level of emotional empathy post traumatic brain injury may be associated with behavioral manifestations of disorders of drive and control.     

Chronic paranoid psychosis and dementia following interferon-alpha treatment of hepatitis C: a case report

Low-dose interferon-alpha is a standard therapy for hepatitis C. Psychotic disorders have been described as a rare complication of such treatments that resolve with its termination. Here, we present a patient without significant risk factors for interferon-alpha-induced serious mental disorders who developed a psychotic disorder with a cognitive impairment achieving the level of dementia after seven months of interferon-alpha therapy. The disturbances have persisted for three years despite cessation of interferon and introduction of antipsychotic treatment. The possibility of severe neuropsychiatric adverse effects of interferon-alpha therapy in a susceptible individual may necessitate regular psychiatric consultations during the treatment.     

Protein kinase C activity and subcellular distribution in rat brain following repeated electroconvulsive seizures.

Protein kinase C (PKC) activity was measured in samples of neocortex, cerebellum, and hippocampus from adult rats receiving a series of 10 electroconvulsive seizures (ECS). Rats were sacrificed immediately and at various intervals from 15 min to 24 h after the last seizure. From 77 to 84% of total PKC activity was found in the cytosol versus the membrane fraction. PKC activity in cerebellum was significantly higher than in neocortex (15%, P less than 0.05). Repeated ECS treatment did not affect total PKC activity nor its distribution between membrane and cytosolic fractions when compared with sham ECS controls. This finding is in keeping with reports that adrenergic-stimulated phosphoinositol turnover is not altered 24 h following repeated ECS.     

Amantadine improves water maze performance without affecting motor behavior following traumatic brain injury in rats

Amantadine, a dopamine agonist, is reported to have beneficial effects on the neurobehavioral sequelae of clinical brain injury. However, there are currently no published laboratory reports on its use in the assessment of functional or histopathological outcome following experimental traumatic brain injury (TBI). To this end, we examined the effects of daily amantadine treatment on functional recovery (motor and Morris water maze performance) and hippocampal neuronal survival following controlled cortical impact (CCI) injury (4 meters/sec, 2.7 mm tissue deformation). Male Sprague-Dawley rats were pretrained on motor performance tasks (beam balance and beam walking) one day prior to injury and tested on post-operative days 1-5. Additionally, all subjects were trained on the Morris water maze on post-operative days 14-18. Beginning one day after CCI injury or sham surgery, animals were injected once daily for 18 days with either amantadine (10 mg/kg, i.p.) or saline. The amantadine treatment regimen was ineffective in promoting motor recovery and increasing survival of hippocampal neurons in both the CA1 and CA3 regions following TBI, but did show improved swim latencies during the five days of water maze testing (Day 14 vs. Day 18, p < 0.01) when compared to saline controls. Mean (+/- SE) swim latencies on Day 18 were 15.12 +/- 2.8, 13.25 +/- 4.18, 70.83 +/- 11.1, and 38.5 +/- 3.55 sec for the sham/saline, sham/amantadine, injured/saline, and injured/amantadine treatment groups, respectively. Thus, while the daily administration of amantadine exhibited a neutral effect on motor behavior, it produced a modest attenuation of water maze performance deficits. This latter finding is consistent with published clinical data suggesting a beneficial effect on functional outcome with amantadine therapy.     

Fos immunoreactivity in the rat brain following consummatory elements of sexual behavior: a sex comparison

In the present study a comparison was made between the distribution of Fos immunoreactivity in the brain of female and male rats following successive elements of sexual behavior. The distribution of Fos immunoreactivity following either mounting, eight intromissions or one or two ejaculations was compared with that in control animals. In both females and males, Fos immunoreactivity was induced in the medial preoptic nucleus, posteromedial part of the bed nucleus of the stria terminalis, posterodorsal part of the medial amygdala, and the parvicellular part of the subparafascicular thalamic nucleus. In addition, Fos immunoreactivity in females was induced in the ventrolateral part and the most caudoventral part of the ventromedial nucleus of the hypothalamus and in the premammillary nucleus. Differences between females and males were detected in the phases of sexual activity that resulted in Fos immunoreactivity in these brain areas, allowing more insight in the nature of the sensory and hormonal stimuli leading to the induction of Fos immunoreactivity. The posteromedial bed nucleus of the stria terminalis appears to be involved in chemosensory investigation, while specific distinct subregions are only activated following ejaculation. In addition, the parvicellular subparafascicular nucleus and the lateral part of the posterodorsal medial amygdala appear to be involved in the integration of viscero-sensory input. The neural circuitries underlying sexual behavior in males and females appear to be similar in terms of integration of sensory information. In males the medial preoptic nucleus may be regarded as the brain area where the integration of sensory and hormonal stimulation leads to the onset of male sexual behavior, while in females the ventrolateral part of the ventromedial hypothalamic nucleus appears to have this function. In addition, Fos immunoreactivity was distributed in distinct clusters in subregions within various brain areas in males and females. This was observed especially in the posteromedial bed nucleus of the stria terminalis and posterodorsal medial amygdala, but also in the parvicellular subparafascicular nucleus, ventromedial hypothalamic nucleus and ventral premammillary nucleus. It appears that relatively small subunits within these nuclei seem to be concerned with the integration of sensory and hormonal information and may play a critical role in sexual behavior.     

Improvements in body composition,anthropometric measurements and lipid profile following discontinuation of clozapine

Background: Metabolic syndrome (obesity, glucose intolerance, insulin resistance and dyslipidaemia) is a well-known adverse effect of most antipsychotics. It is particularly common in patients treated with olanzapine and clozapine. Currently, the mechanisms underlying its development are not completely understood. Case report: We present a case of improved body composition (reduced amount of total body fat and visceral adipose tissue), anthropometric measurements (body weight, waist, abdominal and hip circumferences) and lipid profile in a 31-year-old man with schizophrenia following discontinuation of clozapine. During a combined treatment with clozapine, flupentixol and ziprasidone, a routine laboratory test revealed a severe dyslipidaemia (triglycerides > 1800 mg/dL; > 20.3 mmol/L), despite previous lipid-lowering therapy. This abnormality completely recovered after clozapine has been discontinued. Conclusions: Clozapine may cause severe, but reversible metabolic abnormalities, including obesity and hypertriglyceridaemia. Atypical antipsychotic-related lipid abnormalities may have a very rapid onset, occur in relatively young patients, with severe lipid derangements and have potential serious complications. This case confirms how important is to monitor metabolic parameters in patients taking antipsychotics. Discontinuation or switching to another antipsychotic medication may improve components of the metabolic syndrome.     

Taurine and vitamin C influence 8-nitroguanine brain expression following sub-chronic arsenic exposure in the mouse

BACKGROUND： Arsenic-induced overproduction of reactive nitrogen species results in damage to biomacromolecules in tissues. This is one of major mechanisms of toxic effects due to arsenic. It is assumed that taurine and vitamin C prevent overproduction of peroxynitrite （ONOO） and resist arseniasis by decreasing oxygen-free radical production. OBJECTIVE： To investigate the intervention effects of taurine and vitamin C on 8-nitroguanine （8-NO2-G） expression in the brain of mice exposed to arsenic. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Department of Occupational and Environmental Health, Dalian Medical University, China between March 2007 and July 2008. MATERIALS： As203, taurine, and vitamin C （Sigma, USA）, rabbit polyclonal anti-8-NO2-G antibody and goat anti-rabbit IgG （Dojindo, Japan） were used in this study. METHODS： A total of 40 healthy, Kunming mice were equally and randomly assigned to four groups Mice in the As203 group received drinking water containing 4 mg/L As2O3. Mice in the taurine and vitamin C groups received 150 mg/kg taurine and 45 mg/kg vitamin C, respectively, by gavage, twice per week, and simultaneously received As2O3. Mice in the control group were administered normal drinking water. MAIN OUTCOME MEASURES： Histopathological changes in brain tissues of mice were observed by hematoxylin-eosin staining. 8-NO2-G expression in brain tissues was determined by immunohistochemistry. RESULTS： Abnormal, histopathological changes were observed in brain tissue of mice from the As2O3 group, which included axonal loss, cell shrinkage, and karyolysis. The above-described changes were minimal in the taurine and vitamin C groups. 8-NO2-G expression was significantly greater in brain tissue from the As2O3 group compared with the control group （P 〈 0.05）, however, weak 8-NO2-G expression was observed in the taurine and vitamin C groups. CONCLUSION： Taurine or vitamin C protected against pathological changes and nucleic acid damage due to reactive nitrogen species in brain tissue of mice exposed to arsenic.     

Avoidance behavior and brain monoamines in fish

The crucian carp performs a typical avoidance behavior when exposed to olfactory cues from injured skin of conspecifics. They swim rapidly to the bottom and hide in available material. This work examines the effects of skin extract exposure and availability of hiding material on this behavior, and concomitant changes in brain monoaminergic activity in crucian carp. Individual fish were exposed to skin extract in aquaria with or without hiding material. Exposure to skin extract resulted in the expected avoidance behavior consisting of rapid movement towards the bottom of the aquarium. This lasted for 1-2 min. Activity then decreased below the level observed before exposure, suggesting a "freezing" type of avoidance behavior. This behavior was independent of availability of hiding material. Brain dopaminergic activity increased in telencephalon and decreased in the brain stem following skin extract exposure, again independent of availability of hiding material. However, fish kept in aquaria without hiding material showed an elevation of serotonergic activity in the brain stem and the optic tectum compared to fish with available hiding material. Absence of hiding material increased serotonergic activity also without exposure to skin extract. In aquaria with hiding material, the fish stirred up a cloud of fine sediments and showed a more pronounced decrease in locomotor activity in agreement with this being a more efficient freezing or immobile avoidance behavior. These results show that basic components of avoidance behavior and related brain changes are present in the fish brain, in accordance with the common phylogenetic roots of avoidance behavior in all vertebrates.