Behavioural therapy based on distraction alleviates impaired fear extinction in male serotonin transporter knockout rats

Background

The “biological susceptibility” model posits that some individuals, by genetic predisposition, are highly sensitive to environmental stimuli. Exposure to adverse stimuli leads to negative outcomes, and better outcomes follow favourable stimuli. Recent studies indicate that individuals carrying the low-activity (short; s) variant of the serotonin transporter (5-HTT)-linked polymorphic region (5-HTTLPR) show an enhanced vulnerability to posttraumatic stress disorder (PTSD). Simultaneously, they respond poorly to exposure therapy, the first-line treatment to enhance fear extinction in individuals with PTSD. Given that s-allele carriers also show improved adaptive responding when exposed to positive stimuli, we hypothesized that this trait could be used to offset impaired fear extinction.

Methods

We explored this hypothesis preclinically using wild-type and 5-HTT knockout (5-HTT^−/−) male rats (n = 36) that share behavioural similarities with 5-HTTLPR s-allele carriers. Subsequent to cued fear conditioning, animals were tested for short- (1 and 2 days postconditioning) and long-term (6 days postconditioning) fear extinction in the absence or presence of a secondary “distracting” stimulus predicting the delivery of sucrose pellets.

Results

Introducing a secondary stimulus predicting sucrose pellets that distracts attention away from the fear-predicting stimulus led to a long-lasting improvement of impaired fear extinction in 5-HTT^−/− male rats.

Limitations

The context-dependency of the efficacy of the “distraction therapy” was not tested. In addition, it remains to be clarified whether the positive valence of the distracting stimulus is critical for the distraction of attention or whether a neutral and/or novel stimulus can induce similar effects. Finally, although of lesser importance from a therapeutic perspective, underlying mechanisms remain to be elucidated.

Conclusion

These data indicate that positive environmental stimuli can be used to offset heightened responses to negative stimuli, particularly in individuals characterized by inherited 5-HTT downregulation and high sensitivity to environmental stimuli.     

Neonatal exposure to permethrin pesticide causes lifelong fear and spatial learning deficits and alters hippocampal morphology of synapses

Background

During the neurodevelopmental period, the brain is potentially more susceptible to environmental exposure to pollutants. The aim was to determine if neonatal exposure to permethrin (PERM) pesticide, at a low dosage that does not produce signs of obvious abnormalities, could represent a risk for the onset of diseases later in the life.

Methods

Neonatal rats (from postnatal day 6 to 21) were treated daily by gavage with a dose of PERM (34 mg/kg) close to the no-observed-adverse-effect level (NOAEL), and hippocampal morphology and function of synapses were investigated in adulthood. Fear conditioning, passive avoidance and Morris water maze tests were used to assess cognitive skills in rats, whereas electron microscopy analysis was used to investigate hippocampal morphological changes that occurred in adults.

Results

In both contextual and tone fear conditioning tests, PERM-treated rats showed a decreased freezing. In the passive avoidance test, the consolidation of the inhibitory avoidance was time-limited: the memory was not impaired for the first 24 h, whereas the information was not retained 72 h following training. The same trend was observed in the spatial reference memories acquired by Morris water maze. In PERM-treated rats, electron microscopy analysis revealed a decrease of synapses and surface densities in the stratum moleculare of CA1, in the inner molecular layer of the dentate gyrus and in the mossy fibers of the hippocampal areas together with a decrease of perforated synapses in the stratum moleculare of CA1 and in the inner molecular layer of the dentate gyrus.

Conclusions

Early-life permethrin exposure imparts long-lasting consequences on the hippocampus such as impairment of long-term memory storage and synaptic morphology.     

Propranolol’s effects on the consolidation and reconsolidation of long-term emotional memory in healthy participants: a meta-analysis

Background

Considering the pivotal role of negative emotional experiences in the development and persistence of mental disorders, interfering with the consolidation/reconsolidation of such experiences would open the door to a novel treatment approach in psychiatry. We conducted a meta-analysis on the experimental evidence regarding the capacity of the β-blocker propranolol to block the consolidation/reconsolidation of emotional memories in healthy adults.

Methods

Selected studies consisted of randomized, double-blind experiments assessing long-term memory for emotional material in healthy adults and involved at least 1 propranolol and 1 placebo condition. We searched PsycInfo, PubMed, Web of Science, Cochrane Central, PILOTS, Google Scholar and clinicaltrials.org for eligible studies from the period 1995–2012. Ten consolidation (n = 259) and 8 reconsolidation (n = 308) experiments met the inclusion criteria. We calculated effect sizes (Hedges g) using a random effects model.

Results

Compared with placebo, propranolol given before memory consolidation reduced subsequent recall for negatively valenced stories, pictures and word lists (Hedges g = 0.44, 95% confidence interval [CI] 0.14–0.74). Propranolol before reconsolidation also reduced subsequent recall for negatively valenced emotional words and the expression of cue-elicited fear responses (Hedges g = 0.56, 95% CI 0.13–1.00).

Limitations

Limitations include the moderate number of studies examining the influence of propranolol on emotional memory consolidation and reconsolidation in healthy adults and the fact that most samples consisted entirely of young adults, which may limit the ecological validity of results.

Conclusion

Propranolol shows promise in reducing subsequent memory for new or recalled emotional material in healthy adults. However, future studies will need to investigate whether more powerful idiosyncratic emotional memories can also be weakened and whether this weakening can bring about long-lasting symptomatic relief in clinical populations, such as patients with posttraumatic stress or other event-related disorders.     

利用条件恐惧应激的动物模型理解焦虑或害怕的神经生物学机制以及药物治疗的作用(英文)

The mechanisms underlying the etiology and pathophysiology of anxiety disorders - the most prevalent class of mental disorders - remain unclear.Over the last 30 years investigators have used the animal model of conditioned fear stress(CFS) to investigate the brain structures and neurotransmitter systems involved in aversive emotional learning and memory.Recent studies have focused on the neuronal circuitry and cellular mechanisms of fearful emotional experiences.This review describes the CFS paradigm,discusses the neural circuit and neurotransmission underlying CFS,and explains the mechanism of action of pharmacological treatments of CFS.The focus of the review is on the molecular mechanisms of fear extinction,a phenomenon directly implicated in the clinical treatment of anxiety.Based on our assessment of previous work we will conclude by considering potential molecular targets for treating symptoms of anxiety and fear.     

Inhibition of fear is differentially associated with cycling estrogen levels in women

Background

Although the prevalence of posttraumatic stress disorder (PTSD) is twice as high in women as it is in men, the role of estrogen in the risk for PTSD is not well understood. Deficits in fear inhibition and impaired safety signal learning may be biomarkers for PTSD. We examined menstrual cycle phase and serum estradiol levels in naturally cycling women while they were undergoing a novel conditioned inhibition procedure that measured their ability to discriminate between cues representing danger versus safety and to inhibit fear in the presence of safety cues.

Methods

Sample 1 included healthy participants in whom we compared inhibition of fear-potentiated startle during the follicular (lower estrogen) and luteal (higher estrogen) phases of the menstrual cycle. We used the same paradigm in a traumatized clinical population (sample 2) in whom we compared low versus high estradiol levels.

Results

In both samples, we found that lower estrogen in cycling women was associated with impaired fear inhibition.

Limitations

In the clinical sample, the low estradiol group was on average older than the high estradiol group owing to the random recruitment approach; we did not exclude participants based on hormonal status or menopause.

Conclusion

Our results suggest that the lower estrogen state during normal menstrual cycling may contribute to risk for anxiety disorders through dysregulated fear responses.     

Neuron-specific Sumo1–3 knockdown in mice impairs episodic and fear memories

Background

Growing evidence suggests that small ubiquitin-like modifier (SUMO) conjugation plays a key role in brain plasticity by modulating activity-dependent synaptic transmission. However, these observations are based largely on cell culture experiments. We hypothesized that episodic and fear memories would be affected by silencing SUMO1–3 expression.

Methods

To investigate the role of SUMO conjugation in neuronal functioning in vivo, we generated a novel Sumo transgenic mouse model in which a Thy1 promoter drives expression of 3 distinct microRNAs to silence Sumo1–3 expression, specifically in neurons. Wild-type and Sumo1–3 knockdown mice were subjected to a battery of behavioural tests to elucidate whether Sumoylation is involved in episodic and emotional memory.

Results

Expression of Sumo1–3 microRNAs and the corresponding silencing of Sumo expression were particularly pronounced in hippocampal, amygdala and layer V cerebral cortex neurons. The Sumo knockdown mice displayed anxiety-like responses and were impaired in episodic memory processes, contextual and cued fear conditioning and fear-potentiated startle.

Limitations

Since expression of Sumo1–3 was silenced in this mouse model, we need to verify in future studies which of the SUMO paralogues play the pivotal role in episodic and emotional memory.

Conclusion

Our results indicate that a functional SUMO conjugation pathway is essential for emotionality and cognition. This novel Sumo knockdown mouse model and the technology used in generating this mutant may help to reveal novel mechanisms that underlie a variety of neuropsychiatric conditions associated with anxiety and impairment of episodic and emotional memory.     

Posterior Cervical Fixation with a Nitinol Shape Memory Loop for Primary Surgical Stabilization of Atlantoaxial Instability: A Preliminary Report

Objective

To evaluate a new posterior atlantoaxial fixation technique using a nitinol shape memory loop as a simple method that avoids the risk of vertebral artery or nerve injury.

Methods

We retrospectively evaluated 14 patients with atlantoaxial instability who had undergone posterior C1-2 fusion using a nitinol shape memory loop. The success of fusion was determined clinically and radiologically. We reviewed patients'' neurologic outcomes, neck disability index (NDI), solid bone fusion on cervical spine films, changes in posterior atlantodental interval (PADI), and surgical complications.

Results

Solid bone fusion was documented radiologically in all cases, and PADI increased after surgery (p<0.05). All patients remained neurologically intact and showed improvement in NDI score (p<0.05). There were no surgical complications such as neural tissue or vertebral artery injury or instrument failure in the follow-up period.

Conclusion

Posterior C1-2 fixation with a nitinol shape memory loop is a simple, less technically demanding method compared to the conventional technique and may avoid the instrument-related complications of posterior C1-2 screw and rod fixation. We introduce this technique as one of the treatment options for atlantoaxial instability.     

Event-related potentials and changes of brain rhythm oscillations during working memory activation in patients with first-episode psychosis

Background

Earlier contributions have documented significant changes in sensory, attention-related endogenous event-related potential (ERP) components and θ band oscillatory responses during working memory activation in patients with schizophrenia. In patients with first-episode psychosis, such studies are still scarce and mostly focused on auditory sensory processing. The present study aimed to explore whether subtle deficits of cortical activation are present in these patients before the decline of working memory performance.

Methods

We assessed exogenous and endogenous ERPs and frontal θ event-related synchronization (ERS) in patients with first-episode psychosis and healthy controls who successfully performed an adapted 2-back working memory task, including 2 visual n-back working memory tasks as well as oddball detection and passive fixation tasks.

Results

We included 15 patients with first-episode psychosis and 18 controls in this study. Compared with controls, patients with first-episode psychosis displayed increased latencies of early visual ERPs and phasic θ ERS culmination peak in all conditions. However, they also showed a rapid recruitment of working memory–related neural generators, even in pure attention tasks, as indicated by the decreased N200 latency and increased amplitude of sustained θ ERS in detection compared with controls.

Limitations

Owing to the limited sample size, no distinction was made between patients with first-episode psychosis with positive and negative symptoms. Although we controlled for the global load of neuroleptics, medication effect cannot be totally ruled out.

Conclusion

The present findings support the concept of a blunted electroencephalographic response in patients with first-episode psychosis who recruit the maximum neural generators in simple attention conditions without being able to modulate their brain activation with increased complexity of working memory tasks.     

Have we met before? Neural correlates of emotional learning in women with social phobia

Background

Altered memory processes are thought to be a key mechanism in the etiology of anxiety disorders, but little is known about the neural correlates of fear learning and memory biases in patients with social phobia. The present study therefore examined whether patients with social phobia exhibit different patterns of neural activation when confronted with recently acquired emotional stimuli.

Methods

Patients with social phobia and a group of healthy controls learned to associate pseudonames with pictures of persons displaying either a fearful or a neutral expression. The next day, participants read the pseudonames in the magnetic resonance imaging scanner. Afterwards, 2 memory tests were carried out.

Results

We enrolled 21 patients and 21 controls in our study. There were no group differences for learning performance, and results of the memory tests were mixed. On a neural level, patients showed weaker amygdala activation than controls for the contrast of names previously associated with fearful versus neutral faces. Social phobia severity was negatively related to amygdala activation. Moreover, a detailed psychophysiological interaction analysis revealed an inverse correlation between disorder severity and frontolimbic connectivity for the emotional > neutral pseudonames contrast.

Limitations

Our sample included only women.

Conclusion

Our results support the theory of a disturbed corticolimbic interplay, even for recently learned emotional stimuli. We discuss the findings with regard to the vigilance–avoidance theory and contrast them to results indicating an oversensitive limbic system in patients with social phobia.     

Posterior Cervical Fixation with Nitinol Shape Memory Loop in the Anterior-Posterior Combined Approach for the Patients with Three Column Injury of the Cervical Spine : Preliminary Report

Objective

The authors reviewed clinical and radiological outcomes in patients with three column injury of the cervical spine who had undergone posterior cervical fixation using Nitinol shape memory alloy loop in the anterior-posterior combined approach.

Materials

Nine patients were surgically treated with anterior cervical fusion using an iliac bone graft and dynamic plate-screw system, and the posterior cervical fixation using Nitinol shape memory loop (Davydov™) at the same time. A retrospective review was performed. Clinical outcomes were assessed using the Frankel grading method. We reviewed the radiological parameters such as bony fusion rate, height of iliac bone graft strut, graft subsidence, cervical lordotic angle, and instrument related complication.

Results

Single-level fusion was performed in five patients, and two-level fusion in four. Solid bone fusion was presented in all cases after surgery. The mean height of graft strut was significantly decreased from 20.46±9.97 mm at immediate postoperative state to 18.87±8.60 mm at the final follow-up period (p<0.05). The mean cervical lordotic angle decreased from 13.83±11.84° to 11.37±6.03° at the immediate postoperative state but then, increased to 24.39±9.83° at the final follow-up period (p<0.05). There were no instrument related complications.

Conclusion

We suggest that the posterior cervical fixation using Nitinol shape memory alloy loop may be a simple and useful method, and be one of treatment options in anterior-posterior combined approach for the patients with the three column injury of the cervical spine.     

Modification of MRI criteria for multiple sclerosis in patients with clinically isolated syndromes

Background

The McDonald criteria include MRI evidence for dissemination in space and dissemination in time for the diagnosis of multiple sclerosis in young adult patients who present with clinically isolated syndromes (CIS) typical of the disease. Although a major advance, the criteria have limited sensitivity for making an early diagnosis.

Objective

To compare the performance of McDonald criteria and modified McDonald criteria for dissemination in space and time for assessing the development of clinically definite multiple sclerosis.

Methods

McDonald criteria were modified using the combination of a less stringent definition for dissemination in space and allowing a new T2 lesion per se after three months as evidence for dissemination in time. Modified and McDonald criteria were applied in 90 CIS patients at baseline and at three month follow up scans.

Results

Both criteria were highly specific (>90%) but the modified criteria were more sensitive (77% v 46%) and more accurate (86% v 73%).

Conclusions

These modified criteria should be evaluated in other CIS cohorts.     

The Changes in Range of Motion after a Lumbar Spinal Arthroplasty with Charité? in the Human Cadaveric Spine under Physiologic Compressive Follower Preload : A Comparative Study between Load Control Protocol and Hybrid Protocol

Objective

To compare two testing protocols for evaluating range of motion (ROM) changes in the preloaded cadaveric spines implanted with a mobile core type Charité™ lumbar artificial disc.

Methods

Using five human cadaveric lumbosacral spines (L2-S2), baseline ROMs were measured with a bending moment of 8 Nm for all motion modes (flexion/extension, lateral bending, and axial rotation) in intact spine. The ROM was tracked using a video-based motion-capturing system. After the Charité™ disc was implanted at the L4-L5 level, the measurement was repeated using two different methods : 1) loading up to 8 Nm with the compressive follower preload as in testing the intact spine (Load control protocol), 2) loading in displacement control until the total ROM of L2-S2 matches that when the intact spine was loaded under load control (Hybrid protocol). The comparison between the data of each protocol was performed.

Results

The ROMs of the L4-L5 arthroplasty level were increased in all test modalities (p < 0.05 in bending and rotation) under both load and hybrid protocols. At the adjacent segments, the ROMs were increased in all modes except flexion under load control protocol. Under hybrid protocol, the adjacent segments demonstrated decreased ROMs in all modalities except extension at the inferior segment. Statistical significance between load and hybrid protocols was observed during bending and rotation at the operative and adjacent levels (p < 0.05).

Conclusion

In hybrid protocol, the Charité™ disc provided a relatively better restoration of ROM, than in the load control protocol, reproducing clinical observations in terms of motion following surgery.     

Medial Temporal Atrophy and Memory Dysfunction in Poststroke Cognitive Impairment-No Dementia

Background and Purpose

It was recently reported that the prevalence of poststroke memory dysfunction might be higher than previously thought. Stroke may exist concomitantly with underlying Alzheimer''s disease (AD), and so we determined whether post-stroke memory dysfunction indicates manifestation of underlying subclinical AD.

Methods

Of 1201 patients in a prospective cognitive assessment database, we enrolled subjects with poststroke amnestic vascular cognitive impairment-no dementia (aVCIND; n=48), poststroke nonamnestic vascular cognitive impairment-no dementia (naVCIND; n=50), and nonstroke amnestic mild cognitive impairment (aMCI; n=65). All subjects had cognitive deficits, but did not meet the criteria for dementia. A standardized neuropsychological test battery and magnetic resonance imaging were performed at least 90 days after the index stroke (mean, 473 days). Visual assessment of medial temporal atrophy (MTA) was used as a measure of underlying AD pathology.

Results

The MTA score was significantly lower in the naVCIND group (0.64±0.85, mean±SD) than in the aVCIND (1.10±1.08) and aMCI (1.45±1.13; p<0.01) groups. Multivariable ordinal logistic regression analysis revealed that compared with naVCIND, aVCIND [odds ratio (OR)=2.69; 95% confidence interval (CI)=1.21-5.99] and aMCI (OR=5.20; 95% CI=2.41-11.23) were significantly associated with increasing severity of MTA.

Conclusions

Our findings show that compared with poststroke naVCIND, the odds of having more-severe MTA were increased for poststroke aVCIND and nonstroke aMCI.     

Serine Racemase and D-serine in the Amygdala Are Dynamically Involved in Fear Learning

Background

The amygdala is a central component of the neural circuitry that underlies fear learning. N-methyl-D-aspartate receptor–dependent plasticity in the amygdala is required for pavlovian fear conditioning and extinction. N-methyl-D-aspartate receptor activation requires the binding of a coagonist, D-serine, which is synthesized from L-serine by the neuronal enzyme serine racemase (SR). However, little is known about SR and D-serine function in the amygdala.

Schizandrin prevents dexamethasone-induced cognitive deficits

Objective To model glucocorticoid-induced cognitive impairment and evaluate the neuroprotection by schi-zandrin (Sch) against dexamethasone (Dex)-induced neurotoxicity in vivo and in vitro. Methods Cerebral cortical cells from neonatal Sprague-Dawley rats (within 24 hours after birth) were cultured for 9 days, and then treated with Dex (10 -4 , 10 -5 , 10 -6 or 10 -7 mol/L) for 24 h or pretreated with 10 -4 mol/L Dex for 24 h followed by 10, 20, 40, or 80 μmol/L Schfor 48 h. Cell viability was assessed using the MTT assay. Immunofluorescence and real-time PCR for MAP2 were performed to confirm the effects of Dex on neurite outgrowth. In vivo, kunming mice were randomly divided into six groups: control [(intragastric (i.g.) vehicle for 42 days]; Dex group I (5 mg/kg·d -1 Dex i.g. treatment for 28 days followed by i.g. vehicle for 14 days); Dex group II (Dex i.g. for 42 days); Dex + Sch (Dex i.g. for 28 days followed by 5, 15, or 45 mg/kg·d -1 Sch i.g. for 14 days). Learning and memory were assessed by Morris water maze test. Histological examination was used to assess pathology and apoptosis in neurons. Results Compared to the Dex groups, Sch increased cell viability in a dose-dependent manner, improved performance in the Morris water maze and ameliorated the morphological changes. Conclusion Sch has neuroprotective effects against insults induced by glucocorticoid.     

Aggressive Glucose Control for Acute Ischemic Stroke Patients by Insulin Infusion

Background and Purpose

Hyperglycemia after acute ischemic stroke (AIS) is associated with poor outcomes. However, there is no consensus as to the optimal method for glycemic control. We designed an insulin infusion protocol for aggressive glucose control and investigated its efficacy and safety.

Methods

We applied our protocol to patients within 48 hours after AIS or transient ischemic attack (TIA) with an initial capillary glucose level of between 100 and 399 mg/dL (5.6-22.2 mmol/L). An insulin solution comprising 40 or 50 U of human regular insulin in 500 mL of 5% dextrose was administered for 24 hours. Capillary glucose was measured every 2 hours and the infusion rate was adjusted according to a nomogram with a target range of 80-129 mg/dL (4.4-7.2 mmol/L). Changes in glucose and overall glucose levels during insulin infusion were analyzed according to the presence of diabetes or admission hyperglycemia (admission glucose >139 mg/dL or 7.7 mmol/L) by the generalized estimating equation method.

Results

The study cohort comprised 115 consecutive patients. Glucose was significantly lowered from 160±57 mg/dL (8.9±3.2 mmol/L) at admission to 93±28 mg/dL (5.2±1.6 mmol/L) during insulin infusion (p<0.05). Laboratory hypoglycemia (capillary glucose <80 mg/dL or 4.4 mmol/L) occurred in 91 (71%) patients, 11 (10%) of whom had symptomatic hypoglycemia. Although glucose levels were significantly lowered and maintained within the target range in all patients, overall glucose levels were significantly higher in patients with diabetes or hyperglycemia (p<0.05).

Conclusions

Our insulin-infusion protocol was effective in glycemic control for patients with AIS or TIA. Further modification is needed to improve the efficacy and safety of this procedure, and tailored intervention should be considered according to glycemic status.     

D-半乳糖和铝联合应用诱导大脑产生阿尔茨海默病样损伤(英文)

目的 D-半乳糖能制作亚急性衰老模型,铝具有神经毒性,但两者联合应用的作用未见报道。本研究旨在探讨D-半乳糖和铝联合应用对动物学习记忆、脑内生化和病理的影响,以及与单独应用D-半乳糖或铝所制作的动物模型相比较。方法昆明小鼠单独皮下注射D-半乳糖、单独灌胃铝以及既注射D-半乳糖又灌胃铝,制作动物模型,共给药8周或10周,10周后再停用药物6周。在第8、10、16周末,采用Morris水迷宫检测小鼠学习记忆能力,生化学方法检测脑内乙酰胆碱能系统,免疫组化法检测老年斑和神经原纤维缠结的形成。结果联合应用D-半乳糖和铝后,小鼠表现出明显的学习和记忆力障碍,并且其脑内乙酰胆碱水平降低,乙酰胆碱转移酶和胆碱脂酶活性下降,出现老年斑样和神经原纤维缠结样病理改变。停止给药后,其行为学、生化和病理改变至少能维持6周以上。结论小鼠中D-半乳糖和铝联合应用是一个有效的非转基因阿尔茨海默病(Alzheimer’sdisease,AD)模型,可用于AD病理研究和相关治疗药物的评价。     

Latent deleterious effects of binge drinking over a short period of time revealed only by electrophysiological measures

Background

Episodic excessive alcohol consumption (i.e., binge drinking) is now considered to be a major public health problem, but whereas short-and long-term harmful consequences of this behaviour are clearly established at medical, social and cognitive levels, the cerebral correlates of these impairments are still unknown. Our study explores the midterm cerebral effects of binge-drinking behaviours among young adults.

Methods

We selected 2 groups of first-year university students with no history of drinking habits, paired for psychological and behavioural measures on the basis of their expected alcohol consumption during the forthcoming academic year. The binge drinker group expected to have high personal alcohol consumption, whereas the control group expected low consumption. We used a test–retest paradigm within a 9-month period (session 1 in September 2005, session 2 in May 2006). At each testing session, we recorded auditory event-related potentials while the participants performed an emotional valence judgment task.

Results

There were no differences between the groups in behavioural or electrophysiological measures at baseline. After 9 months, the binge drinkers had significantly delayed latencies for all event-related potential components (P1, N2, P3b) of emotional auditory processing compared with the control group (p < 0.006), with no behavioural differences.

Limitations

As the present study explored the electrophysiological correlates of binge drinking with an emotional task only, the results will have to be extended to other cognitive processes using various experimental tasks.

Conclusion

We report the first direct evidence that short-term binge drinking can produce marked cerebral dysfunction undetectable by behavioural measures alone. The observed latency abnormalities, similar to those observed in long-term alcoholism, constitute an electrophysiological marker of slowed cerebral activity associated with binge drinking.     

Cognitive Dysfunction in 16 Patients with Carotid Stenosis: Detailed Neuropsychological Findings

Background

Impairment of cognitive function is often present in patients with carotid artery stenosis but the details of this dysfunction have rarely been reported. Our purpose was to elucidate the cognitive dysfunction in patients with unilateral severe carotid stenosis using comprehensive neuropsychological testing, and also to identify the specific underlying clinical and radiological factors.

Methods

We analyzed the results of neuropsychological testing, the clinical history, and MR findings in 16 consecutive patients with angiographically proven severe (70-99%) stenosis of the extra cranial internal carotid artery (ICA). Cognitive functions were examined using the Seoul Neuropsychological Screening Battery and the Neglect Battery. We excluded patients with cortical infarction and those with contra lateral ICA occlusion or severe stenosis.

Results

Our comprehensive neuropsychological testing revealed obvious cognitive deficits in all patients with unilateral severe ICA stenosis, the most common being frontal executive impairment. The mean cognitive score on the memory test was also significantly lower in patients with symptomatic ICA stenosis than in asymptomatic patients (29.33±10.98, mean±SD, p < 0.05). The total score on the global cognitive test was significantly lower in patients with an ischemic lesion on MRI than in no lesion patients (113.23±34.78, p < 0.05). The presence of symptoms related to the ICA stenosis was related to cognitive dysfunction even when there were no ischemic lesions on MRI. SPECT revealed ipsilateral cortical hypoperfusion in 9 of 12 patients (75%).

Conclusions

Cognitive deficits are common in patients with unilateral severe ICA stenosis. Our findings suggest that an additional mechanism beyond the structural lesion such as chronic hypoperfusion may affect cognitive function in patients with high-grade ICA stenosis.     

The neuroprotective effect of treatment of valproic Acid in acute spinal cord injury

Objective

Valproic acid (VPA), as known as histone deacetylase inhibitor, has neuroprotective effects. This study investigated the histological changes and functional recovery from spinal cord injury (SCI) associated with VPA treatment in a rat model.

Methods

Locomotor function was assessed according to the Basso-Beattie-Bresnahan scale for 2 weeks in rats after receiving twice daily intraperitoneal injections of 200 mg/kg VPA or the equivalent volume of normal saline for 7 days following SCI. The injured spinal cord was then examined histologically, including quantification of cavitation.

Results

Basso-Beattie-Bresnahan scale scores in rats receiving VPA were significantly higher than in the saline group (p<0.05). The cavity volume in the VPA group was significantly reduced compared with the control (saline-injected) group (p<0.05). The level of histone acetylation recovered in the VPA group, while it was significantly decreased in the control rats (p<0.05). The macrophage level was significantly decreased in the VPA group (p<0.05).

Conclusion

VPA influences the restoration of hyperacetylation and reduction of the inflammatory reaction resulting from SCI, and is effective for histology and motor function recovery.