Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability

Ketamine exposure can lead to selective neuroapoptosis in the developing brain.p66ShcA,the cellular adapter protein expressed selectively in immature neurons,is a known pro-apoptotic molecule that triggers neuroapoptosis when activated.Sprague-Dawley rats at postnatal day 7 were subcutaneously injected in the neck with ketamine 20 mg/kg,six times at 2-hour intervals.At 0,1,3,and 6 hours after final injection,western blot assay was used to detect the expression of cleaved caspase-3,p66ShcA,and phosphorylated p66ShcA.We found that the expression of activated p66ShcA and caspase-3 increased after ketamine exposure and peaked at 3 hours.The same procedure was performed on a different group of rats.At the age of 4 weeks,spatial learning and memory abilities were tested with the Morris water maze.Latency to find the hidden platform for these rats was longer than it was for control rats,although the residence time in the target quadrant was similar.These findings indicate that ketamine exposure resulted in p66ShcA being activated in the course of an apoptotic cascade during the neonatal period.This may have contributed to the deficit in spatial learning and memory that persisted into adulthood.The experimental protocol was approved by the Institutional Animal Care and Use Committee at the University of Texas at Arlington,USA (approval No.A13.008) on January 22,2013.

Effect of Preemptive Ketamine Administration on Postoperative Visceral Pain after Gynecological Laparoscopic Surgery

The pain following gynecological laparoscopic surgery is less intense than that following open surgery; however, patients often experience visceral pain after the former surgery. The aim of this study was to determine the effects of preemptive ketamine on visceral pain in patients undergoing gynecological laparoscopic surgery. Ninety patients undergoing gynecological laparoscopic surgery were randomly assigned to one of three groups. Group 1 received placebo. Group 2 was intravenously injected with preincisional saline and local infiltration with 20 m L ropivacaine（4 mg/m L） at the end of surgery. Group 3 was intravenously injected with preincisional ketamine（0.3 mg/kg） and local infiltration with 20 m L ropivacaine（4 mg/m L） at the end of surgery. A standard anesthetic was used for all patients, and meperidine was used for postoperative analgesia. The visual analogue scale（VAS） scores for incisional and visceral pain at 2, 6, 12, and 24 h, cumulative analgesic consumption and time until first analgesic medication request, and adverse effects were recorded postoperatively. The VAS scores of visceral pain in group 3 were significantly lower than those in group 2 and group 1 at 2 h and 6 h postoperatively（P〈0.05 and P〈0.01, respectively）. At 2 h and 6 h, the VAS scores of incisional pain did not differ significantly between groups 2 and 3, but they were significantly lower than those in group 1（P〈0.01）. Groups 1 and 2 did not show any differences in visceral pain scores at 2 h and 6 h postoperatively. Moreover, the three groups showed no statistically significant differences in visceral and incisional pain scores at 12 h and 24 h postoperatively. The consumption of analgesics was significantly greater in group 1 than in groups 2 and 3, and the time to first request for analgesics was significantly longer in groups 2 and 3 than in group 1, with no statistically significant difference between groups 2 and 3. However, the three groups showed no significant difference in the incidence of shoulder pain or adverse effects. Preemptive ketamine may reduce visceral pain in patients undergoing gynecological laparoscopic surgery.

Effects of ketamine on mouse hippocampal inflammatory cytokines IL-6,IL-1β and TNF-α levels in acute and chronic administration models

OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile,ketamine has been showed to modulate the levels of inflammatory cytokines.Therefore,we sought to investigate whether the effects of ketamine on the central nervous system is associated with the inflammatory cytokines. METHODS We established acute(single or multiple intraperitoneal injection) and chronic(six months daily intraperitoneal injection) ketamine administration models in C57BL/6 mice,evaluated the spatial recognition memory and emotional response by applying the Y maze test and open field test. We analyzed the changes of inflammatory cytokines interleukin-6(IL-6),interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) levels in mouse hippocampus,employing Western blot,quantitative reverse transcriptase-polymerase chain reaction(qR T-PCR) and immunohistochemistry. RESULTS Ketamine induced spatial recognition memory deficit,reduced anxiety-like behaviors in mice after chronic administration,and it was dose-dependent. Moreover,we found that ketamine could increase the levels of mouse hippocampal inflammatory cytokines IL-6 and IL-1β after single,multiple and long-term administration in a dose-dependent manner. However,the level of TNF-α expressed differently in mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α,whereas multiple and long-term administration decreased it significantly. We considered that TNF-α might exist bi-directional regulatory pathway,which was associated with the dose and duration of ketamine administration. CONCLUSION Our results suggest that the alterations of inflammatory cytokines IL-6,IL-1β and TNF-α levels may be involved in the neurotoxicity of ketamine.

Efficacy of repeated intravenous esketamine in adolescents with anxious versus non-anxious depression

Background Patients with anxious major depressive disorder(MDD)are more likely to have poorer outcomes than those with non-anxious MDD.However,the effect of esketamine on adolescents with anxious versus non-anxious MDD has remained unknown.Aims We compared the efficacy of esketamine in adolescents with MDD and suicidal ideation,both anxious and non-anxious.Methods Fifty-four adolescents with anxious(n=33)and non-anxious(n=21)MDD received three infusions of esketamine 0.25mg/kg or active-placebo(midazolam 0.045 mg/kg)over 5 days,with routine inpatient care and treatment.Suicidal ideation and depressive symptoms were assessed using the Columbia Suicide Severity Rating Scale and the Montgomery-Asberg Depression Rating Scale.Multiple-sample proportional tests were used to compare the differences between groups on treatment outcomes 24 hours after the final infusion(day 6,primacy efficacy endpoint)and throughout the 4-week post-treatment(days 12,19 and 33).Results In subjects who received esketamine,a greater number of patients in the non-anxious group than the anxious group achieved antisuicidal remission on day 6(72.7%vs 18.8%,p=0.015)and day 12(90.9%vs 43.8%,p=0.013),and the non-anxious group had a higher antidepressant remission rate compared with the anxious group on day 33(72.7%vs 26.7%,p=0.045).No significant differences in treatment outcomes were observed between the anxious and non-anxious groups at other time points.Conclusions Three infusions of esketamine as an adjunct to routine inpatient care and treatment had a greater immediate post-treatment antisuicidal effect in adolescents with non-anxious MDD than in those with anxious MDD;however,this benefit was temporary and was not maintained over time.

Treatment Resistant Depression, Ketamine versus ECT

Recent studies have highlighted the increase in treatment resistant depression. Of particular concern is the rising trend of depression and suicide rates among Young Adults. Ketamine was approved for treatment resistant depression in 2019 by the US Food and Drug Administration. It received an additional indication for treatment of suicidality. While intranasal Ketamine is approved for depression, recent data about intravenous infusion of Ketamine in controlled inpatient settings has been promising. ECT has a long-standing trend for being used for resistant depression and recent comparison trials have revealed positive results when head-to-head comparisons are made with Ketamine. Future studies need to focus on patient selection and wherein treatment algorithm should Ketamine be selected as treatment modality.

Early and Late Postoperative Pain and Side Effects after Mastectomy: A Comparison of Ketamine and Thiamylal Administered for Anesthetic Induction

Objective: To compare acute and long-term postoperative pain and side effects in patients undergoing mastectomy for breast cancer under general anesthesia induced with ketamine or thiamylal. Methods: Twenty four ASA physical status I-III patients undergoing mastectomy were randomly assigned to one of two groups. Ketamine group received intravenous ketamine, 1 mg/kg, and thiamylal group received intravenous thiamylal, 4 mg/kg, at the induction of general anesthesia. Anesthesia was maintained with sevoflurane, N2O and fentanyl. The intensity of pain was assessed by using visual analog scale (VAS) 3 and 16 hr and 2, 3 and 4 weeks after surgery. Postoperative side effects, including nausea, vomiting and hallucination were also recorded. Results: At 16 hr after surgery, VAS in ketamine group was significantly lower than that in thiamylal group. However, there were no statistically significant differences between the two groups in the VAS at 3 hr and 2, 3 and 4 weeks after surgery. There were no differences in the incidence of side effects such as nausea, vomiting and hallucination between the two groups. Conclusion: Intravenous ketamine at the induction of anesthesia could reduce acute postoperative pain but not long-term pain after mastectomy.

Comparative efficacy of ketamine,lidocaine,acetaminophen,and dexmedetomidine combined with morphine patient-controlled analgesia in treating opium-addicted patients undergoing tibia fracture surgery:A randomized clinical trial

Objective:To compare the effect of ketamine,lidocaine,acetaminophen,and dexmedetomidine combined with morphine patient-controlled analgesia for opium addicts after tibial fracture surgery.Methods:This double-blind clinical trial included opium-addicted patients undergoing tibia fracture surgery.Patients were recruited and randomized to four different groups including the ketamine group,the lidocaine group,the acetaminophen group,and the dexmedetomidine group.The hemodynamic parameters such as heart rate(HR),mean arterial pressure,and arterial SaO2,alongside visual analog scale pain scores,sedation assessed by Ramsay score,nausea and vomiting,and opioid use were recorded and compared among the four groups.Results:This study included 140 patients,aged 37(32,41)years,with 92 males and 48 females,and each group had 35 patients.Dexmedetomidine-sedated subjects had the lowest blood pressure from 1 to 24 h after surgery,decreased HR at 12 and 24 h after surgery,and more satisfactory sedation(P<0.05).Notwithstanding no significant difference was noted in the pain scores,or nausea and vomiting among the groups(P>0.05).Conclusions:Dexmedetomidine has a better sedation effect compared to ketamine,lidocaine,and acetaminophen for pain control,but the final choice hinges on the patients’physical condition and the anesthesiologist's preference.Clinical registration:It is registered in Iranian Registry Clinical Trial by code IRCT20141209020258N146.

Absence of Ketamine Effects on Learning &Memory Following Exposure during Early Adolescence: A Preliminary Report

Traditionally, ketamine was considered useful as a dissociative anesthetic. More recently, ketamine has been examined for its effects as a fast-acting antidepressant, for treatment-resistant depression, and as a non-opiate treatment of chronic pain. Unfortunately, ketamine has enjoyed popularity as a recreational drug among both adolescents and young adults. While some research suggests the use of this drug during neurodevelopment is not without consequence, relatively little work has been conducted to examine the chronic effects of ketamine on the adolescent brain at different stages of neural development. Using a rodent model of development, we probed the effects of early adolescent exposure to ketamine. Between postnatal days 22 to 40, a period comprising early to mid-adolescence, rats were exposed to one of two doses of ketamine or saline. Beginning at 90 days of age and drug free for 50 days, a series of neuropsychological assessments were employed to examine general activity, spatial navigation, as well as nonspatial response learning. Contrary to prediction, except for differences in general activity levels, no spatial or nonspatial impairments were found among the drug- and saline-treated animals. The present results are considered in light of ketamine-associated effects found in a related study with older adolescent rats and the role of drug exposure during different points in adolescent brain development.

Intrathecal co-administration of ketamine and morphine preventing activation of astrocytes and decreasing releases of IL-1β and IL-6 from spinal cord in rats of morphine tolerance

Objective： To investigate the effects of intrathecal administration of ketamine, a non-competitive N-methy-D-aspartate receptor antagonist, combined with morphine on the activation of astrocytes and releases of IL-1β and IL-6 from spinal cord in the rats of morphine tolerance. Methods： Twenty-seven Sprague-Dawley male rats were randomly divided into sham-operated, morphine tolerance, and morphine plus ketamine group. The subarachnoid catheterication of all the rats was prepared by the method of Jianping Yang. Morphine 20μg in 10μl was adminstrated intrathecally to induce spinal morphine tolerance once daily for 5 consecutive days. Morphine and ketamine 250μg in 10μl total volume was given in morphine plus ketamine group. Three groups all received intrathecal morphine 5μg in 10μl for morphine challenge test at 24h after last administration of the morphine. After morphine challenge test, lumbar spinal tissues were taken for measurement of glial fibrillary acidic protein （GFAP） of astrocyte in lumbar spinal horn cord by immunohistochemistry and IL-1β and IL-6 of spinal cord by ELISA. Results： The decrease of %MPE induced by chronic intrathecal morphine was inhibibed by ketamine and hyperalgesia and allodynia induced by morphine-withdrawl were alleviated. The average areas, the average absorbency （A^-）, the integral absorbency （A） of GFAP immuno-reactive cells in the dorsal horn, and IL-1β and IL-6 of spinal cord were significantly larger in morphine tolerance group than in morphine plus ketamine group. Conclusion：Co-administration of ketamine and morphine enhance antinociceptive effect of morphine and prevent the development of morphine tolerance. Ketamine might attenuate the activation of astrocytes and inhibit the release of IL-1β and IL-6 from spinal cord in repeated intrathecal morphine rats.

Neuropsychological Assessment of Learning and Memory in Rats Following Ketamine Exposure during Late Adolescence

With the prevalent issue of drug abuse in society, research regarding the effects of ketamine, a drug frequently abused by youth in club settings, has increased. Despite its potential for misuse, ketamine has demonstrated potential as a fast-acting antidepressant and seems to work well for relieving treatment-resistant depression. However, previous research has shown ketamine use may cause impairments in frontal and medial temporal lobe functioning, leading to problems with memory. While under the influence of ketamine, individuals also display problems with spatial working memory when compared to individuals not dosed with ketamine. The majority of previous research has examined the short-term impact of ketamine use with studies on neurodevelopment largely confined to postnatal exposure. In the present study, the long-term effects on memory caused by repeated ketamine exposure during late adolescence were examined. Rats were used as nonhuman models in order to investigate the cognitive risks resulting from chronic use of ketamine. The results indicated that low-ketamine dosed rats demonstrated significantly better spatial memory recall compared to high-ketamine dosed rats. In addition, high-ketamine dosed rats appeared to struggle more with working memory than the rats in the low-ketamine and control groups. Similarly, both drug groups showed significantly more working memory and reference memory errors than the control group. This indicates that higher doses of ketamine during late adolescence may cause working and spatial memory impairments later in life.

Recent Advances in Ketamine Research: An Update

Ketamine is a sedative N-methyl-D-aspartate receptor antagonist, considered as a dissociative anesthetic medication. Ketamine inhibits the voltage-gated Na+ & K+ channels and serotonin and dopamine re-uptake and affects specific receptors, such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and aminobutyric acid A receptors. It is commonly administered by a parenteral route. On administration, ketamine has particular properties that are potentially involved during anesthetic induction including the enhancement of descending inhibition and anti-inflammatory effects. Recent literature reviews report that ketamine possesses various clinically beneficial properties. Sub-dissociative dose/Lower dose of ketamine (LDK) has potential as well as safe effects in clinical practice for the management of acute and chronic pain in postoperative room as well as Emergency Department (ED), along with cognitive function and depression in Psychiatric Department. Moreover, pharmacology of ketamine includes bronchodilators, neuro-protective actions, anti-shock, anti-suicide, and anti-tumor action immune system disorder. The purpose of this review is to illustrate recent advances in mechanism of action, mode of administration and indication of clinical uses of ketamine. In this article various new uses of ketamine have been shown, mainly related to its NMDAR antagonism and the clinical implementation and significance of low dose/sub dissociative dose of ketamine. In future, beyond being used as the adjuvant general anesthesia, it also can be used as a rapid acting antidepressant and anti-suicidal agent for mental disorders, and adjuvant analgesia to avoid potential risk and side effects of opioids in emergency department and in post-operative care.

Virtual Reality as an Adjunct to Ketamine Infusion Therapy Increases Patient Satisfaction in the Management of Chronic Pain and Depression: A Retrospective Pilot Study

The management of patients with concomitant chronic pain (CP) and Major Depressive Disorder (MDD) remains challenging for clinicians. Current chronic pharmacologic management is often unsuccessful, or has intolerable side effects to the patients. While not restricted to patients with chronic pain, these patients are often diagnosed with depression, presenting with symptoms such as poor mood, anhedonia, and altered cognitive processes. It is estimated that a substantial proportion of treated patients do not derive a substantive benefit from traditional pharmacological treatments for depression. The present study involved a retrospective review of cases, exploring the patient-reported satisfaction with and tolerability of a novel use of virtual reality (VR), coined KVR, as an adjunct to intravenous ketamine infusion therapies. Specifically, the ketamine-virtual reality protocol was employed as a potential adjunctive intervention for patients suffering from chronic pain and depression. Visual Analog Scores (VAS) associated with pain were significantly lower on the third than on the first assessment day. Montgomery-?sberg Depression Rating Scale (MADRS) scores improved following infusion and across days (i.e., sessions). Lastly, 2/3 of patients preferred the use of VR with their ketamine infusion. The results are considered in terms of implementing prospective studies to examine whether the combination therapies have a synergistic benefit and the nature and magnitude of clinically meaningful treatment effects, if any.

Sub-dissociative dose ketamine administration for managing pain in the emergency department

BACKGROUND： We describe our experience of utilizing sub-dissociative dose ketamine （SDK） in managing a variety of acute and chronic painful conditions in the emergency department （ED）. METHODS： A descriptive study was conducted in our ED over a period of seven years （2010-2016） by retrospectively reviewing charts of patients aged 18 and older presenting to the ED with painful complaints and receiving SDK analgesia. Primary data analyses included type of SDK administration （intravenous push [IVP], short-infusion [SI] or continuous infusion [CI]）, dosing, rates of analgesic utilization before and after SDK administration, and adverse effects. RESULTS： Three hundred sixty-two patients were enrolled in the study. Mean ketamine doses given by IVP, St and CI were 26.3 rag, 23.4 rag, and 11.3 rag. The mean duration of CI was 135.87 minutes. The percentage of patients not requiring post-SDK analgesia increased by 16%, 18%, and 37% in IVP, SI and CI groups. Adverse effects were recorded for 13% of patients. CONCLUSION： SDK administered by IVP, SI, and CI in the ED for a variety of painful conditions is a feasible analgesic modality in the ED that is associated with a decrease in overall requirements of post-ketamine analgesia and opioid sparing.

Administration of Nebulised Ketamine for Managing Pain in the Intensive Care Unit of Obstetrics and Gynaecology

Introduction: The use of inhaled ketamine to manage a variety of painful conditions has been endorsed by the American College of Emergency Physicians and the American Academy of Emergency Medicine. Nebulized analgesia has multiple benefits, including rapid, effective and titratable analgesic delivery. The aim of our study is to assess the efficacy and safety of intranasal analgesic-dose ketamine compared to multimodal analgesia in patients presenting with acute postoperative pain or headache after a spinal anaesthetic in the intensive care unit of obstetrics and gynaecology. Materials and Methods: This was a prospective descriptive study, with hospital Ethics Committee approval and written informed consent from study participants. We compared the effect of nebulized ketamine and multimodal analgesia postoperatively in 120 patients belonging to the physical status I - II of the American Society of Anesthesiologists, in the intensive care unit of obstetrics and gynaecology, at the Ibn Rochd University Hospital Center in Casablanca from June 2021 to June 2022. Results: We included 120 patients in our study divided into two groups of 60 patients: the average age was 35 years, with extremes ranging from 18 to 45 years, All patients were hospitalized for postoperative care: all women underwent locoregional anaesthesia with a standard dose according to the service protocol (10 mg of bupivacaine, 25γ of fentanyl, 100γ of morphine), where pain was the common denominator. Among these patients, 59 were admitted for management of postpartum haemorrhage, 43 for postoperative monitoring, 15 for post-spinal anaesthesia headache and 3 for pelviperitonitis. The results of the pain assessment 30 minutes after the ketamine nebulization were marked by a request for analgesia in 12 patients, which is 20% of group A, including 5 patients, whose visual analogue scale (VAS) on admission was between 5 and 7, and 7 patients whose VAS at admission was ≥8;all these patients received a second dose of ketamine by nebulization;the evaluation 30 min after the second dose was marked by a request for analgesia in 4 patients, which is 7% of Group A;in all these patients the VAS at admission was ≥8. Of the total number of patients of Group A, only 4 received morphine when they were requested for analgesia after the second dose of nebulized ketamine. Conclusion: The primary outcome of nebulized ketamine use is a significant reduction in VAS pain score. We believe that nebulized ketamine has a potential effect of reducing pain in the intensive care unit of obstetrics and gynaecology;this may be an additional analgesic modality for clinicians to provide rapid, effective and non-invasive pain relief.

Effect of Local Wound Infiltration with Ketamine versus Dexmedetomidine Added to Bupivacaine on Inflammatory Cytokines, a Randomized Clinical Trial

Background: Ketamine or dexmedetomidine as an adjuvant to bupivacaine in local wound infiltration attenuated postoperative stress response, especially with ketamine in patients undergoing total abdominal hysterectomy. Objectives: Compare effect of local wound infiltration with ketamine or dexmedetomidine added to bupivacaine to bupivacaine alone on inflammatory cytokine response after total abdominal hysterectomy. Methods: Sixty female patients with endometrial carcinoma underwent total abdominal hysterectomy and scheduled to receive local wound infiltration before wound closure either with one of three;40 ml of 0.25% bupivacaine alone (C Group) or with the addition of 2 mg/kg ketamine (K Group) or 2 μg/kg dexmedetomidine (D Group). After extubation, they were followed up for postoperative interleukin 6 (IL6), IL1β, IL10, and TNF-α levels were assessed at baseline, pre-infiltration, 6, and 24 h by blood samples obtained from each patient, hemodynamic variables, analgesic profile and side effects. Results: Inflammatory cytokines response was attenuated in K and D groups, evidenced by decreased mean pro-inflammatory cytokines IL6, TNF-α, and increased anti-inflammatory IL10 at 6 and 24 h postoperatively compared to pre-infiltration levels (p ≤ 0.01) with preservation of IL1β at its preoperative level (p > 0.05). Attenuation was more in K and D groups than in the C group and was highest in the K group with decreased 1st request, total morphine consumption without serious side effect. Conclusion: Local wound infiltration with ketamine or dexmedetomidine added to bupivacaine has a good postoperative analgesic profile and attenuated cytokines inflammatory response more than bupivacaine alone after total abdominal hysterectomy, with highest attenuation in ketamine group.

Evaluation of the Use of Ketamine for Acute Pain in the Emergency Department at a Tertiary Academic Medical Center

Introduction: At subdissociative doses of 0.1 - 0.5 mg/kg, ketamine provides effective analgesia when used alone or as an adjunct to opioid analgesics without causing cardiovascular or respiratory compromise. Ketamine is a beneficial analgesic agent in the emergency department (ED), particularly in patients with opioid-resistant pain or polytrauma patients who are hemodynamically unstable. Purpose: The purpose of this study was to evaluate current practice and describe clinical outcomes associated with the use of low-dose ketamine for acute pain in the ED. Methods: Adult patients receiving ketamine were retrospectively evaluated between March 1, 2012 and March 31, 2013. Patients were included if they were ordered for ketamine in the ED to treat acute pain. Outcomes included dose administered, cumulative doses, concurrent opioid administration, and any efficacy or adverse events documented after the administration of ketamine. Continuous variables are reported as mean (standard deviation [SD]) or median (interquartile range [IQR]). Results: A total of 46 patients were evaluated for inclusion. Of the 25 patients included, 38 doses of ketamine were documented. The mean age was 41 years old with 64% of the patients being female. The average initial ketamine dose was 0.12 ± 0.06 mg/kg and 8 (32%) patients received multiple doses of ketamine (1.5 ± 0.8 doses per patient). Ketamine was added to opioid therapy in 23 (92%) patients. Pain scores decreased post administration of ketamine from 10 (9 - 10) to 5 (4 - 7). Adequate pain relief was documented in 11 (44%) patients (felt comfortable going home);partial pain relief was noted in 5 (20%) patients;3 (12%) patients reported no pain relief;3 (12%) patients were able to have a procedure done, and efficacy was not documented in 3 (12%) patients. Anxiety and agitation were documented in 2 (8%) patients. No adverse outcomes were documented in 84% of patients. Conclusion: Administration of low-dose ketamine for acute pain in the ED demonstrated improvement in patients’ pain scores with minimal documented adverse outcomes.

Ketamine和Bicucullin对帕金森模型的影响

目的 为帕金森氏病的发病机理及兴奋性氨基酸受体拮抗剂对帕金森氏病的防治提供理论根据。方法 本实验采用MPTP腹腔注射建立C57BL小黑鼠帕金森氏病模型的过程中 ,同时用兴奋性氨基酸NMDA受体拮抗剂Ketamine和GABA受体拮抗剂Bicucullin ,观察其帕金森行为症状、病理变化及生化改变。结果 Ketamine加MPTP组和Bicucullin加MPTP组及MPTP组和生理盐水组比较 ,上述指标都有明显改变。结论 NMDA受体拮抗剂对小鼠帕金森氏病模型具有防治作用 ,GABA神经元的功能降低可加重帕金森氏病的症状。

Effect of propofol and ketamine anesthesia on cognitive function and immune function in young rats

Objective:To investigate the effects of propofol and ketamine on the cognitive function and immune function in young rats.Method:A total of 80 young rats were randomly divided into four groups:Control group,ketamine group(experimental group A),propofol group(experimental group B),ketamine and propofol group(experimental group Q.All rats had continuous injection for three times,serum IL-2,IL-4 and II.-10 and whole brain IL-I P level,hippocampal neuronal apoptosis level were measured.The cognitive ability in rats was tested by water maze.Results:Water maze test showed on the 1st d,the maze test latency of the control group,the experimental group B and the experimental group C water were decreased gradually;Compared with the control group after 3 days,the latency of the experimental group A,experimental group B and experimental group C were all decreased,the crossing circle times were also reduced.Hippocampal neuron apoptosis were(2.3±1.7)%,(14.7±6.9)%,(4.2±3.3)%,(10.2±4.8r%in control group,experimental group A,experimental group B and experimental group C,respectively.The neurons apoptosis of experimental group A was significantly increased.The serum IL-4 and 1L-10 of the experimental group A,experimental group B and experimental group C after anesthesia were significantly higher than the control group.The whole brain IL-1β of the experimental group A,experimental group B and experimental group C were significantly lower than the control group.Conclusions:Propofol can reduce anesthesia effect of ketamine on the cognitive function and immune function in the young rats.

基于ADE优化的IPMSM全速域无传感器控制

为了实现内置式永磁同步电机(IPMSM)全速域的无传感器控制和切换速域的平滑过渡,提出了一种基于自适应差分进化(ADE)算法优化的复合控制方法。分别在零低速域、中高速域采用旋转高频电压注入法和滑模观测器法来对电机转速和转子位置进行估算,并在切换速域采用基于ADE算法的权重系数优化法来实现上述两种控制方法的平滑切换,从而实现IPMSM全速域无传感器控制。仿真结果表明:提出的复合控制方法能够实现电机全速域的无感控制和切换速域的平滑过渡,且具有良好的稳定性。

Ketamine induces tau hyperphosphorylation at serine 404 in the hippocampus of neonatal rats

Male Wistar 7-day-old rats were injected with 40 mg/kg ketamine intraperitoneally, followed by three additional injections of 20 mg/kg ketamine each upon restoration of the righting reflex. Neonatal rats injected with equivalent volumes of saline served as controls. Hippocampal samples were collected at 1,7 or 14 days following administration. Electron microscopy showed that neuronal structure changed noticeably following ketamine treatment. Specifically, microtubular structure became irregular and disorganized. Quantitative real time-PCR revealed that phosphorylated tau mRNA was upregulated after ketamine. Western blot analysis demonstrated that phosphorylated tau levels at serine 396 initially decreased at 1 day after ketamine injection, and then gradually returned to control values. At 14 days after injection, levels of phosphorylated tau were higher in the ketamine group than in the control group. Tau protein phosphorylated at serine 404 significantly increased after ketamine injection and then gradually decreased with time. However, the levels of tau protein at serine 404 were significantly greater in the ketamine group than in the control group until 14 days. The present results indicate that ketamine induces an increase of phosphorylated tau mRNA and excessive phosphorylation of tau protein at serine 404, causing disruption of microtubules in the neonatal rat hippocampus and potentially resulting in damage to hippocampal neurons.