In order to characterize sleep and the cognitive patterns in patients with acute minor thalamic infarction （AMTI）, we enrolled 27 patients with AMTI and 12 mat- ched healthy individuals. Questionnaires about sleep a...In order to characterize sleep and the cognitive patterns in patients with acute minor thalamic infarction （AMTI）, we enrolled 27 patients with AMTI and 12 mat- ched healthy individuals. Questionnaires about sleep and cognition as well as polysomnography （PSG） were performed on days 14 and 90 post-stroke. Compared to heal- thy controls, in patients with AMTI, hyposomnia was more prevalent; sleep architecture was disrupted as indicated by decreased sleep efficiency, increased sleep latency, and decreased non-rapid eye movement sleep stages 2 and 3; more sleep-related breathing disorders occurred; and cog- nitive functions were worse, especially memory. While sleep apnea and long-delay memory recovered to a large extent in the patients, other sleep and cognitive function deficit often persisted. Patients with AMTI are at an increased risk for hyposomnia, sleep structure disturbance, sleep apnea, and memory deficits. Although these abnormalities improved over time, the slow and incomplete improvement suggest that early management should be considered in these patients.展开更多
Purpose:Thalamic hemorrhage breaking into ventricles(THBIV)is a devastating disease with high morbidity and mortality rates.Endoscopic surgery(ES)may improve outcomes,although there is no consensus on its superiority....Purpose:Thalamic hemorrhage breaking into ventricles(THBIV)is a devastating disease with high morbidity and mortality rates.Endoscopic surgery(ES)may improve outcomes,although there is no consensus on its superiority.We investigated the efficacy and safety of ES and compared the outcomes of different management strategies by ES,hematoma puncture and drainage(HPD),and external ventricular drainage(EVD)in patients with THBIV.Methods:We retrospectively analyzed patients with THBIV treated by ES,HPD,or EVD at our hospital from June 2015 to June 2018.Patients were categorized into anteromedial and posterolateral groups based on THBIV location,and then the two groups were further divided into ES,HPD,and EVD subgroups.Individualized surgical approach was adopted according to the location of the hematoma in the ES subgroups.Patient characteristics and surgical outcomes were investigated.Results:We analyzed 211 consecutive patients.There were no significant differences in clinical characteristics or incidence of perioperative procedure-related complications(postoperative rebleeding and intracranial infection)in either anteromedial or posterolateral groups.Compared with other therapeutic methods,the ES subgroups had the highest hematoma evacuation rate,shortest drainage time,and lowest incidence of chronic ventricular dilatation(all p<0.05).Among the three anteromedial subgroups,ES subgroup had the best clinical outcomes which was assessed by the modified Rankin Scale,followed by HPD and EVD subgroups(p<0.01);while in the posterolateral subgroups,clinical outcomes in the ES and HPD subgroups were similar and better than that in the EVD subgroup(p=0.037).Conclusion:Individualized surgical ES approach for removal of thalamic and ventricular hematomas is a minimally invasive,safe,and effective strategy for the treatment of THBIV with a thalamic hematoma volume of 10-30 mL.展开更多
Objective To explore predictors of the 6-month clinical outcome ofthalamic hemorrhage, and evaluate if minimally invasive thalamic hematoma drainage （THD） could improve its prognosis. Methods A total of 54 patients ...Objective To explore predictors of the 6-month clinical outcome ofthalamic hemorrhage, and evaluate if minimally invasive thalamic hematoma drainage （THD） could improve its prognosis. Methods A total of 54 patients with spontaneous thalamic hemorrhage were evaluated retrospectively. Clinical data, including demographics, stroke risk factors, neuroimaging variables, Glasgow Coma Score （GCS） on admission, surgical strategy, and outcome, were collected. Clinical outcome was assessed using a modified Rankin Scale, six months after onset. Univariate analysis and multivariate logistic regression analysis were performed to determine predictors of a poor outcome. Results Conservative treatnaent was performed for five patients （9.3%）, external ventricular drainage （EVD） for 20 patients （37.0%）, THD for four patients （7.4%）, and EVD combined with THD for 25 patients （46.3%）. At six months after onset, 21 （38.9%） patients achieved a favorable outcome, while 33 （61.1%） had a poor outcome. In the univariate analysis, predictors of poor 6-month outcome were lower GCS on admis- sion （P = 0.001）, larger hematoma volume （P 〈 0.001）, midline shift （P = 0.035）, acute hydrocephalus （P = 0.039）, and no THD （P = 0.037）. The independent predictors of poor outcome, according to the multivariate logistic regression analysis, were no THD and larger hematoma volume. Conclusions Minimally invasive THD, which removes most of the hematoma within a few days, with limited damage to perihematomal brain tissue, improved the 6-month outcome of thalamic hemorrhage. Thus, THD can be widely applied to treat patients with thalamic hemorrhage.展开更多
Background：Recent clinical and preclinical studies have suggested that deep brain stimulation （DBS） can be used as a tool to enhance cognitive functions.The aim of the present study was to investigate the impact of...Background：Recent clinical and preclinical studies have suggested that deep brain stimulation （DBS） can be used as a tool to enhance cognitive functions.The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit,including the anterior nucleus of thalamus （ANT）,the entorhinal cortex （EC）,and the fornix （FX）,on cognitive behaviors in an Alzheimer＇s disease （AD） rat model.Methods：Forty-eight rats were subjected to an intrahippocampal injection ofamyloid peptides 1-42 to induce an AD model.Rats were divided into six groups：DBS and sham DBS groups of ANT,EC,and FX.Spatial learning and memory were assessed by the Morris water maze （MWM）.Recognition memory was investigated by the novel object recognition memory test （NORM）.Locomotor and anxiety-related behaviors were detected by the open field test （OF）.By using two-way analysis of variance （ANOVA）,behavior differences between the six groups were analyzed.Results：In the MWM,the ANT,EC,and FX DBS groups performed differently in terms of the time spent in the platform zone （F（2.23） =6.04,P ＜ 0.01）,the frequency of platform crossing （F（2,23） =11.53,P ＜ 0.001）,and the percent time spent within the platform quadrant （F（2,23） =6.29,P ＜ 0.01）.In the NORM,the EC and FX DBS groups spent more time with the novel object,although the ANT DBS group did not （F（2,23） =10.03,P ＜ 0.001）.In the OF,all of the groups showed a similar total distance moved （F（1.42） =1.14,P =0.29）and relative time spent in the center （F（2,42） =0.56,P =0.58）.Conclusions：Our results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently thanANT DBS.In addition,hippocampus-independent recognition memory was enhanced by EC and FX DBS.None of the targets showed side-effects of anxiety or locomotor behaviors.展开更多
Background：The antiepileptic effect of the anterior thalamic nuclei （ANT） stimulation has been demonstrated;however,its underlying mechanism remains unclear.The aim of this study was to investigate the effect of ch...Background：The antiepileptic effect of the anterior thalamic nuclei （ANT） stimulation has been demonstrated;however,its underlying mechanism remains unclear.The aim of this study was to investigate the effect of chronic ANT stimulation on hippocampal neuron loss and apoptosis.Methods：Sixty-four rats were divided into four groups：The control group,the kainic acid （KA） group,the sham-deep brain stimulation （DBS） group,and the DBS group.KA was used to induce epilepsy.Seizure count and latency to the first spontaneous seizures were calculated.Nissl staining was used to analyze hippocampal neuronal loss.Polymerase chain reaction and Western blotting were conducted to assess the expression of caspase-3 （Casp3）,B-cell lymphoma-2 （Bcl2）,and Bcl2-associated X protein （Box） in the hippocampal CA3 region.One-way analysis of variance was used to determine the differences between the four groups.Results：The latency to the first spontaneous seizures in the DBS group was significantly longer than that in the KA group （27.50 ± 8.05 vs.16.38 ± 7.25 days,P =0.0005）.The total seizure number in the DBS group was also significantly reduced （DBS vs.KA group：11.75 ± 6.80 vs.23.25 ± 7.72,P =0.0002）.Chronic ANT-DBS reduced neuronal loss in the hippocampal CA3 region （DBS vs.KA group：23.58 ± 6.34 vs.13.13 ± 4.00,P =0.0012）.After chronic DBS,the relative mRNA expression level of Casp3 was decreased （DBS vs.KA group：1.18 ± 0.37 vs.2.09 ± 0.46,P =0.0003）,and the relative mRNA expression level of Bcl2 was increased （DBS vs.KA group：0.92 ± 0.21 vs.0.48 ± 0.16,P =0.0004）.The protein expression levels of CASP3 （DBS vs.KA group：1.25 ± 0.26 vs.2.49 ± 0.38,P 〈 0.0001） and BAX （DBS vs.KA group：1.57 ± 0.49 vs.2.80 ± 0.63,P =0.0012） both declined in the DBS group whereas the protein expression level of BCL2 （DBS vs.KA group：0.78 ± 0.32 vs.0.36 ± 0.17,P =0.0086） increased in the DBS group.Conclusions：This study demonstrated that chronic ANT stimulation cou展开更多
The thalamostriatal pathway is implicated in Parkinson's disease(PD); however, PD-related changes in the relationship between oscillatory activity in the centromedian-parafascicular complex(CM/Pf, or the Pf in rod...The thalamostriatal pathway is implicated in Parkinson's disease(PD); however, PD-related changes in the relationship between oscillatory activity in the centromedian-parafascicular complex(CM/Pf, or the Pf in rodents) and the dorsal striatum(DS) remain unclear.Therefore, we simultaneously recorded local field potentials(LFPs) in both the Pf and DS of hemiparkinsonian and control rats during epochs of rest or treadmill walking. The dopamine-lesioned rats showed increased LFP power in the beta band(12 Hz–35 Hz) in the Pf and DS during both epochs, but decreased LFP power in the delta(0.5 Hz–3 Hz) band in the Pf during rest epochs and in the DS during both epochs, compared to control rats. In addition,exaggerated low gamma(35 Hz–70 Hz) oscillations after dopamine loss were restricted to the Pf regardless of the behavioral state. Furthermore, enhanced synchronization of LFP oscillations was found between the Pf and DS after the dopamine lesion. Significant increases occurred in the mean coherence in both theta(3 Hz–7 Hz) and beta bands,and a significant increase was also noted in the phase coherence in the beta band between the Pf and DS during rest epochs. During the treadmill walking epochs, significant increases were found in both the alpha(7 Hz–12 Hz)and beta bands for two coherence measures. Collectively,dramatic changes in the relative LFP power and coherence in the thalamostriatal pathway may underlie the dysfunction of the basal ganglia-thalamocortical network circuits in PD, contributing to some of the motor and non-motor symptoms of the disease.展开更多
BACKGROUND Stress-induced gastric ulcer(SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress(RWIS) can cause serious gastrointestinal dysfunction and has been widely use...BACKGROUND Stress-induced gastric ulcer(SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress(RWIS) can cause serious gastrointestinal dysfunction and has been widely used to study the pathogenesis of SGU to identify medications that can cure the disease. The mediodorsal thalamic nucleus(MD) is the centre integrating visceral and physical activity and contributes to SGU induced by RWIS. Hence, the role of the MD during RWIS needs to be studied.AIM To screen for differentially expressed proteins in the MD of the RWIS rats to further elucidate molecular mechanisms of SGU.METHODS Male Wistar rats were selected randomly and divided into two groups, namely, a control group and an RWIS group. Gastric mucosal lesions of the sacrificed rats were measured using the erosion index and the proteomic profiles of the MD were generated through isobaric tags for relative and absolute quantitation(iTRAQ) coupled with two-dimensional liquid chromatography and tandem mass spectrometry. Additionally, iTRAQ results were verified by Western blot analysis.RESULTS A total of 2853 proteins were identified, and these included 65 dysregulated(31 upregulated and 34 downregulated) proteins(fold change ratio ≥ 1.2). Gene Ontology(GO) analysis showed that most of the upregulated proteins are primarily related to cell division, whereas most of the downregulated proteins are related to neuron morphogenesis and neurotransmitter regulation. Ingenuity Pathway Analysis revealed that the dysregulated proteins are mainly involved in the neurological disease signalling pathways. Furthermore, our results indicated that glycogen synthase kinase-3 beta might be related to the central mechanismthrough which RWIS gives rise to SGU.CONCLUSION Quantitative proteomic analysis elucidated the molecular targets associated with the production of SGU and provides insights into the role of the MD. The underlying molecular mechanisms need to be further dissected.展开更多
The α2δ-1 subunit of the voltage-gated Ca2＋ channel （VGCC） is a molecular target of gabapentin （GBP）, which has been used as a first-line drug for the relief of neuropathic pain. GBP exerts its anti-nociceptive...The α2δ-1 subunit of the voltage-gated Ca2＋ channel （VGCC） is a molecular target of gabapentin （GBP）, which has been used as a first-line drug for the relief of neuropathic pain. GBP exerts its anti-nociceptive effects by disrupting trafficking of the α2δ-1 subunit to the presynaptic membrane, resulting in decreased neurotrans- mitter release. We previously showed that GBP has an anti- allodynic effect in the first two weeks; but this is followed by insensitivity in the later stage after repeated adminis- tration in a rat model of central post-stroke pain （CPSP） hypersensitivity induced by intra-thalamic hemorrhage. To explore the mechanisms underlying GBP insensitivity, the cellular localization and time-course of expression of the α2δ-1 subunit in both the thalamus and spinal dorsal horn were studied in the same model. We found that the α2δ-1 subunit was mostly localized in neurons, but not astrocytes and microglia. The level of α2δ-1 protein increased in the first two weeks after injury but then decreased in the third week, when GBP insensitivity occurred. Furthermore, the c^2g-1 down-regulation was likely caused by later neuronal loss in the injured thalamus through a mechanism other than apoptosis. In summary, the present results suggest that the GBP receptor ~2^-1 is mainly expressed in thalamic neurons in which it is up-regulated in the early stage of CPSP but this is followed by dramatic down-regulation, which is likely associated with GBP insensitivity after long-term use.展开更多
Current research on the various forms of autoscopic phenomena addresses the clinical and neurological correlates of out-of-body experiences, autoscopic hallucinations, and heautoscopy. Yet most of this research is bas...Current research on the various forms of autoscopic phenomena addresses the clinical and neurological correlates of out-of-body experiences, autoscopic hallucinations, and heautoscopy. Yet most of this research is based on functional magnetic resonance imaging results and focuses predominantly on abnormal cortical activity. Previously we proposed that visual consciousness resulted from the dynamic retinogeniculo-cortical oscillations, such that the photoreceptors dynamically integrated with visual and other vision-associated cortices, and was theorized to be mapped out by photoreceptor discs and rich retinal networks which synchronized with the retinotopic mapping and the associated cortex. The feedback from neural input that is received from the thalamus and cortex via retinogeniculo-cortical oscillations and sent to the retina is multifold higher than feed-forward input to the cortex. This can effectively translate into out-of-body experiences projected onto the screen formed by the retina as it is perceived via feedback and feed-forward oscillations from the reticular thalamic nucleus, or “internal searchlight”. This article explores the role of the reticular thalamic nucleus and the retinogeniculo-cortical oscillations as pivotal internal components in vision and various autoscopic phenomena.展开更多
The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease.However,the exact role of the mediodorsal thalamic nucleus in the function of the p...The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease.However,the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear.To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex,a model of Parkinson’s disease was established by injecting 8μg 6-hydroxydopamine into the substantia nigra compacta of rats.After 1 or 3 weeks,0.3μg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain.At 3 or 5 weeks after the initial injury,neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically.The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining.Results demonstrated that after injury,the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats.Compared with normal medial prefrontal cortical neurons,at 3 and 5 weeks after substantia nigra compacta injury,the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge,with an increased discharge interval.The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge,but the discharge interval was only higher at 3 weeks.At 3 weeks after the combined lesions,the discharge frequency,discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex.These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex.The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefron展开更多
Background Although thalamotomy could dramatically improve both parkinsonian resting tremor and essential tremor （ET）, the mechanisms are obviously different. This study aimed to investigate the neuronal activities ...Background Although thalamotomy could dramatically improve both parkinsonian resting tremor and essential tremor （ET）, the mechanisms are obviously different. This study aimed to investigate the neuronal activities in the ventrolateral thalamus of Parkinson＇s disease （PD） and ET. Methods Thirty-six patients （PD： 20, ET： 16） were studied. Microelectrode recordings in the ventral oral posterior （Vop）and the ventral intermediate nucleus （Vim） of thalamus was performed on these patients who underwent thalamotomy.Electromyography （EMG） was recorded simultaneously on the contralateral limbs to surgery. Single unit analysis and the interspike intervals （ISIs） were measured for each neuronal type. ISI histogram and auto-correlograms were constructed to estimate the pattern of neuronal firing. Mann-Whitney test and Kruskal-Wallis （K-W） test were used to compare the mean spontaneous firing rate （MSFR） of neurons of PD and ET patients. Results Three hundred and twenty-three neurons were obtained from 20 PD trajectories, including 151 （46.7%） tremor related neuronal activity, 74 neurons （22.9%） with tonic firing, and 98 （30.4%） neurons with irregular discharge. One hundred and eighty-seven neurons were identified from 16 ET trajectories including 46 （24.6%） tremor-related neuronal activity, 77 （41.2%） neurons with tonic firing, and 64 neurons （34.2%） with irregular discharge. The analysis of MSFR of neurons with tonic firing was 26.7 （3.4-68.3） Hz （n=74） and that of neurons with irregular discharge （n=98） was 13.9 （3.0-58.1） Hz in PD; whereas MSFR of neurons with tonic firing （n=77） was 48.8 （19.0-135.5） Hz and that of neurons with irregular discharge （n=64） was 26.3 （8.7-84.7） Hz in ET. There were significant differences in the MSFR of two types of neuron for PD and ET （K-W test, both P〈0.05）. Significant differences in the MSFR of neuron were also obtained from Vop and Vim of PD and ET （16.3 Hz vs. 34.8 Hz, 28.0 Hz vs.展开更多
BACKGROUND：Glutamate acid ionotropic receptor N-methyl-D-aspartic acid （NMDA） takes part in long-term potentiation, thereby influencing the process of learning and memory. OBJECTIVE： To verify expression of NMDA 2...BACKGROUND：Glutamate acid ionotropic receptor N-methyl-D-aspartic acid （NMDA） takes part in long-term potentiation, thereby influencing the process of learning and memory. OBJECTIVE： To verify expression of NMDA 2A/B and 2B receptors in the anterior thalamic nucleus and subiculum complex of rats. DESIGN, TIME AND SETTING： A single-sample observation was performed at Department of Anatomy in Dalian Medical University （Dalian, Liaoning, China） from April to September in 2007. MATERIALS： Ten adult Wistar rats were used for this study, as well as rabbit anti-NMDA 2A/B and 2B antibodies. METHODS： The rats were anesthetized and perfused, followed by brain resection and coronal sectioning of the brain tissue. A 1：3 series was selected for immunohistochemistry, using antibodies specific to NMDA 2A/B and 2B receptors. Photos were taken using the Nikon image analysis system. MAIN OUTCOME MEASURES： Expression and distribution of immunohistochemistry staining of NMDA 2A/B and 2B receptor subunits. RESULTS： There were a large number of NMDA 2A/B and 2B receptor-positive neurons distributed throughout the anterior dorsal thalamic nucleus. In the anterior ventral thalamic nucleus, distribution of positive neurons was rare, staining intensity was lighter, and cell bodies were smaller compared with the anterior dorsal thalamic nucleus. In the subiculum complex, staining intensity of NMDA 2A/B and 2B-positive neurons was weakest in the molecular layer and stronger in the pyramidal layer, in particular the region with large cell bodies adjacent to the molecular layer. In the multiform layer, more positive neurons of various sizes were detected. CONCLUSION： NMDA 2A/B and 2B receptor subunits were richly distributed in the anterior thalamic nucleus, with a small difference existing between the anterior dorsal nucleus and anterior ventral nucleus. These neurons were also differentially distributed within the three layers of the subiculum complex.展开更多
基金supported by the Health Industry Key Research Project of Tianjin Municipality,China(12KG132)the Science and Technology Plan Project of Tianjin Municipality,China(13ZCZDSY01900)
文摘In order to characterize sleep and the cognitive patterns in patients with acute minor thalamic infarction （AMTI）, we enrolled 27 patients with AMTI and 12 mat- ched healthy individuals. Questionnaires about sleep and cognition as well as polysomnography （PSG） were performed on days 14 and 90 post-stroke. Compared to heal- thy controls, in patients with AMTI, hyposomnia was more prevalent; sleep architecture was disrupted as indicated by decreased sleep efficiency, increased sleep latency, and decreased non-rapid eye movement sleep stages 2 and 3; more sleep-related breathing disorders occurred; and cog- nitive functions were worse, especially memory. While sleep apnea and long-delay memory recovered to a large extent in the patients, other sleep and cognitive function deficit often persisted. Patients with AMTI are at an increased risk for hyposomnia, sleep structure disturbance, sleep apnea, and memory deficits. Although these abnormalities improved over time, the slow and incomplete improvement suggest that early management should be considered in these patients.
文摘Purpose:Thalamic hemorrhage breaking into ventricles(THBIV)is a devastating disease with high morbidity and mortality rates.Endoscopic surgery(ES)may improve outcomes,although there is no consensus on its superiority.We investigated the efficacy and safety of ES and compared the outcomes of different management strategies by ES,hematoma puncture and drainage(HPD),and external ventricular drainage(EVD)in patients with THBIV.Methods:We retrospectively analyzed patients with THBIV treated by ES,HPD,or EVD at our hospital from June 2015 to June 2018.Patients were categorized into anteromedial and posterolateral groups based on THBIV location,and then the two groups were further divided into ES,HPD,and EVD subgroups.Individualized surgical approach was adopted according to the location of the hematoma in the ES subgroups.Patient characteristics and surgical outcomes were investigated.Results:We analyzed 211 consecutive patients.There were no significant differences in clinical characteristics or incidence of perioperative procedure-related complications(postoperative rebleeding and intracranial infection)in either anteromedial or posterolateral groups.Compared with other therapeutic methods,the ES subgroups had the highest hematoma evacuation rate,shortest drainage time,and lowest incidence of chronic ventricular dilatation(all p<0.05).Among the three anteromedial subgroups,ES subgroup had the best clinical outcomes which was assessed by the modified Rankin Scale,followed by HPD and EVD subgroups(p<0.01);while in the posterolateral subgroups,clinical outcomes in the ES and HPD subgroups were similar and better than that in the EVD subgroup(p=0.037).Conclusion:Individualized surgical ES approach for removal of thalamic and ventricular hematomas is a minimally invasive,safe,and effective strategy for the treatment of THBIV with a thalamic hematoma volume of 10-30 mL.
基金This study was supported by National Natural Science Foundation of China （81501054）, and Kejihuimin Project of Shandong Province （2014kjhm0101）.
文摘Objective To explore predictors of the 6-month clinical outcome ofthalamic hemorrhage, and evaluate if minimally invasive thalamic hematoma drainage （THD） could improve its prognosis. Methods A total of 54 patients with spontaneous thalamic hemorrhage were evaluated retrospectively. Clinical data, including demographics, stroke risk factors, neuroimaging variables, Glasgow Coma Score （GCS） on admission, surgical strategy, and outcome, were collected. Clinical outcome was assessed using a modified Rankin Scale, six months after onset. Univariate analysis and multivariate logistic regression analysis were performed to determine predictors of a poor outcome. Results Conservative treatnaent was performed for five patients （9.3%）, external ventricular drainage （EVD） for 20 patients （37.0%）, THD for four patients （7.4%）, and EVD combined with THD for 25 patients （46.3%）. At six months after onset, 21 （38.9%） patients achieved a favorable outcome, while 33 （61.1%） had a poor outcome. In the univariate analysis, predictors of poor 6-month outcome were lower GCS on admis- sion （P = 0.001）, larger hematoma volume （P 〈 0.001）, midline shift （P = 0.035）, acute hydrocephalus （P = 0.039）, and no THD （P = 0.037）. The independent predictors of poor outcome, according to the multivariate logistic regression analysis, were no THD and larger hematoma volume. Conclusions Minimally invasive THD, which removes most of the hematoma within a few days, with limited damage to perihematomal brain tissue, improved the 6-month outcome of thalamic hemorrhage. Thus, THD can be widely applied to treat patients with thalamic hemorrhage.
基金This study was supported by grants from the National Natural Science Foundation of China，the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding，the Scientific Research Common Program of Beijing Municipal Commission of Education （No.KZ201510025029）.Conflict of Interest：None declared
文摘Background：Recent clinical and preclinical studies have suggested that deep brain stimulation （DBS） can be used as a tool to enhance cognitive functions.The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit,including the anterior nucleus of thalamus （ANT）,the entorhinal cortex （EC）,and the fornix （FX）,on cognitive behaviors in an Alzheimer＇s disease （AD） rat model.Methods：Forty-eight rats were subjected to an intrahippocampal injection ofamyloid peptides 1-42 to induce an AD model.Rats were divided into six groups：DBS and sham DBS groups of ANT,EC,and FX.Spatial learning and memory were assessed by the Morris water maze （MWM）.Recognition memory was investigated by the novel object recognition memory test （NORM）.Locomotor and anxiety-related behaviors were detected by the open field test （OF）.By using two-way analysis of variance （ANOVA）,behavior differences between the six groups were analyzed.Results：In the MWM,the ANT,EC,and FX DBS groups performed differently in terms of the time spent in the platform zone （F（2.23） =6.04,P ＜ 0.01）,the frequency of platform crossing （F（2,23） =11.53,P ＜ 0.001）,and the percent time spent within the platform quadrant （F（2,23） =6.29,P ＜ 0.01）.In the NORM,the EC and FX DBS groups spent more time with the novel object,although the ANT DBS group did not （F（2,23） =10.03,P ＜ 0.001）.In the OF,all of the groups showed a similar total distance moved （F（1.42） =1.14,P =0.29）and relative time spent in the center （F（2,42） =0.56,P =0.58）.Conclusions：Our results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently thanANT DBS.In addition,hippocampus-independent recognition memory was enhanced by EC and FX DBS.None of the targets showed side-effects of anxiety or locomotor behaviors.
基金This study was supported by grants from the National Natural Science Foundation of China，the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding
文摘Background：The antiepileptic effect of the anterior thalamic nuclei （ANT） stimulation has been demonstrated;however,its underlying mechanism remains unclear.The aim of this study was to investigate the effect of chronic ANT stimulation on hippocampal neuron loss and apoptosis.Methods：Sixty-four rats were divided into four groups：The control group,the kainic acid （KA） group,the sham-deep brain stimulation （DBS） group,and the DBS group.KA was used to induce epilepsy.Seizure count and latency to the first spontaneous seizures were calculated.Nissl staining was used to analyze hippocampal neuronal loss.Polymerase chain reaction and Western blotting were conducted to assess the expression of caspase-3 （Casp3）,B-cell lymphoma-2 （Bcl2）,and Bcl2-associated X protein （Box） in the hippocampal CA3 region.One-way analysis of variance was used to determine the differences between the four groups.Results：The latency to the first spontaneous seizures in the DBS group was significantly longer than that in the KA group （27.50 ± 8.05 vs.16.38 ± 7.25 days,P =0.0005）.The total seizure number in the DBS group was also significantly reduced （DBS vs.KA group：11.75 ± 6.80 vs.23.25 ± 7.72,P =0.0002）.Chronic ANT-DBS reduced neuronal loss in the hippocampal CA3 region （DBS vs.KA group：23.58 ± 6.34 vs.13.13 ± 4.00,P =0.0012）.After chronic DBS,the relative mRNA expression level of Casp3 was decreased （DBS vs.KA group：1.18 ± 0.37 vs.2.09 ± 0.46,P =0.0003）,and the relative mRNA expression level of Bcl2 was increased （DBS vs.KA group：0.92 ± 0.21 vs.0.48 ± 0.16,P =0.0004）.The protein expression levels of CASP3 （DBS vs.KA group：1.25 ± 0.26 vs.2.49 ± 0.38,P 〈 0.0001） and BAX （DBS vs.KA group：1.57 ± 0.49 vs.2.80 ± 0.63,P =0.0012） both declined in the DBS group whereas the protein expression level of BCL2 （DBS vs.KA group：0.78 ± 0.32 vs.0.36 ± 0.17,P =0.0086） increased in the DBS group.Conclusions：This study demonstrated that chronic ANT stimulation cou
基金supported by the Science Technological Project of Shandong Province (2018CXGC1502 and 2016GSF201058)the National Natural Science Foundation of China (31571104 and 81501149)
文摘The thalamostriatal pathway is implicated in Parkinson's disease(PD); however, PD-related changes in the relationship between oscillatory activity in the centromedian-parafascicular complex(CM/Pf, or the Pf in rodents) and the dorsal striatum(DS) remain unclear.Therefore, we simultaneously recorded local field potentials(LFPs) in both the Pf and DS of hemiparkinsonian and control rats during epochs of rest or treadmill walking. The dopamine-lesioned rats showed increased LFP power in the beta band(12 Hz–35 Hz) in the Pf and DS during both epochs, but decreased LFP power in the delta(0.5 Hz–3 Hz) band in the Pf during rest epochs and in the DS during both epochs, compared to control rats. In addition,exaggerated low gamma(35 Hz–70 Hz) oscillations after dopamine loss were restricted to the Pf regardless of the behavioral state. Furthermore, enhanced synchronization of LFP oscillations was found between the Pf and DS after the dopamine lesion. Significant increases occurred in the mean coherence in both theta(3 Hz–7 Hz) and beta bands,and a significant increase was also noted in the phase coherence in the beta band between the Pf and DS during rest epochs. During the treadmill walking epochs, significant increases were found in both the alpha(7 Hz–12 Hz)and beta bands for two coherence measures. Collectively,dramatic changes in the relative LFP power and coherence in the thalamostriatal pathway may underlie the dysfunction of the basal ganglia-thalamocortical network circuits in PD, contributing to some of the motor and non-motor symptoms of the disease.
基金Supported by National Natural Science Foundation of China,No.31501861Natural Science Foundation of Shandong Province,China,No.ZR2015CM013
文摘BACKGROUND Stress-induced gastric ulcer(SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress(RWIS) can cause serious gastrointestinal dysfunction and has been widely used to study the pathogenesis of SGU to identify medications that can cure the disease. The mediodorsal thalamic nucleus(MD) is the centre integrating visceral and physical activity and contributes to SGU induced by RWIS. Hence, the role of the MD during RWIS needs to be studied.AIM To screen for differentially expressed proteins in the MD of the RWIS rats to further elucidate molecular mechanisms of SGU.METHODS Male Wistar rats were selected randomly and divided into two groups, namely, a control group and an RWIS group. Gastric mucosal lesions of the sacrificed rats were measured using the erosion index and the proteomic profiles of the MD were generated through isobaric tags for relative and absolute quantitation(iTRAQ) coupled with two-dimensional liquid chromatography and tandem mass spectrometry. Additionally, iTRAQ results were verified by Western blot analysis.RESULTS A total of 2853 proteins were identified, and these included 65 dysregulated(31 upregulated and 34 downregulated) proteins(fold change ratio ≥ 1.2). Gene Ontology(GO) analysis showed that most of the upregulated proteins are primarily related to cell division, whereas most of the downregulated proteins are related to neuron morphogenesis and neurotransmitter regulation. Ingenuity Pathway Analysis revealed that the dysregulated proteins are mainly involved in the neurological disease signalling pathways. Furthermore, our results indicated that glycogen synthase kinase-3 beta might be related to the central mechanismthrough which RWIS gives rise to SGU.CONCLUSION Quantitative proteomic analysis elucidated the molecular targets associated with the production of SGU and provides insights into the role of the MD. The underlying molecular mechanisms need to be further dissected.
基金supported by the National Natural Science Foundation of China(81171049)the National Basic Research Development Program of China(2011CB504100 and2013CB835100)+1 种基金the National Key Technology R&D Program of China(2013BAI04B04)the Twelfth Five-Year Project of China(AWS12J004)
文摘The α2δ-1 subunit of the voltage-gated Ca2＋ channel （VGCC） is a molecular target of gabapentin （GBP）, which has been used as a first-line drug for the relief of neuropathic pain. GBP exerts its anti-nociceptive effects by disrupting trafficking of the α2δ-1 subunit to the presynaptic membrane, resulting in decreased neurotrans- mitter release. We previously showed that GBP has an anti- allodynic effect in the first two weeks; but this is followed by insensitivity in the later stage after repeated adminis- tration in a rat model of central post-stroke pain （CPSP） hypersensitivity induced by intra-thalamic hemorrhage. To explore the mechanisms underlying GBP insensitivity, the cellular localization and time-course of expression of the α2δ-1 subunit in both the thalamus and spinal dorsal horn were studied in the same model. We found that the α2δ-1 subunit was mostly localized in neurons, but not astrocytes and microglia. The level of α2δ-1 protein increased in the first two weeks after injury but then decreased in the third week, when GBP insensitivity occurred. Furthermore, the c^2g-1 down-regulation was likely caused by later neuronal loss in the injured thalamus through a mechanism other than apoptosis. In summary, the present results suggest that the GBP receptor ~2^-1 is mainly expressed in thalamic neurons in which it is up-regulated in the early stage of CPSP but this is followed by dramatic down-regulation, which is likely associated with GBP insensitivity after long-term use.
文摘Current research on the various forms of autoscopic phenomena addresses the clinical and neurological correlates of out-of-body experiences, autoscopic hallucinations, and heautoscopy. Yet most of this research is based on functional magnetic resonance imaging results and focuses predominantly on abnormal cortical activity. Previously we proposed that visual consciousness resulted from the dynamic retinogeniculo-cortical oscillations, such that the photoreceptors dynamically integrated with visual and other vision-associated cortices, and was theorized to be mapped out by photoreceptor discs and rich retinal networks which synchronized with the retinotopic mapping and the associated cortex. The feedback from neural input that is received from the thalamus and cortex via retinogeniculo-cortical oscillations and sent to the retina is multifold higher than feed-forward input to the cortex. This can effectively translate into out-of-body experiences projected onto the screen formed by the retina as it is perceived via feedback and feed-forward oscillations from the reticular thalamic nucleus, or “internal searchlight”. This article explores the role of the reticular thalamic nucleus and the retinogeniculo-cortical oscillations as pivotal internal components in vision and various autoscopic phenomena.
基金supported by the Key Research Project of Science and Technology of Henan Province of China,No.14B180007(to LLF)the Development Project of Science and Technology of Luoyang Municipality of China,No.1401087A-5(to LLF)
文摘The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease.However,the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear.To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex,a model of Parkinson’s disease was established by injecting 8μg 6-hydroxydopamine into the substantia nigra compacta of rats.After 1 or 3 weeks,0.3μg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain.At 3 or 5 weeks after the initial injury,neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically.The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining.Results demonstrated that after injury,the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats.Compared with normal medial prefrontal cortical neurons,at 3 and 5 weeks after substantia nigra compacta injury,the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge,with an increased discharge interval.The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge,but the discharge interval was only higher at 3 weeks.At 3 weeks after the combined lesions,the discharge frequency,discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex.These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex.The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefron
基金The study was supported by grants from National Natural Science Foundation of China （No. 30370473 and No. 30770746）. We would like to thank Drs. HU Yong-sheng, ZHU Hong-wei, TAO Wei, YU Tao, MA Kai, YAN Xiao-ming, ZHANG Xiao-hua and CAI Li-xin who provide assistance to the study.
文摘Background Although thalamotomy could dramatically improve both parkinsonian resting tremor and essential tremor （ET）, the mechanisms are obviously different. This study aimed to investigate the neuronal activities in the ventrolateral thalamus of Parkinson＇s disease （PD） and ET. Methods Thirty-six patients （PD： 20, ET： 16） were studied. Microelectrode recordings in the ventral oral posterior （Vop）and the ventral intermediate nucleus （Vim） of thalamus was performed on these patients who underwent thalamotomy.Electromyography （EMG） was recorded simultaneously on the contralateral limbs to surgery. Single unit analysis and the interspike intervals （ISIs） were measured for each neuronal type. ISI histogram and auto-correlograms were constructed to estimate the pattern of neuronal firing. Mann-Whitney test and Kruskal-Wallis （K-W） test were used to compare the mean spontaneous firing rate （MSFR） of neurons of PD and ET patients. Results Three hundred and twenty-three neurons were obtained from 20 PD trajectories, including 151 （46.7%） tremor related neuronal activity, 74 neurons （22.9%） with tonic firing, and 98 （30.4%） neurons with irregular discharge. One hundred and eighty-seven neurons were identified from 16 ET trajectories including 46 （24.6%） tremor-related neuronal activity, 77 （41.2%） neurons with tonic firing, and 64 neurons （34.2%） with irregular discharge. The analysis of MSFR of neurons with tonic firing was 26.7 （3.4-68.3） Hz （n=74） and that of neurons with irregular discharge （n=98） was 13.9 （3.0-58.1） Hz in PD; whereas MSFR of neurons with tonic firing （n=77） was 48.8 （19.0-135.5） Hz and that of neurons with irregular discharge （n=64） was 26.3 （8.7-84.7） Hz in ET. There were significant differences in the MSFR of two types of neuron for PD and ET （K-W test, both P〈0.05）. Significant differences in the MSFR of neuron were also obtained from Vop and Vim of PD and ET （16.3 Hz vs. 34.8 Hz, 28.0 Hz vs.
基金the National Natural Science Foundation of China, No. 30470551a Category Project of the Education Department of Liaoning Province, No. 05L1021
文摘BACKGROUND：Glutamate acid ionotropic receptor N-methyl-D-aspartic acid （NMDA） takes part in long-term potentiation, thereby influencing the process of learning and memory. OBJECTIVE： To verify expression of NMDA 2A/B and 2B receptors in the anterior thalamic nucleus and subiculum complex of rats. DESIGN, TIME AND SETTING： A single-sample observation was performed at Department of Anatomy in Dalian Medical University （Dalian, Liaoning, China） from April to September in 2007. MATERIALS： Ten adult Wistar rats were used for this study, as well as rabbit anti-NMDA 2A/B and 2B antibodies. METHODS： The rats were anesthetized and perfused, followed by brain resection and coronal sectioning of the brain tissue. A 1：3 series was selected for immunohistochemistry, using antibodies specific to NMDA 2A/B and 2B receptors. Photos were taken using the Nikon image analysis system. MAIN OUTCOME MEASURES： Expression and distribution of immunohistochemistry staining of NMDA 2A/B and 2B receptor subunits. RESULTS： There were a large number of NMDA 2A/B and 2B receptor-positive neurons distributed throughout the anterior dorsal thalamic nucleus. In the anterior ventral thalamic nucleus, distribution of positive neurons was rare, staining intensity was lighter, and cell bodies were smaller compared with the anterior dorsal thalamic nucleus. In the subiculum complex, staining intensity of NMDA 2A/B and 2B-positive neurons was weakest in the molecular layer and stronger in the pyramidal layer, in particular the region with large cell bodies adjacent to the molecular layer. In the multiform layer, more positive neurons of various sizes were detected. CONCLUSION： NMDA 2A/B and 2B receptor subunits were richly distributed in the anterior thalamic nucleus, with a small difference existing between the anterior dorsal nucleus and anterior ventral nucleus. These neurons were also differentially distributed within the three layers of the subiculum complex.
