[Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors].

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

[Clinical study of digital six-axis external fixation frame based on CT data for tibiofibular fractures].

Objective: To investigate the clinical effect of applying the digital six-axis external fixation frame based on CT data in the treatment of tibiofibular fractures. Methods: The clinical data of 43 patients with tibiofibular fractures treated by the self-developed digital six-axis external fixation frame based on CT data at Integrated Orthopedic Department of Traditional Chinese Medicine (TCM) and Western Medicine,HongHui Hospital from January 2018 to January 2021 were retrospective analysis.There were 27 males and 16 females,aged (36.0±9.4) years(range:25 to 50 years).AO classification:15 cases of 42A,11 cases of 42B, and 17 cases of 42C.There were 7 open fractures and Gustilo fracture classification:2 cases of type Ⅰ,4 cases of type Ⅱ,and 1 case of type Ⅲ.The two or three plane rings were connected with six connecting rods to form a complete six-axis external fixation frame,and the distal and proximal fracture blocks were connected to the distal and proximal rings by fixation pins,and the lengths of the six connecting rods needed to be adjusted were calculated by using the supporting software according to the CT data after surgery,and then the lengths of the connecting rods were adjusted one by one to complete the reduction of the fracture. The reduction accuracy of this six-axis external fixation brace was evaluated by measuring postoperative radiographs; postoperative recovery and complications were collected,the time of brace removal was recorded,and the function of the affected limb was evaluated according to the Johner-Wruhs score at the final follow-up. Results: Postoperative radiographs showed that all patients achieved satisfactory reduction with lateral displacement(M(IQR)) of 2.3(2.5) mm (range:0.3 to 7.3 mm),anteroposterior displacement of 2.1 (2.4) mm (range:0.3 to 5.7 mm),anteroposterior angulation of 2.5(2.4)°(range:0 to 5°),internal and external angulation of 2.1(1.5)°(range:0 to 4°), and no significant internal or external rotational deformity was detected on the exterior.On the second postoperative day,all patients were able to walk with partial weight-bearing on crutches. All 43 patients were followed up for more than 6 months,with a follow-up period of (33.3±7.3) weeks (range:24 to 42 weeks).The external fixation frame was removed after the fracture healed.The external frame was removed at 20(3)weeks (range:18 to 25 weeks) postoperatively. Up to the final follow up, no secondary fracture occurred in any of them.The Johner-Wruhs score of the affected limb at the last follow-up was excellent in 39 cases and good in 4 cases. Conclusion: The digital six-axis external fixator based on CT data for tibiofibular fractures has the advantages of precise reduction,firm fixation,simple operation,rapid fracture healing,and minimal trauma, which is a minimally invasive method for treating tibiofibular fractures,especially suitable for patients with poor skin and soft tissue conditions such as open injuries.

[Attention should be paid to the treatment of traumatic pancreatitis].

Traumatic pancreatitis(TP) is an acute non-infectious inflammation secondary to pancreatic injury.TP can be masked by analgesia or other organ damage after pancreatic injury. So it is difficult to diagnosis in the early stage, easy to missed and misdiagnosis, subsequently prone to infection of pancreatic necrosis (IPN).At present, the treatment of TP is advocated as a step-by-step treatment strategy, which takes minimally invasive surgery as the guidance and takes into account of the principles of multiple injury treatment, inflammation control, infection and necrosis clearance, which runs through the two important links of pancreatic injury and IPN management.

[Clinicopathological analysis of patients with papillary renal cell carcinoma].

OBJECTIVE: To investigate the clinicopathological features,treatment and prognosis of patients with papillary renal cell carcinoma (PRCC) and PRCC-complicated with tumor thrombus. METHODS: Single center retrospective analysis of 75 patients with PRCC treated from January 2012 to October 2017 was performed. There were 55 males and 20 females at an age range of 24-82 years. Sixteen PRCC patients were complicated with tumor thrombus. All the patients were with a surgery and had clear pathological diagnosis and detailed follow-up data. The clinicopathological features, prognosis and influencing factors of the patients with PRCC and PRCC complicated with tumor thrombus were analyzed and summarized. RESULTS: The average age of the 75 patients was(56.05±11.59)years,the average body mass index (BMI) was (26±3) kg/m², and the average tumor maximum diameter was (5.17±3.85) cm. There were significant differences between tumor maximum diameter larger than 7 cm and less than 7 cm (69.6% vs. 94.4%, P<0.001), lymph node metastasis and no lymph node metastasis (<38% vs. 98%, P<0.001), adrenal metastasis and no adrenal metastasis (0% vs. 95.3%, P<0.001), pulmonary metastasis and no pulmonary metastasis (0% vs.90.7%, P<0.001), complicated with and without tumor thrombus (<66.4% vs. 93.5%, P<0.001) on the effect of 3-year survival rate of the PRCC patients. In this study, there were 16 patients with type 2 PRCC complicated with tumor thrombus. There were significant differences in concomitant symptoms (62.5% vs. 22.0%, P=0.005), maximum tumor diameter (68.8% vs.13.3%, P<0.001), adrenal metastasis (18.8% vs. 0.02%, P=0.029), pulmonary metastasis (18.8% vs. 0%, P=0.008), nuclear grade (P<0.001) and pathological type (100% vs. 44.1%, P<0.001) between the PRCC patients with and without tumor thrombus. CONCLUSION: There were significant differences in tumor diameter,lymph node metastasis,adrenal metastasis, pulmonary metastasis,pathological type, nuclear grade and tumor thrombus in the effect of the 3-year survival rate of PRCC patients. PRCC patients with tumor thrombus were more commonly suffered from type 2 PRCC, for whom the tumor diameter was larger,the nuclear grade was higher,and the distance metastasis happened more easily.

ERCC1 C118T polymorphism has predictive value for platinum-based chemotherapy in patients with late-stage bladder cancer.

This study aims to investigate the association between ERCC1 codon C118T polymorphism and the response rate of platinum-based chemotherapy in patients with late-stage bladder cancer. A total of 41 eligible patients histologically confirmed as having stage IV muscle-invasive transitional cell carcinoma of the bladder were treated with platinum-based chemotherapy for 2-6 cycles. The genotypes of patients were determined by PCR amplification of genomic DNA followed by restriction enzyme digestion. Positive responses were categorized as complete and partial responses. In addition, progression-free survival (PFS) and overall survival (OS) were also determined as indicators of long-term outcomes. The genotype frequencies of C/C, C/T and T/T genotypes were 56.1, 34.1, and 9.8%, respectively. Positive response was observed in 14 patients (34.1%), while 27 patients (65.9%) were negative responders. As compared with individuals carrying the C/T and T/T genotypes, those with the C/C genotype had significantly improved short-term treatment responses (P = 0.018). The median PFS of patients carrying the C/C genotype was 6.3 months, while that of patients with C/T and T/T genotypes was 4.2 months (P = 0.023). Moreover, the median OS for patients carrying the C/C genotype was also longer as compared with that of patients carrying C/T and T/T (11.7 months vs 8.5 months, P = 0.040). Our results indicated that the ERCC1 codon 118 polymorphism may have predictive potential for chemotherapy treatment responses in late-stage bladder cancer patients.

Pattern of relapse following three-field lymphadenectomy of esophageal carcinoma and related factors predictive of recurrence.

PURPOSE: For treatment of esophageal carcinoma, the optimal postoperative radiotherapy target volume after three-field lymph node dissection (3-FLD) had not been determined. We analyzed local recurrence pattern of thoracic esophageal carcinoma and risk factors of lymph node recurrence after 3-FLD without prophylactic radiotherapy. MATERIAL AND METHODS: We reviewed 1282 patients with thoracic esophageal squamous cell carcinoma (ESCC) who were treated with 3-FLD without radiotherapy from 2010 to 2018 and analysed local recurrence patterns and risk factors of lymph node recurrence, in order to provide a reference for determination of the radiotherapy target volume for thoracic ESCC. RESULTS: The lymph node recurrence accounted for 91.0% of treatment failures. The mediastinal, cervical and abdominal lymph node recurrence accounted for 84.92%, 36.07% and 22.30%, respectively (χ2=264.776, P=0.000). The superior, middle and inferior mediastinal lymph node recurrence rates were 67.54%, 27.87% and 0.98%, respectively (χ2=313.600, P=0.000). Cervical metastases were significantly associated with N stage and Preoperative cervical lymph node status. Abdominal metastases were significantly associated with the number of preoperative abdominal lymph node metastases (LNM), tumor location and N stage. CONCLUSIONS: The main pattern of local-regional recurrence might be lymph node metastasis after radical 3-FLD without radiotherapy in esophageal carcinoma. The dangerous lymph node recurrence regions included neck, superior and middle mediastinum. The abdominal areas might be irradiated for lower TEC patients with preoperative abdominal LNM.

[Correlation between alcohol drinking and high risk sexual behaviors in HIV negative clients of female sex workers].

Objective: To explore the correlation between alcohol drinking and high-risk sexual behaviors in HIV negative clients of female sex workers and provide scientific evidence for prevention of HIV sexual transmission. Methods: A cross-sectional survey was conducted in HIV negative clients in Ji'nan and Haikou from December 2018 to May 2019. The estimated sample size was 337, the information about their demographic characteristics, AIDS knowledge awareness, sexual behaviors and alcohol drinking habit were collected through convenience sampling. The data were analyzed by using SPSS 24.0 software. Results: A total of 381 clients were included in this study. Most of them were less than 40 years old, accounting for 89.2% (340/381); 85.3% of them (325/381) reported an education level of high school and above; the clients who were married, had cohabitation with females or had girl friends accounted for 53.2% (202/380). The overall awareness rate of AIDS knowledge was 83.7% (318/380). Of all participants, 80.8% (308/381) had commercial sex in the past year, 79.8% (304/381) had non-commercial sex partners, 62.7% (239/381) had high-risk sexual behaviors. The results of logistic regression showed that compared with those with alcohol drinking frequency ≤2 times per month in last year, the clients with alcohol drinking frequency more than once a week (aOR=3.22, 95%CI: 1.25-8.27) were more likely to have high risk sexual behaviors after adjustment for age, living area, location type of residence, time of local residence, education level, monthly income level, occupation, marital status, knowledge awareness of AIDS and HIV related services, the number of commercial or non-commercial sexual partners in the past year, cost of commercial sex and HIV test frequency. Conclusions: Alcohol drinking is related to high risk sexual behaviors in HIV negative clients, and will increase the risk of HIV transmission. To control AIDS, the intervention of alcohol drinking should be combined with other preventions to improve the correct use of condoms.

Enhancement of inhibitory synaptic transmission in large aspiny neurons after transient cerebral ischemia.

Large aspiny neurons and most of the GABAergic interneurons survive transient cerebral ischemia while medium spiny neurons degenerate in 24 h. Expression of a long-term enhancement of excitatory transmission in medium spiny neurons but not in large aspiny neurons has been indicated to contribute to this selective vulnerability. Because neuronal excitability is determined by the counterbalance of excitation and inhibition, the present study examined inhibitory synaptic transmission in large aspiny neurons after ischemia in rats. Transient cerebral ischemia was induced for 22 min using the four-vessel occlusion method and whole-cell voltage-clamp recording was performed on striatal slices. The amplitudes of evoked inhibitory postsynaptic currents in large aspiny neurons were significantly increased at 3 and 24 h after ischemia, which was mediated by the increase of presynaptic release. Postsynaptic responses were depressed at 24 h after ischemia. Inhibitory postsynaptic currents could be evoked in large aspiny neurons at 24 h after ischemia, suggesting that they receive GABAergic inputs from the survived GABAergic interneurons. Muscimol, a GABA(A) receptor agonist, presynaptically facilitated inhibitory synaptic transmission at 24 h after ischemia. Such facilitation was dependent on the extracellular calcium and voltage-gated sodium channels. The present study demonstrates an enhancement of inhibitory synaptic transmission in large aspiny neurons after ischemia, which might reduce excitotoxicity and contribute, at least in part, to the survival of large aspiny neurons. Our data also suggest that large aspiny neurons might receive inhibitory inputs from GABAergic interneurons.

Role of EGR1 in hippocampal synaptic enhancement induced by tetanic stimulation and amputation.

Hippocampal neurons fire spikes when an animal is at a particular location or performs certain behaviors in a particular place, providing a cellular basis for hippocampal involvement in spatial learning and memory. In a natural environment, spatial memory is often associated with potentially dangerous sensory experiences such as noxious or painful stimuli. The central sites for such pain-associated memory or plasticity have not been identified. Here we present evidence that excitatory glutamatergic synapses within the CA1 region of the hippocampus may play a role in storing pain-related information. Peripheral noxious stimulation induced excitatory postsynaptic potentials (EPSPs) in CA1 pyramidal cells in anesthetized animals. Tissue/nerve injury caused a rapid increase in the level of the immediate-early gene product Egr1 (also called NGFI-A, Krox24, or zif/268) in hippocampal CA1 neurons. In parallel, synaptic potentiation induced by a single tetanic stimulation (100 Hz for 1 s) was enhanced after the injury. This enhancement of synaptic potentiation was absent in mice lacking Egr1. Our data suggest that Egr1 may act as an important regulator of pain-related synaptic plasticity within the hippocampus.

Caffeic acid phenethyl ester prevents cerebellar granule neurons (CGNs) against glutamate-induced neurotoxicity.

Caffeic acid phenethyl ester (CAPE) is an active component of propolis obtained from honeybee hives and is found to have the following properties: anti-mitogenic, anti-carcinogenic, anti-inflammatory, immunomodulatory, and antioxidant. Recent reports suggest that CAPE also has a neuronal protective property against ischemic injury. Since excitotoxicity may play an important role in ischemia, in this study, we investigated whether CAPE could directly protect neurons against excitotoxic insult. We treated cultured rat cerebellar granule neurons (CGNs) with excitotoxic concentrations of glutamate in the presence or absence of CAPE and found that CAPE markedly protected neurons against glutamate-induced neuronal death in a concentration-dependent fashion. Glutamate-induced CGNs death is associated with time-dependent activation of caspase-3 and phosphorylation of p38, both events of which can be blocked by CAPE. Treating CGNs with specific inhibitors of these two enzymes together exerts a synergistic neuroprotective effect, similar to the neuroprotective effect of CAPE exposure. These results suggest that CAPE is able to block glutamate-induced excitotoxicity by inhibiting phosphorylation of p38 and caspase-3 activation. This finding may further help understanding of the mechanism of glutamate-induced neuronal death and CAPE-induced neuroprotection against excitotoxicity.

Evaluation of the mechanical spectrum of the deposited materials in a composite system in torsion pendulum.

Previously, an approximate way to subtract the mechanical spectra (complex Young's modulus) of deposited materials from a composite reed vibration was proposed [X. N. Ying, Physica B 387, 376 (2007)]. In this article, the way of subtraction of mechanical spectra of deposited materials was extended to the complex shear modulus by a composite torsion pendulum method. Previous approximate formulas to calculate the mechanical spectra of deposited materials were found still to be valid except that new parameters were used. This deduction shows that previous approximate formulas are very applicable in the mechanical spectrum measurement. At last, the experimental result of glycerol was shown in approximate formulas.

Dendritic plasticity of CA1 pyramidal neurons after transient global ischemia.

Dendrites and spines undergo dynamic changes in physiological conditions, such as learning and memory, and in pathological conditions, such as Alzheimer's disease and epilepsy. Long-term dendritic plasticity has also been reported after ischemia/hypoxia, which might be compensatory effects of surviving neurons for the functional recovery after the insults. However, the dendritic changes shortly after ischemia, which might be associated with the pathogenesis of ischemic cell death, remain largely unknown. To reveal the morphological changes of ischemia-vulnerable neurons after ischemia, the present study investigated the alteration of dendritic arborization of CA1 pyramidal neurons in rats after transient cerebral ischemia using intracellular staining technique in vivo. The general appearance of dendritic arborization of CA1 neurons within 48 h after ischemia was similar to that of control neurons. However, a dramatic increase of dendritic disorientation was observed after ischemia with many basal dendrites coursed into the territory of apical dendrites and apical dendrites branched into the region of basal dendrites. In addition, a significant increase of apical dendritic length was found 24 h after ischemia. The increase of dendritic length after ischemia was mainly due to the dendritic sprouting rather than the extension of individual dendrites, which mainly occurred in the middle segment of the apical dendrites. These results reveal a plasticity change in dendritic arborization of CA1 neurons shortly after cerebral ischemia.

Genome-Wide Identification of the AP2/ERF Gene Family Involved in Active Constituent Biosynthesis in.

Tanshinones and phenolic acids are the major bioactive constituents in the traditional medicinal crop ; however, transcription factors (TFs) are seldom investigated with regard to their regulation of the biosynthesis of these compounds. Here a complete overview of the APETALA2/ethylene-responsive factor (AP2/ERF) transcription factor family in is provided, including phylogeny, gene structure, conserved motifs, and gene expression profiles of different organs (root, stem, leaf, flower) and root tissues (periderm, phloem, xylem). In total, 170 AP2/ERF genes were identified and divided into five relatively conserved subfamilies, including AP2 (25 genes), DREB (61 genes), ethylene responsive factor (ERF; 79 genes), RAV (4 genes), and Soloist (1 gene). According to the distribution of bioactive constituents and the expression patterns of AP2/ERF genes in different organs and root tissues, the genes related to the biosynthesis of bioactive constituents were selected. On the basis of quantitative real-time polymerase chain reaction (qRT-PCR) analysis, coexpression analysis, and the prediction of -regulatory elements in the promoters, we propose that two genes ( and ) regulate tanshinone biosynthesis and two genes ( and ) participate in controlling phenolic acid biosynthesis. The genes related to tanshinone biosynthesis belong to the ERF-B3 subgroup. In contrast, the genes predicted to regulate phenolic acid biosynthesis belong to the ERF-B1 and ERF-B4 subgroups. These results provide a foundation for future functional characterization of AP2/ERF genes to enhance the biosynthesis of the bioactive compounds of .

Prolonged membrane potential depolarization in cingulate pyramidal cells after digit amputation in adult rats.

The anterior cingulate cortex (ACC) plays an important role in higher brain functions including learning, memory, and persistent pain. Long-term potentiation of excitatory synaptic transmission has been observed in the ACC after digit amputation, which might contribute to plastic changes associated with the phantom pain. Here we report a long-lasting membrane potential depolarization in ACC neurons of adult rats after digit amputation in vivo. Shortly after digit amputation of the hind paw, the membrane potential of intracellularly recorded ACC neurons quickly depolarized from approximately -70 mV to approximately -15 mV and then slowly repolarized. The duration of this amputation-induced depolarization was about 40 min. Intracellular staining revealed that these neurons were pyramidal neurons in the ACC. The depolarization is activity-dependent, since peripheral application of lidocaine significantly reduced it. Furthermore, the depolarization was significantly reduced by a NMDA receptor antagonist MK-801. Our results provide direct in vivo electrophysiological evidence that ACC pyramidal cells undergo rapid and prolonged depolarization after digit amputation, and the amputation-induced depolarization in ACC neurons might be associated with the synaptic mechanisms for phantom pain.

Increase of delayed rectifier potassium currents in large aspiny neurons in the neostriatum following transient forebrain ischemia.

Large aspiny (LA) neurons in the neostriatum are resistant to cerebral ischemia whereas spiny neurons are highly vulnerable to the same insult. Excitotoxicity has been implicated as the major cause of neuronal damage after ischemia. Voltage-dependent potassium currents play important roles in controlling neuronal excitability and therefore influence the ischemic outcome. To reveal the ionic mechanisms underlying the ischemia-resistance, the delayed rectifier potassium currents (Ik) in LA neurons were studied before and at different intervals after transient forebrain ischemia using brain slices and acute dissociation preparations. The current density of Ik increased significantly 24 h after ischemia and returned to control levels 72 h following reperfusion. Among currents contributing to Ik, the margatoxin-sensitive currents increased 24 h after ischemia while the KCNQ/M current remained unchanged after ischemia. Activation of protein kinase A (PKA) down-regulated Ik in both control and ischemic LA neurons, whereas inhibition of PKA only up-regulated Ik and margatoxin-sensitive currents 72 h after ischemia, indicating an active PKA regulation on Ik at this time. Protein tyrosine kinases had a tonic inhibition on Ik to a similar extent before and after ischemia. Compared with that of control neurons, the spike width was significantly shortened 24 h after ischemia due to facilitated repolarization, which could be reversed by blocking margatoxin-sensitive currents. The increase of Ik in LA neurons might be one of the protective mechanisms against ischemic insult.

Restoration of thalamostriatal projections in rat neostriatal grafts: an electron microscopic analysis.

The thalamostriatal projections to rat neostriatal grafts were studied by using the Phaseolus vulgaris-leucoagglutinin (PHA-L) axonal tracing technique. Two to 6 months after implantation of striatal primordia into adult neostriata, PHA-L was injected into two different portions of the intralaminar nuclear complex of the thalamus. In the host neostriatum, labeled fibers from the parafascicular nucleus (PF) arborized in a large region in the neostriatum, but avoided small patchlike areas. Most of the fibers from PF had irregular curved trajectories with short side branches that formed boutons. Labeled fibers from the centromedial and paracentral nuclei (CeM-PC) projected to a similarly large area within the neostriatum but did not show any nonuniformity. CeM-PC axons had relatively straight trajectories and formed boutons en passant. Both sets of thalamostriatal projection fibers were found in the grafts. Some of the labeled fibers in the grafts formed dense, focal arborizations. Compared to the host neostriatum, the distribution of postsynaptic elements in the grafts was altered dramatically. In the host neostriatum, 89% of the terminals from PF terminated onto dendritic shafts; 93% of the CeM-PC terminals contacted dendritic spines. However, only 47% of the PF terminals in the grafts contacted dendritic shafts; 53% of them terminated on dendritic spines. In grafts, 81% of the terminals from CeM-PC region contacted dendritic spines; 19% of them made synapses on dendritic shafts. The shift of postsynaptic elements in the grafts suggests a loss of pathway specificity in the induction of dendritic spines on neostriatal neurons in grafts.

Neurophysiological changes of spiny neurons in rat neostriatum after transient forebrain ischemia: an in vivo intracellular recording and staining study.

The spontaneous activities, evoked postsynaptic potentials and membrane properties of spiny neurons in rat neostriatum were compared before, during and after 5-8 min ischemia using intracellular recording and staining techniques in vivo. Severe forebrain ischemia was induced with the four-vessel occlusion method. Approximately 2.5 min after the onset of ischemia the baseline membrane potential quickly depolarized to -20 mV and remained at this level during ischemia. Repolarization began within 2 min after recirculation. The onset of ischemic depolarization was directly related to the severity of ischemia and its latency was inversely related to brain temperature. Spontaneous firing and membrane potential fluctuation of spiny neurons ceased immediately after ischemia and slowly recovered several hours after recirculation. No neuronal hyperactivity was observed up to 7 h after recirculation. Cortically evoked inhibitory postsynaptic potentials and late depolarizations disappeared earlier after ischemia and recovered later following recirculation than the initial excitatory postsynaptic potentials. Membrane input resistance of spiny neurons was significantly increased but the time constant remained the same following recirculation. The rheobase and spike threshold of spiny neurons were significantly increased and the repetitive firing evoked by depolarizing current pulse was suppressed shortly after recirculation. The results of the present study indicated that the spontaneous activity and evoked postsynaptic responses of spiny neurons are suppressed and the excitability of spiny neurons is decreased after transient ischemia. The polysynaptic responses are more sensitive to ischemia than the monosynaptic ones.

In vivo intracellular demonstration of an ischemia-induced postsynaptic potential from CA1 pyramidal neurons in rat hippocampus.

Pyramidal neurons in the CA1 field of the hippocampus die a few days after transient cerebral ischemia. Excessive excitatory synaptic activation following reperfusion is thought to be responsible for such delayed cell death. However, it remains controversial whether excitatory synaptic transmission in the CA1 field is increased following reperfusion. Here we report a novel postsynaptic potential evoked from CA1 pyramidal neurons preceding cell death after transient forebrain ischemia with intracellular recording and staining techniques in vivo. This result indicates the dramatic alteration of synaptic transmission in CA1 neurons after transient ischemia. The ischemia-induced postsynaptic potential may be associated with the postischemic neuronal injury.

Alterations of single potassium channel activity in CA1 pyramidal neurons after transient forebrain ischemia.

Selective neuronal injury in the CA1 zone of hippocampus following transient cerebral ischemia has been well documented. Extracellular potassium concentration markedly increases during ischemia/hypoxia. Accumulating evidence has indicated that the outward potassium currents, including delayed rectifier potassium current, not only influence membrane excitability but also mediate apoptosis. It has been shown that the amplitude of delayed rectifier potassium current in CA1 neurons significantly increased after cerebral ischemia. To elucidate the mechanisms underlying the changes of potassium currents following ischemia, single potassium channel activities of rat CA1 neurons were compared before and after transient forebrain ischemia. Using cell-attached configuration, depolarizing voltage steps activated outward single channel events. The channel properties, the kinetics and pharmacology of these events resemble the delayed rectifier potassium current. After ischemia, the unitary amplitude of single channels significantly increased, the open probability, mean open time and open time constant also significantly increased while the conductance remained unchanged. These data indicate that the increase of single channel activity is responsible, at least in part, for the increase of delayed rectifier potassium current in CA1 neurons after cerebral ischemia.

Morphology of intracellularly stained spiny neurons in rat striatal grafts.

Two to six months after implantation of fetal striatal primordia into the kainic acid-lesioned neostriatum of adult rats, spiny neurons in the grafts were stained intracellularly with biocytin. To determine whether the spiny neurons in the grafts differentiate morphologically as in the host neostriatum, the intracellularly stained spiny neurons in the grafts were studied with light and electron microscopy and compared with that of spiny neurons in the host neostriatum. The spiny neurons in the grafts had ovoid or polygonal cell bodies with dendrites radiating in all directions. The somata were smooth and the dendrites, except for their most proximal portions, were rich in spines. All these features resembled the appearance of spiny neurons in the intact neostriatum. However, quantitative studies showed that the somata of spiny neurons in the grafts were larger than those in the host neostriatum (projected cross-sectional areas of 230 +/- 64.6 microns 2 in the grafts and 158 +/- 28.9 microns 2 in the host) and the spine density of graft neurons was lower than that of host neurons. Cells near the border of the grafts had dendrites extending both into the graft and into the host neostriatum. In these cells, the dendrites in the grafts had fewer spines than the dendrites in the host tissue. The axons of spiny neurons in the grafts had very large and dense intrastriatal collateral arborizations, which occupied a much larger volume than that of the dendritic domain of the parent cells. The local axonal arborizations of each of these cells filled almost the entire graft. In some cells, axonal branches were traced outside the grafts and were seen to enter the internal capsule fascicles. Unlike spiny neurons in the normal adult neostriatum, the spiny cells of the graft could have nuclear indentations. With this exception, the ultrastructural features of spiny neurons in the grafts were very similar to those in the hosts. Many unlabeled boutons made synapses on identified spiny neurons in the grafts. Terminals with small round vesicles made synaptic contacts on dendritic shafts and dendritic spines, while terminals with flattened or pleomorphic vesicles contacted somata, dendrites, and dendritic spines. Labeled axon collaterals of graft neurons made symmetrical synapses on somata, dendrites and spines in the grafts and in the host neostriatum. In the grafts, more than 60% of the axon terminals contacted dendritic shafts. The proportion of axosomatic and axospinous synapses varied substantially from cell to cell.(ABSTRACT TRUNCATED AT 250 WORDS)