5-aminolevulinic enhanced brain lesions mimic glioblastoma: A case report and literature review.

RATIONALE: Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor for which maximal tumor resection plays an important role in the treatment strategy. 5-aminolevulinic (5-ALA) is a powerful tool in fluorescence-guided surgery for GBM. However, 5-ALA- enhancing lesion can also be observed with different etiologies. PATIENTS CONCERNS: Three cases of 5-ALA-enhancing lesions with etiologies different from glioma. DIAGNOSES: The final diagnosis was abscess in 1 patient and diffuse large B-cell in the other 2 patients. INTERVENTIONS: Three patients received 5-aminolevulinic acid-guided tumor resection under microscope with intraoperative neuromonitoring. OUTCOMES: All of our patients showed improvement or stable neurological function outcomes. The final pathology revealed etiologies different from GBM. LESSONS: The 5-aminolevulinic acid fluorescence-guided surgery has demonstrated its maximal extent of resection and safety profile in patients with high-grade glioma. Non-glioma etiologies may also mimic GBM in 5-ALA-guided surgeries. Therefore, patient history taking and consideration of brain images are necessary for the interpretation of 5-ALA-enhanced lesions.

Unlocking Colchicine's Untapped Potential: A Paradigm Shift in Hepatocellular Carcinoma Prevention.

Background: Liver cancer and notably hepatocellular carcinoma (HCC), results in significantly high mortality rates worldwide. Chronic hepatitis and fatty liver, recognized precursors, underscore the imperative need for effective preventive strategies. This study explores colchicine, traditionally acknowledged for its anti-inflammatory properties and investigates its potential in liver cancer prevention. Methods: Utilizing the iHi Data Platform of China Medical University Hospital, Taiwan, this study analyzed two decades of medical data, incorporating 10,353 patients each in the Colchicine and Non-Colchicine cohorts, to investigate the association between colchicine use and liver cancer risk. Results: The study identified that colchicine users exhibited a 19% reduction in liver cancer risk, with a multivariable-adjusted odds ratio of 0.81 after accounting for confounding variables. Additionally, the influence of gender and comorbidities like diabetes mellitus on liver cancer risk was identified, corroborating the existing literature. A notable finding was that the prolonged use of colchicine was associated with improved outcomes, indicating a potential dose-response relationship. Conclusions: This study proposes a potential new role for colchicine in liver cancer prevention, extending beyond its established anti-inflammatory applications. While the findings are promising, further research is essential to validate these results. This research may serve as a foundation for future studies, aiming to further explore colchicine's role via clinical trials and in-depth investigations, potentially impacting preventive strategies for liver cancer.

Rosai-Dorfman disease mimicking craniopharyngioma: a challenging differential diagnosis. Illustrative case.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare non-Langerhans histiocytic disorder with less than 5% central nervous system involvement and is often mistaken for meningioma given the similarity in imaging features. The authors present the unique case of a 44-year-old female who presented with ongoing visual impairment. OBSERVATIONS: A purely suprasellar mass was noted on magnetic resonance imaging and was initially diagnosed as craniopharyngioma. Unexpectedly, the pathology report revealed RDD. LESSONS: To date, only six cases of sellar RDD have been reported, and our case is the first reported with a purely suprasellar presentation. No standard treatment has been established for RDD, and next-generation sequencing may be a promising therapeutic option.

Images Combined With Surgical Procedures and Pathological Identification to Distinguish a Reactive Histiocytosis With Organized Hematoma From a Malignant Peripheral Nerve Sheath Tumor.

BACKGROUND/AIM: Malignant peripheral nerve sheath tumors (MPNST) are rare soft tissue malignant tumors. To the best of our knowledge, there have been no previous reports of benign reactive histiocytosis with hematoma that mimics MPNST on medical images. CASE REPORT: A 57-year-old female with past history of hypertension came to our clinic due to low back pain with radiculopathy which was diagnosed with a tumor arising from L2 neuroforamen with L2 pedical erosion. Initial tentative diagnosis on the images was MPNST. However, after surgical resection, the pathologic report revealed no evidence of malignancy but only an organized hematoma with reactive histiocytosis. CONCLUSION: Images cannot provide enough diagnostic evidence for distinguishing a reactive histiocytosis from MPNST. Proper surgical procedures and expert pathological identification can correct the mistaking of the ambiguous identification as MPNST. Images can only provide precise and personalized medication accompanied by proper surgical procedures and expert pathological identification.

Case report of intracranial large vessel occlusion in glioblastoma multiforme patient after radiation therapy.

INTRODUCTION: Vasculopathy of the large arteries is a prominent complication of radiotherapy. Radiation-induced cerebral vasculopathy can cause arterial stenosis/occlusion, cerebral hemorrhage, and aneurysm formation. We report a cases of glioblastoma multiforme (GBM) with occlusive radiation vasculopathy (ORV). CASE PRESENTATION: This 28-year-old patient who suffered from GBM had surgery for cytoreduction and received postoperative CCRT. We adopted the radiotherapy and oncology group radiation guideline. This patient had cerebrovascular accident episodes without any known risk. Therefore, ORV was highly suspected and vascular stenosis was confirmed using magnetic resonance angiography (MRA) or digital subtraction angiography. Extracranial-intracranial bypass was performed and patency was confirmed. The patient had not suffered from recurrent symptoms of transient ischemic attack or ischemic stroke for 1.5 years. DISCUSSION: This is the first article to report bypass surgery for GBM patients. Although the median survival rate of GBM is approximately 15 months, the short survival time may be sufficient for occlusive vasculopathy to occur. Regular follow-up magnetic resonance imaging assessments are recommended, as is MRA as a screening tool for the early diagnosis of ORV.The Stenting versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial focused on atherosclerotic intracranial arterial stenosis, revealing that aggressive medical management was superior to stenting for secondary stroke prevention; however, it did not mention radiation-induced vasculopathy. Bypass surgery has yielded some positive outcomes. In the absence of contraindications, antiplatelet or anticoagulation agents could be added, and bypass surgery could be performed because there was no stent in the distal intracranial arteries. CONCLUSION: MRA is a potential screening tool for ORV in GBM patients and bypass surgery could be performed to improve brain perfusion. Bypass surgery could help patient with occlusive radiation vasculopathy.

Universal scaling of extinction time in stochastic evolutionary dynamics.

Evolutionary dynamics is well captured by the replicator equations when the population is infinite and well-mixed. However, the extinction dynamics is modified with finite and structured populations. Experiments on the non-transitive ecosystem containing three populations of bacteria found that the ecological stability sensitively depends on the spatial structure of the populations. Based on the Reference-Gamble-Birth algorithm, we use agent-based Monte Carlo simulations to investigate the extinction dynamics in the rock-paper-scissors ecosystem with finite and structured populations. On the fully-connected network, the extinction time in stable and unstable regimes falls into two universal functions when plotted with the rescaled variables. On the two dimensional grid, the spatial structure changes the transition boundary between stable and unstable regimes but doesn't change its extinction trend. The finding of universal scaling in extinction dynamics is unexpected, and may provide a powerful method to classify different evolutionary dynamics into universal classes.

Patient-derived tumor organoids as a platform of precision treatment for malignant brain tumors.

Malignant brain tumors consist of malignancies originated primarily within the brain and the metastatic lesions disseminated from other organs. In spite of intensive studies, malignant brain tumors remain to be a medical challenge. Patient-derived organoid (PDO) can recapitulate the biological features of the primary tumor it was derived from and has emerged as a promising drug-screening model for precision therapy. Here we show a proof-of-concept based on early clinical study entailing the organoids derived from the surgically resected tumors of 26 patients with advanced malignant brain tumors enrolled during December 2020 to October 2021. The tumors included nine glioma patients, one malignant meningioma, one primary lymphoma patient, and 15 brain metastases. The primary tumor sites of the metastases included five from the lungs, three from the breasts, two from the ovaries, two from the colon, one from the testis, one of melanoma origin, and one of chondrosarcoma. Out of the 26 tissues, 13 (50%) organoids were successfully generated with a culture time of about 2 weeks. Among these patients, three were further pursued to have the organoids derived from their tumor tissues tested for the sensitivity to different therapeutic drugs in parallel to their clinical care. Our results showed that the therapeutic effects observed by the organoid models were consistent to the responses of these patients to their treatments. Our study suggests that PDO can recapitulate patient responses in the clinic with high potential of implementation in personalized medicine of malignant brain tumors.

Elevation of hilar mossy cell activity suppresses hippocampal excitability and avoidance behavior.

Modulation of hippocampal dentate gyrus (DG) excitability regulates anxiety. In the DG, glutamatergic mossy cells (MCs) receive the excitatory drive from principal granule cells (GCs) and mediate the feedback excitation and inhibition of GCs. However, the circuit mechanism by which MCs regulate anxiety-related information routing through hippocampal circuits remains unclear. Moreover, the correlation between MC activity and anxiety states is unclear. In this study, we first demonstrate, by means of calcium fiber photometry, that MC activity in the ventral hippocampus (vHPC) of mice increases while they explore anxiogenic environments. Next, juxtacellular recordings reveal that optogenetic activation of MCs preferentially recruits GABAergic neurons, thereby suppressing GCs and ventral CA1 neurons. Finally, chemogenetic excitation of MCs in the vHPC reduces avoidance behaviors in both healthy and anxious mice. These results not only indicate an anxiolytic role of MCs but also suggest that MCs may be a potential therapeutic target for anxiety disorders.

Recombinant Baculovirus: A Flexible Drug Screening Platform for Chikungunya Virus.

Chikungunya virus (CHIKV) is a mosquito-transmitted infectious agent that causes an endemic or epidemic outbreak(s) of Chikungunya fever that is reported in almost all countries. This virus is an intense global threat, due to its high rate of contagion and the lack of effective remedies. In this study, we developed two baculovirus expression vector system (BEVS)-based approaches for the screening of anti-CHIKV drugs in Spodoptera frugiperda insect (Sf21) cells and U-2OS cells. First, structural protein of CHIKV was co-expressed through BEVS and thereby induced cell fusion in Sf21 cells. We used an internal ribosome entry site (IRES) to co-express the green fluorescent protein (EGFP) for identifying these fusion events. The EGFP-positive Sf21 cells fused with each other and with uninfected cells to form syncytia. We identified that ursolic acid has potential anti-CHIKV activity in vitro, by using this approach. Second, BacMam virus-based gene delivery has been successfully applied for the transient expression of non-structural proteins with a subgenomic promoter-EGFP (SP-EGFP) cassette in U-2OS cells to act as an in vitro CHIKV replicon system. Our BacMam-based screening system has identified that the potential effects of baicalin and baicalein phytocompounds can inhibit the replicon activity of CHIKV in U-2OS cells. In conclusion, our results suggested that BEVS can be a potential tool for screening drugs against CHIKV.

Use of a Smartphone Application to Speed Up Interhospital Transfer of Acute Ischemic Stroke Patients for Thrombectomy.

Background: In most countries, large cerebral artery occlusion is identified as the leading cause of disability. In 2015, five large-scale clinical trials confirmed the benefit of intra-arterial thrombectomy. However, thrombectomy is a highly technical and facility-dependent procedure. Primary stroke centers need to transfer patients to comprehensive stroke centers to perform thrombectomy. The time-lapse during interhospital transfer would decrease the chance of the patient's proper recovery. Communication barriers also contribute to this delay. Aims: We used a smartphone application to overcome communication barriers between hospitals. We aimed to shorten the door-to-puncture time of interhospital transfer patients. Methods: We began using a smartphone application, "LINE," to facilitate interhospital communication on May 01, 2018. We carried out retrospective data analyses for all the transfer patients (n = 351), with the primary outcome being the door-to-puncture time in our comprehensive stroke center (China Medical University Hospital). We compared the three periods: May 01 to Dec 31, 2017 (before the use of the smartphone application); May 01 to Dec 31, 2018 (the 1st year of using the smartphone application); and May 01 to Dec 31, 2019 (the 2nd year of using the smartphone application). We also compared the transfer data with non-transfer thrombectomies in the same period. Results: We compared 2017, 2018, and 2019 data. The total number of transfer patients increased over the years: 63, 113, 175, respectively. The mean door-to-puncture time decreased significantly, going from 109, through 102, to 92 min. Meanwhile, the mean door-to-puncture time in non-transfer patients were 140.3, 122.1, and 129.3 min. The main reason of time saving was the change of the way of communication, from point-to-point interhospital communication to hub-to-spoke interhospital communication. Conclusions: We used this smartphone application to enhance interhospital communication, changed from the point-to-point to hub-to-spoke method. It made us overcome the communication barrier and build up interhospital connection, thus shortening the door-to-puncture time. Our experience demonstrated the importance of close communication and teamwork in hyperacute stroke care, especially in interhospital transfer for thrombectomy.

Anticipation and negative group delay in a retina.

The mechanism of negative group delay (NGD) is used to understand the anticipatory capability of a retina. Experiments with retinas from bullfrogs are performed to compare with the predictions of the NGD model. In particular, whole field stochastic stimulations with various autocorrelation times are used to probe anticipatory responses from the retina. We find that the NGD model can reproduce essential features of experimental observations characterized by the cross correlations between the stimulation and the retinal responses. Experiments with dark light pulse stimulations further support the NGD mechanism, with the retina producing time-advanced pulse responses. However, no time-advanced pulse responses are produced by bright pulses. Counterintuitively, the NGD model shows that it is the delay in the system which gives rise to anticipation because of the negative feedback adaptation mechanism.

Analysis of Environmental and Typhoon Effects on Modal Frequencies of a Power Transmission Tower.

The structural health monitoring of power transmission towers (PTTs) has drawn increasing attention from researchers in recent years; however, no long-term monitoring of the dynamic parameters of PTTs has previously been reported in the literature. This study performed the long-term monitoring of an instrumented PTT. An automated subspace identification technique was used to extract the dynamic parameters of the PTT from ambient vibration measurements taken over approximately ten months in 2017. Ten target modal frequencies were selected to explore the effects of environmental factors, such as temperature and wind speed, as well as the root-mean-square (RMS) acceleration response of the PTT. Variations in the modal frequencies of approximately 2% to 8% were observed during the study period. In general, among the environmental factors, the temperature was found to be the primary cause of decreases in the modal frequencies, except in the case of some of the higher modes. Typhoon Nesat, which affected the PTT on July 29th, 2017, seems to have decreased the modal frequencies of the PTT, especially for the higher modes. This reduction in the modal frequencies seems to have lasted for approximately two and a half months, after which they recovered to their normal state, probably due to a seasonal cool down in temperature. The reduction percentages in the modal frequencies due to Typhoon Nesat were quantified as approximately -0.89% to -1.34% for the higher modes, but only -0.07% to -0.46% for the remaining lower modes. Although the unusual reductions in the modal frequencies are reported in this study, the reason for this phenomenon is not clear yet. Further studies would be required in the future in order to find the cause.

Astrocytic Regulation of Synchronous Bursting in Cortical Cultures: From Local to Global.

Synchronous bursting (SB) is ubiquitous in neuronal networks and independent of network structure. Although it is known to be driven by glutamatergic neurotransmissions, its underlying mechanism remains unclear. Recent studies show that local glutamate recycle by astrocytes affects nearby neuronal activities, which indicate that the local dynamics might also be the origin of SBs in networks. We investigated the effects of local glutamate dynamics on SBs in both cultures developed on multielectrode array (MEA) systems and a tripartite synapse simulation. Local glutamate uptake by astrocytes was altered by pharmacological targeting of GLT-1 glutamate transporters, whereas neuronal firing activities and synaptic glutamate level was simultaneously monitored with MEA and astrocyte-specific glutamate sensors (intensity-based glutamate-sensing fluorescent reporter), respectively. Global SB properties were significantly altered on targeting GLT-1. Detailed simulation of a network with astrocytic glutamate uptake and recycle mechanisms, conforming with the experimental observations, shows that astrocytes function as a slow negative feedback to neuronal activities in the network. SB in the network can be realized as an alternation between positive and negative feedback in the neurons and astrocytes, respectively. An understanding of glutamate trafficking dynamics is of general application to explain how astrocyte malfunction can result in pathological seizure-like phenomena in neuronal systems.

Long-Term Follow-up in Patients with Spontaneous Intracerebral Hemorrhage Treated With or Without Surgical Intervention: a Large-Scale Retrospective Study.

Debates regarding the most beneficial medical or surgical procedures for patients with spontaneous intracerebral hemorrhage (sICH) are still ongoing. We aimed to evaluate the risk of subsequent vascular disease and mortality in patients with sICH treated with and without surgical intervention, in a large-scale Asian population. Patients hospitalized within 2000 to 2013 who were newly diagnosed with sICH were identified using the National Health Insurance Research Database of Taiwan. Neuroendoscopy and craniotomy groups comprised patients who underwent surgical treatment within 1 week, while those in the control group did not undergo early surgical treatment. Outcomes included subsequent hemorrhagic and ischemic stroke, following acute myocardial infarction, congestive heart failure, and mortality. After propensity score matching, there were 663 patients in each group. Compared to that in the control group, the neuroendoscopy and craniotomy groups had a significantly higher risk of secondary vascular events at 1 to 3 months of follow-up (adjusted HR, 2.08 and 1.95; 95% CI, 1.21-3.58 and 1.13-3.35; p < 0.01 and p < 0.05, respectively), but a significantly lower risk after 3 years of follow-up (adjusted HR, 0.52 and 0.52; 95% CI, 0.35-0.78 and 0.35-0.77; p < 0.01 and p < 0.01, respectively). The mortality rate was higher in the craniotomy group at 6 to 12 months of follow-up (adjusted HR, 2.18; 95% CI, 1.06-4.49; p < 0.05) compared to that in the control group. Thus, a timely surgical intervention for hematoma evacuation is advantageous in preventing secondary vascular events and improving outcomes in the long term. However, greater attention to secondary ischemic stroke following the initial sICH episode is needed.

Patient Transfer Decision Difficulty Scale: Development and psychometric testing of emergency department visits by long-term care residents.

BACKGROUND AND OBJECTIVES: Nurses serve as gatekeepers of the health of long-term care facility (LTCF) residents and are key members deciding whether residents should visit an emergency department (ED). Inappropriate decisions as to ED visits may result in ED overcrowding, excessive medical expenses, and nosocomial infections. Currently, there is a lack of effective tools for assessing the barriers and level of difficulty experienced by LTCF nurses. The purposes of this study were to develop a Patient Transfer Decision Difficulty Scale (PTDDS) and test its effectiveness. METHODS: This study randomly sampled LTCFs in Taiwan and surveyed two or three nurses in every institution selected. Registered return envelopes were provided for participants to return self-completed questionnaires. Three steps were used to develop the scale and items: in step I, the instrument was developed; in step II, psychometric testing was conducted, which entailed performing an exploratory factor analysis (EFA) to verify the construct validity and reliability of the developed items; and in step III, a confirmation study was conducted using a confirmatory factor analysis (CFA) and structural equation modeling to cross-validate the factors and items. RESULTS: The cumulative sum of variance explained by the measurement models of the three factors in the PTDDS was 63.54%.When deciding whether to transfer LTCF residents to EDs, the most pronounced barrier experienced by nurses were for judging the severity of "clinical episodes", which had an explanatory power of 37.49%. The second and third pronounced barriers and decision difficulty experienced by nurses were "communication and information" and "timing of the residents' emergency visits," which explained 16.81% and 9.24% of the variance, respectively. CONCLUSIONS: The cross-validation results obtained using the EFA and CFA showed favorable reliability and validity of the PTDDS. For future studies, this study recommends performing large-scale investigations of the level of decision difficulty and related factors experienced by nurses in LTCFs of varying levels and types.

Risk of subsequent stroke, with or without extracranial-intracranial bypass surgery: a nationwide, retrospective, population-based study.

OBJECTIVEAlthough no benefits of extracranial-intracranial (EC-IC) bypass surgery in preventing secondary stroke have been identified previously, the outcomes of initial symptomatic ischemic stroke and stenosis and/or occlusion among the Asian population in patients with or without bypass intervention have yet to be discussed. The authors aimed to evaluate the subsequent risk of secondary vascular disease and cardiac events in patients with and without a history of this intervention.METHODSThis retrospective nationwide population-based Taiwanese registry study included 205,991 patients with initial symptomatic ischemic stroke and stenosis and/or occlusion, with imaging data obtained between 2001 and 2010. Patients who underwent EC-IC bypass (bypass group) were compared with those who had not undergone EC-IC bypass, carotid artery stenting, or carotid artery endarterectomy (nonbypass group). Patients with any previous diagnosis of ischemic or hemorrhagic stroke, moyamoya disease, cancer, or trauma were all excluded.RESULTSThe risk of subsequent ischemic stroke events decreased by 41% in the bypass group (adjusted hazard ratio [HR] 0.59, 95% CI 0.46-0.76, p < 0.001) compared with the nonbypass group. The risk of subsequent hemorrhagic stroke events increased in the bypass group (adjusted HR 2.47, 95% CI 1.67-3.64, p < 0.001) compared with the nonbypass group.CONCLUSIONSBypass surgery does play an important role in revascularization of the ischemic brain, while also increasing the risk of hemorrhage in the early postoperative period. This study highlights the fact that the high risk of bypass surgery obscures the true benefit of revascularization of the ischemic brain and also emphasizes the importance of developing improved surgical technique to treat these high-risk patients.

Local hemostatic matrix for endoscope-assisted removal of intracerebral hemorrhage is safe and effective.

BACKGROUND/PURPOSE: Minimally invasive endoscope-assisted (MIE) evacuation of spontaneous intracerebral hemorrhage (ICH) is simple and effective, but the limited working space may hinder meticulous hemostasis and might lead to rebleeding. Management of intraoperative hemorrhage is therefore a critical issue of this study. This study presents experience in the treatment of patients with various types of ICH by MIE evacuation followed by direct local injection of FloSeal Hemostatic Matrix (Baxter Healthcare Corp, Fremont, CA, USA) for hemostasis. METHODS: The retrospective nonrandomized clinical and radiology-based analysis enrolled 42 patients treated with MIE evacuation of ICH followed by direct local injection of FloSeal Hemostatic Matrix. Rebleeding, morbidity, and mortality were the primary endpoints. The percentage of hematoma evacuated was calculated from the pre- and postoperative brain computed tomography (CT) scans. Extended Glasgow Outcome Scale (GOSE) was evaluated at 6 months postoperatively. RESULTS: Forty-two ICH patients were included in this study, among these, 23 patients were putaminal hemorrhage, 16 were thalamic ICH, and the other three were subcortical type. Surgery-related mortality was 2.4%. The average percentage of hematoma evacuated was 80.8%, and the rebleeding rate was 4.8%. The mean operative time was 102.7 minutes and the average blood loss was 84.9 mL. The mean postoperative GOSE score was 4.55 at 6-months' follow-up. CONCLUSION: This study shows that local application of FloSeal Hemostatic Matrix is safe and effective for hemostasis during MIE evacuation of ICH. In our experience, this shortens the operation time, especially in cases with intraoperative bleeding. A large, prospective, randomized trial is needed to confirm the findings.

Inhibition of astrocytic activity alleviates sequela in acute stages of intracerebral hemorrhage.

Neurological deterioration of intracerebral hemorrhage (ICH) mostly occurs within the first 24 hours. Together with the microglia/macrophages (MMΦ), astrocytes are important cell population responsible for many brain injuries but rarely being highlighted in acute stage of ICH. In present study, we induced rats ICH either by collagenase or autologous blood injection. Experimental groups were classified as vehicle or Ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3) treatment group (n = 9, each group). MRI assessments after ICH were used to evaluate the hematoma progression and blood-brain barrier (BBB) integrity. The glia cells accumulations were examined by GFAP and Iba1 immunohistochemistry, respectively. Abundant astrocytes but few MMΦ were observed in hyperacute and acute ICH. Upon suppression of astrocyte activity, ICH rats exhibited decreased size of hematoma expansion, less BBB destruction, reduced astrocyte accumulation in perihematomal regions, postponed course of hemoresolution and gain better outcomes. These finding provide evidence that activated astrocytes are crucial cell populations in hyperacute and acute ICH, and their modulation may offer opportunities for novel therapy and patient management.

Positive feedback and synchronized bursts in neuronal cultures.

Synchronized bursts (SBs) with complex structures are common in neuronal cultures. Although the phenomenon of SBs has been discovered for a long time, its origin is still unclear. Here, we investigate the properties of these SBs in cultures grown on a multi-electrode array. We find that structures of these SBs are related to the different developmental stages of the cultures and these structures can be modified by changing the magnesium concentration in the culture medium; indicating that synaptic mechanism is involved in the generation of SBs. A model based on short term synaptic plasticity (STSP), recurrent connections and astrocytic recycling of neurotransmitters has been developed successfully to understand the observed structures of SBs in experiments. A phase diagram obtained from this model shows that networks exhibiting SBs are in a complex oscillatory state due to large enough positive feedback provided by synaptic facilitation and recurrent connections. In this model, while STSP controls the fast oscillations (∼ 100 ms) within a SB, the astrocytic recycling determines the slow time scale (∼10 s) of inter-burst intervals. Our study suggests that glia-neuron interactions can be important in the understanding of the complex dynamics of neuronal networks.