Technical details for a robot-assisted hand-sewn esophago-gastric anastomosis during minimally invasive Ivor Lewis esophagectomy.

BACKGROUND: Minimally invasive Ivor Lewis esophagectomy (MIILE) provides better outcomes than open techniques, particularly in terms of post-operative recovery and pulmonary complications. However, in addition to requiring advanced technical skills, thoracoscopic access makes it hard to perform esophagogastric anastomosis safely, and the reported rates of anastomotic leak vary from 5 to 16%. Several minimally invasive esophago-gastric anastomotic techniques have been described, but to date strong evidence to support one technique over the others is still lacking. We herein report the technical details and preliminary results of a new robot-assisted hand-sewn esophago-gastric anastomosis technique. METHODS: From January 2018 to December 2020, 12 cases of laparoscopic/thoracoscopic Ivor Lewis esophagectomy with robot-assisted hand-sewn esophago-gastric anastomosis were performed. The gastric conduit was prepared and tailored taking care of vascularization with a complete resection of the gastric fundus. The anastomosis consisted of a robot-assisted, hand-sewn four layers of absorbable monofilament running barbed suture (V-lock). The posterior outer layer incorporated the gastric and esophageal staple lines. RESULTS: The post-operative course was uneventful in nine cases. Two patients developed chyloperitoneum, one patient a Sars-Cov-2 infection, and one patient a late anastomotic stricture. In all cases, there were no anastomotic leaks or delayed gastric conduit emptying. The median post-operative stay was 13 days (min 7, max 37 days); the longest in-hospital stay was recorded in patients who developed chyloperitoneum. CONCLUSION: Despite the small series, we believe that our technique looks to be promising, safe, and reproducible. Some key points may be useful to guarantee a low complications rate after MIILE, particularly regarding anastomotic leaks and delayed emptying: the resection of the gastric fundus, the use of robot assistance, the incorporation of the staple lines in the posterior aspect of the anastomosis, and the use of barbed suture. Further cases are needed to validate the preliminary, but very encouraging, results.

NG2-glia and their functions in the central nervous system.

In the central nervous system, NG2-glia represent a neural cell population that is distinct from neurons, astrocytes, and oligodendrocytes. While in the past the main role ascribed to these cells was that of progenitors for oligodendrocytes, in the last years it has become more obvious that they have further functions in the brain. Here, we will discuss some of the most current and highly debated issues regarding NG2-glia: Do these cells represent a heterogeneous population? Can they give rise to different progenies, and does this change under pathological conditions? How do they respond to injury or pathology? What is the role of neurotransmitter signaling between neurons and NG2-glia? We will first give an overview on the developmental origin of NG2-glia, and then discuss whether their distinct properties in different brain regions are the result of environmental influences, or due to intrinsic differences. We will then review and discuss their in vitro differentiation potential and in vivo lineage under physiological and pathological conditions, together with their electrophysiological properties in distinct brain regions and at different developmental stages. Finally, we will focus on their potential to be used as therapeutic targets in demyelinating and neurodegenerative diseases. Therefore, this review article will highlight the importance of NG2-glia not only in the healthy, but also in the diseased brain.

SOX17 is expressed in regenerating oligodendrocytes in experimental models of demyelination and in multiple sclerosis.

We have previously demonstrated that Sox17 expression is prominent at developmental stages corresponding to oligodendrocyte progenitor cell (OPC) cycle exit and onset of differentiation, and that Sox17 promotes initiation of OPC differentiation. In this study, we examined Sox17 expression and regulation under pathological conditions, particularly in two animal models of demyelination/remyelination and in post-mortem multiple sclerosis (MS) brain lesions. We found that the number of Sox17 expressing cells was significantly increased in lysolecithin (LPC)-induced lesions of the mouse spinal cord between 7 and 30 days post-injection, as compared with controls. Sox17 immunoreactivity was predominantly detected in Olig2(+) and CC1(+) oligodendrocytes and rarely in NG2(+) OPCs. The highest density of Sox17(+) oligodendrocytes was observed at 2 weeks after LPC injection, coinciding with OPC differentiation. Consistent with these findings, in cuprizone-treated mice, Sox17 expression was highest in newly generated and in maturing CC1(+) oligodendrocytes, but low in NG2(+) OPCs during the demyelination and remyelination phases. In MS tissue, Sox17 was primarily detected in actively demyelinating lesions and periplaque white matter. Sox17 immunoreactivity was co-localized with NOGO-A+ post-mitotic oligodendrocytes both in active MS lesions and periplaque white matter. Taken together, our data: (i) demonstrate that Sox17 expression is highest in newly generated oligodendrocytes under pathological conditions and could be used as a marker of oligodendrocyte regeneration, and (ii) are suggestive of Sox17 playing a critical role in oligodendrocyte differentiation and lesion repair.

Betamethasone therapy in ataxia telangiectasia: unraveling the rationale of this serendipitous observation on the basis of the pathogenesis.

Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized by progressive neurological dysfunction. To date, only supportive care aimed to halt the progressive neurodegeneration is available for the treatment. Recently, an improvement of neurological signs during short-term treatment with betamethasone has been reported. To date, the molecular and biochemical mechanisms by which the steroid produces such effects have not yet been elucidated. Therefore, a review of the literature was carried out to define the potential molecular and functional targets of the steroid effects in A-T. Glucocorticoids (GCs) are capable of diffusing into the CNS by crossing the blood-brain barrier (BBB) where they exert effects on the suppression of inflammation or as antioxidant. GCs have been shown to protect post-mitotic neurons from apoptosis. Eventually, GCs may also modulate synaptic plasticity. A better understanding of the mechanisms of action of GCs in the brain is needed, because in A-T during the initial phase of cell loss the neurological impairment may be rescued by interfering in the biochemical pathways. This would open a new window of intervention in this so far incurable disease.

Use of spatiotemporal image correlation at 11-14 weeks' gestation.

OBJECTIVE: To assess prospectively the use of four-dimensional (4D) spatiotemporal image correlation (STIC) in the evaluation of the fetal heart at 11-14 weeks' gestation. METHODS: The study involved offline analysis of 4D-STIC volumes of the fetal heart acquired at 11-14 weeks' gestation in a population at high risk for congenital heart disease (CHD). Regression analysis was used to investigate the effect of gestational age, maternal body mass index, quality of the 4D-STIC volume, use of a transvaginal vs transabdominal probe and use of color Doppler ultrasonography on the ability to visualize separately different heart structures. The accuracy in diagnosing CHD based on early fetal echocardiography (EFE) using 4D-STIC vs conventional two-dimensional (2D) ultrasound was also evaluated. RESULTS: One hundred and thirty-nine fetuses with a total of 243 STIC volumes were included in this study. Regression analysis showed that the ability to visualize different heart structures was correlated with the quality of the acquired 4D-STIC volumes. Independently, the use of a transvaginal approach improved visualization of the four-chamber view, and the use of Doppler improved visualization of the outflow tracts, aortic arch and interventricular septum. Follow-up was available in 121 of the 139 fetuses, of which 27 had a confirmed CHD. A diagnosis based on EFE using 4D-STIC was possible in 130 (93.5%) of the 139 fetuses. Accuracy in diagnosing CHD using 4D-STIC was 88.7%, and the results of 45% of the cases were fully concordant with those of 2D ultrasound or the final follow-up diagnosis. EFE using 2D ultrasound was possible in all fetuses, and accuracy in diagnosing CHD was 94.2%. Five of the seven false-positive or false-negative cases were minor CHD. CONCLUSIONS: In fetuses at 11-14 weeks' gestation, the heart can be evaluated offline using 4D-STIC in a large number of cases, and this evaluation is more successful the higher the quality of the acquired volume. 2D ultrasound remains superior to 4D-STIC at 11-14 weeks, unless volumes of good to high quality can be obtained.

Virtual autopsy by computed tomographic angiography of the fetal heart: a feasibility study.

OBJECTIVE: To determine the feasibility of postmortem computed tomographic (pm-CT) angiography for fetal heart evaluation. METHODS: Following termination of pregnancy (TOP) or intrauterine fetal death (IUFD) beyond 18 weeks' gestation, 33 fetuses were examined by pm-CT; in eight contrast medium was injected through the umbilical cord and in 25 contrast medium was injected directly into the heart. Logistic regression analysis was used to investigate the effect on the ability to visualize cardiac structures on pm-CT angiography of gestational age at TOP or delivery following IUFD, the time delay between fetal death and examination, the technique used for contrast-medium injection, the presence of cardiac abnormalities and whether or not there was IUFD. The diagnostic accuracy of pm-CT angiography for the evaluation of fetal cardiac structures was also evaluated. RESULTS: Cardiac anatomy including heart situs, the four-chamber view and great vessels could be visualized on pm-CT angiography in 29 out of 33 fetuses (87.9%). Logistic regression analysis showed that the ability to visualize cardiac structures on pm-CT angiography was positively correlated only with contrast medium injected directly into the heart. Twenty-five out of the 33 fetuses underwent conventional autopsy. There were five cases with suspected major cardiac abnormality at prenatal ultrasound and one with a minor cardiac abnormality. In one of these cases, severe leakage into the pleural cavity did not allow for visualization of any heart structure on pm-CT angiography and in another invasive autopsy was declined. In two of the remaining four cases, the findings on pm-CT angiography and invasive autopsy were in agreement, while in two a ventricular septal defect was found on invasive autopsy but not on pm-CT. None of the 27 cases with normal hearts was falsely classified as abnormal using pm-CT angiography. CONCLUSION: Pm-CT angiography by direct injection into the heart seems to be a feasible method for its evaluation. The extent to which such a technique could be used for the evaluation of congenital heart disease as an alternative to classical postmortem autopsy remains to be determined.

Primary brain tumours and specific serum immunoglobulin E: a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Case-control studies suggest that patients with allergic diseases have a lower risk of developing glioma but not meningioma or schwannoma. However, those data can be differentially biased. Prospective studies with objective measurements of immunologic biomarkers, like immunoglobulin E (IgE), in blood obtained before cancer diagnosis could help to clarify whether an aetiological association exists. METHODS: The present case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) measured specific serum IgE as a biomarker for the most common inhalant allergens in 275 glioma, 175 meningioma and 49 schwannoma cases and 963 matched controls using the ImmunoCAP specific IgE test. Subjects with an IgE level ≥0.35 kUA/l (kilo antibody units per litre) were classified as sensitized by allergens. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by adjusted conditional logistic regression models for each tumour subtype. The effect of dose-response relationship was assessed in five increasing IgE level categories to estimate P-values for trend. RESULTS: The risk of glioma was inversely related to allergic sensitization (OR = 0.73; 95% CI 0.51-1.06), especially pronounced in women (OR = 0.53; 95% CI 0.30-0.95). In dose-response analyses, for high-grade glioma, the lowest OR was observed in sera with the highest IgE levels (P for trend = 0.04). No association was seen for meningioma and schwannoma. CONCLUSION: The results, based on serum samples prospectively collected in a cohort study, provide some support for the hypothesis that individuals with allergic sensitization are at reduced risk of glioma and confirm results from previous case-control studies.

Dietary beta-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

So far, studies on dietary antioxidant intake, including beta-carotene, vitamin C and vitamin E, and breast cancer risk are inconclusive. Thus, we addressed this question in the European Prospective Investigation into Cancer and Nutrition. During a median follow-up time of 8.8 years, 7,502 primary invasive breast cancer cases were identified. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). All analyses were run stratified by menopausal status at recruitment and, additionally, by smoking status, alcohol intake, use of exogenous hormones and use of dietary supplements. In the multivariate analyses, dietary intake of beta-carotene, vitamin C and E was not associated with breast cancer risk in premenopausal [highest vs. lowest quintile: HR, 1.04 (95% CI, 0.85-1.27), 1.12 (0.92-1.36) and 1.11 (0.84-1.46), respectively] and postmenopausal women [0.93 (0.82-1.04), 0.98 (0.87-1.11) and 0.92 (0.77-1.11), respectively]. However, in postmenopausal women using exogenous hormones, high intake of beta-carotene [highest vs. lowest quintile; HR 0.79 (95% CI, 0.66-0.96), P (trend) 0.06] and vitamin C [0.88 (0.72-1.07), P (trend) 0.05] was associated with reduced breast cancer risk. In addition, dietary beta-carotene was associated with a decreased risk in postmenopausal women with high alcohol intake. Overall, dietary intake of beta-carotene, vitamin C and E was not related to breast cancer risk in neither pre- nor postmenopausal women. However, in subgroups of postmenopausal women, a weak protective effect between beta-carotene and vitamin E from food and breast cancer risk cannot be excluded.

Panbiogeographical analysis of the shark genus Rhizoprionodon (Chondrichthyes, Carcharhiniformes, Carcharhinidae).

The distributional patterns of the seven species of Rhizoprionodon were analysed using the panbiogeographical method of track analysis. The individual tracks of Rhizoprionodon suggest that the genus is mainly an Indian-Atlantic Ocean group. Five generalized tracks were found: (1) Caribbean, defined by R. porosus and R. terraenovae; (2) eastern coast of South America, defined by R. porosus and R. lalandei; (3) Indian Ocean, defined by R. acutus and R. oligolinx; (4) north-western Australia, defined by R. acutus, R. oligolinx and R. taylori; (5) north-north-eastern Australia, defined by R. acutus and R. taylori. Only R. longurio was not included in any generalized track, and its distribution is restricted to the eastern Pacific Ocean. Two biogeographical nodes were found at the intersection of the generalized tracks 1 and 2 (Caribbean Sea) and generalized tracks 4 and 5 (north Australia). The generalized tracks overlap with those found in several unrelated marine taxa. Overall, the generalized tracks are associated with warm currents. The biogeographical nodes found (Caribbean and Australian) are coincident with the global distribution of mangroves.

One-year MRI scan predicts clinical response to interferon beta in multiple sclerosis.

BACKGROUND AND PURPOSE: To define the predictive value of clinical and magnetic resonance imaging (MRI) characteristics in identifying relapsing-remitting multiple sclerosis (RR-MS) patients with sustained disability progression during interferon beta (IFNB) treatment. METHODS: All patients receiving treatment with one of the available IFNB formulations for at least 1 year were included in this single-centre, prospective and post-marketing study. Demographic, clinical and MRI data were collected at IFNB start and at 1 year of therapy; patients were followed-up at least yearly. Poor clinical response was defined as the occurrence of a sustained disability progression of > or =1 point in the Expanded Disability Status Scale (EDSS) during the follow-up period. RESULTS: Out of 454 RR-MS patients starting IFNB therapy, data coming from 394 patients with a mean follow-up of 4.8 (2.4) years were analysed. Sixty patients were excluded because of too short follow-up. Less than 1/3 (30.4%) of the patients satisfied the criterion of 'poor responders'. Patients presenting new lesions on T2-weighted MRI scan after 1 year of therapy (compared with baseline) had a higher risk of being poor responder to treatment with IFNB during the follow-up period (HR 16.8, 95% CI 7.6-37.1, P < 0.001). An augmented risk increasing the number of lesions was observed, with a 10-fold increase for each new lesion. CONCLUSIONS: Developing new T2-hyperintense lesions during IFNB treatment was the best predictor of long-term poor response to therapy. MRI scans performed after 1 year of IFNB treatment may be useful in contributing to early identification of poor responders.

Measurement of the cosmic ray proton spectrum from 40 GeV to 100 TeV with the DAMPE satellite.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.

Neuronal fodrin proteolysis occurs independently of excitatory amino acid-induced neurotoxicity.

In cultured cerebellar granule cells, the total amount of fodrin alpha subunit increased 3-fold between 0 and 10 days in vitro and fodrin mRNA increased 5-fold. The exposure of cerebellar neurons to NMDA induced the accumulation of a 150 kd proteolytic fragment of fodrin. The NMDA-induced breakdown of fodrin was time-, concentration-, and Ca2(+)-dependent and was inhibited by APV, Mg2+, or the calpain I inhibitor N-acetyl-Leu-Leu-norleucinal. Kainate caused fodrin proteolysis through indirect activation of NMDA receptors. Quisqualate was ineffective. The NMDA-induced degradation of fodrin occurred under conditions that did not cause degeneration of cultured cerebellar neurons. These results show that Ca2+/calpain I-dependent proteolysis of fodrin is selectively associated with NMDA receptor activation; however, fodrin proteolysis per se does not play a causal role in NMDA-induced toxicity in cerebellar granule cells.

Glial cells of the oligodendrocyte lineage express both kainate- and AMPA-preferring subtypes of glutamate receptor.

mRNAs for AMPA- and kainate-preferring glutamate receptor subunits are expressed abundantly in the CNS, yet functional studies of neurons and glia from brain suggest selective expression of AMPA receptors. We now show that glial cells of the O-2A lineage express rapidly desensitizing responses to kainate, mRNAs for GluR6, GluR7, KA-1, and KA-2, rapidly desensitizing responses to AMPA, and mRNAs for GluR-B, -C, and -D. Analysis of glutamate receptor currents in single cells reveals two receptor populations with high and low affinity for kainate and different sensitivity for potentiation by concanavalin A and for block of desensitization by cyclothiazide. Our experiments describe the characterization of native kainate-preferring receptors in glia and reveal coexpression in single cells of functional AMPA- and kainate-preferring receptors.

Effects of faba beans with different concentrations of vicine and convicine on egg production, egg quality and red blood cells in laying hens.

The faba bean (Vicia faba L.) is a potential source of proteins for poultry, mainly for laying hens whose protein requirements are lower than those of other birds such as growing broilers and turkeys. However, this feedstuff contains anti-nutritional factors, that is, vicine (V) and convicine (C) that are already known to reduce laying hen performance. The aim of the experiment reported here was to evaluate the effects of a wide range of dietary V and C concentrations in laying hens. Two trials were performed with laying hens fed diets including 20% or 25% of faba bean genotypes highly contrasting in V+C content. In Trial 1, faba beans from two tannin-containing cultivars, but with high or low V+C content were dehulled in order to eliminate the tannin effect. In addition to the contrasting levels of V+C in the two cultivars, two intermediate levels of V+C were obtained by mixing the two cultivars (70/30 and 30/70). In Trial 2, two isogenic zero-tannin faba bean genotypes with high or low V+C content were used. In both trials, a classical corn-soybean diet was also offered to control hens. Each experimental diet was given to 48 laying hens for 140 (Trial 1) or 89 (Trial 2) days. Laying performance and egg quality were measured. The redox sensitivity of red blood cells (RBCs) was assessed by measuring hemolysis and reduced glutathione (GSH) concentration in these cells. Egg weight was significantly reduced by the diets containing the highest concentrations of V+C (P<0.0001) in Trial 1 and slightly reduced (P<0.10) in Trial 2, but only weak linear relationships between egg weight and dietary V+C concentration were established. No negative effect of V+C level was observed for egg quality parameters. In contrast, certain parameters (i.e. Haugh units, yolk color) were improved by feeding low V+C diets (P<0.05). Hemolysis of RBCs was higher in hens fed high V+C diets. A decrease in GSH concentration in RBCs of hens fed the highest levels of V+C was observed. Faba bean genotypes with low concentrations of V+C can therefore be used in laying hen diets up to 25% without any detrimental effects on performance levels or egg characteristics, without any risk of hemolysis of RBCs.

News on glutamate receptors in glial cells.

Glutamate (Glu) receptors convey most of the excitatory synaptic transmission in the mammalian CNS. Distinct Glu-receptor genes and different subtypes of glutamate-activated channels are expressed ubiquitously throughout the developing and mature brain in the two major macroglial cell types, astrocytes and oligodendrocytes. These glial receptors are found in acutely isolated cells and in brain slices, and are therefore functional in vivo. Glutamate receptors in glial cells are activated during neuronal activity, and their activation modulates gene expression in astrocytes and oligodendrocytes. The proliferation and differentiation of glial precursor cells are also regulated by activation of Glu receptors, suggesting that the excitatory transmitter might be one of the environmental signals that regulate glial-cell development.

Inhibition of cyclin E-cyclin-dependent kinase 2 complex formation and activity is associated with cell cycle arrest and withdrawal in oligodendrocyte progenitor cells.

Stimulatory and inhibitory signals regulate cell proliferation through the activity of specific enzymes that operate in distinct phases of the cell cycle. We have studied cell cycle progression, arrest, and withdrawal in the oligodendrocyte progenitor (OP) cell model system, focusing on the G(1) phase and G(1)-S transition. Not only were proliferating OPs found to display higher protein levels of cyclin E and D and cyclin-dependent kinases (cdk) 2, 4, and 6 than cells that had permanently withdrawn from the cycle, but the kinase activities of both cyclin D-cdk4/6 and cyclin E-cdk2 were also higher in dividing OPs. This was associated with a decrease in the formation of the cyclin E-cdk2 and cyclin D-cdk4/cyclin D-cdk6 complexes in differentiated oligodendrocytes that had permanently withdrawn from the cell cycle. Reversible cell cycle arrest in G(1) induced by glutamatergic and beta-adrenergic receptor activation or cell depolarization, however, did not modify cyclin E and cdk2 protein expression compared with proliferating OPs. Instead, these agents caused a selective decrease in cdk2 activity and an impairment of cyclin E-cdk2 complex formation. Although cyclin D protein levels were higher than in proliferating cells, cyclin D-associated kinase activity was not modified in G(1)-arrested OPs. Analysis in corpus callosum in vivo showed that cyclin E-cdk2 activity increased between postnatal days 3 and 15 and decreased between postnatal days 15 and 30. Our results indicate that the cyclin E-cdk2 complex is a major regulator of OP cell cycle progression and that the cdks involved in reversible cell cycle arrest are distinct from those implicated in permanent cell cycle withdrawal.

Stimulation of endothelin B receptors in astrocytes induces cAMP response element-binding protein phosphorylation and c-fos expression via multiple mitogen-activated protein kinase signaling pathways.

The vasoconstrictor peptide endothelin (ET-1) exerts its physiological and pathological effects via activation of ET(A) and ET(B) receptor (ET-R) subtypes. In this study, we demonstrate that both ET-R subtypes are highly expressed in rat astrocytes in vivo, indicating that these cells are potential targets of the biological effects of ET-1 in the brain. In cultured cortical astrocytes, both ET-R subtypes are expressed, and selective stimulation of ET(B)-R with ET-1 induces phosphorylation of cAMP response element-binding protein (CREB). The signal transduction pathway activated by ET-1 includes the Rap1/B-Raf and the Ras/Raf-1 complexes, protein kinase C (PKC) together with extracellular signal-regulated kinases (ERK), and the ribosomal S6 kinase (RSK) isoforms RSK2 and RSK3, two kinases that lie immediately downstream of ERK and are able to phosphorylate CREB. Moreover, ET-1 activates the p38 mitogen-activated protein kinase (MAPK)-dependent, but not the c-jun N-terminal kinase (JNK)-dependent pathway. By using selective protein kinase inhibitors and expression of dominant-negative Rap1 protein, we also found that the Rap1/PKC/ERK-dependent pathway induces the phosphorylation of activating transcription factor-1, CREB, and Elk-1, whereas the p38MAPK-dependent pathway only causes CREB phosphorylation. ET-1-induced transcription of the immediate early gene c-fos requires the concomitant activation of both the PKC/ERK- and p38MAPK-dependent pathways, because inhibitors of either pathway block the ET-1-induced increase of c-fos mRNA. Our findings indicate that changes in the expression of cAMP response element-dependent immediate and delayed response genes could play a pivotal role in the physiological effects elicited by ET-1 in astrocytes.

Glutamate receptors in glia: new cells, new inputs and new functions.

Functional glutamate receptors are expressed on the majority of glial cell types in the developing and mature brain. Although glutamate receptors on glia are activated by glutamate released from neurons, their physiological role remains largely unknown. Potential roles for these receptors in glia include regulation of proliferation and differentiation, and modulation of synaptic efficacy. Recent anatomical and functional evidence indicates that glutamate receptors on immature glia are activated through direct synaptic inputs. Therefore, glutamate and its receptors appear to be involved in a continuous crosstalk between neurons and glia during development and also in the mature brain.