Cerebral Venous Thrombosis in COVID-19: A New York Metropolitan Cohort Study.

BACKGROUND AND PURPOSE: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection is associated with hypercoagulability. We sought to evaluate the demographic and clinical characteristics of cerebral venous thrombosis among patients hospitalized for coronavirus disease 2019 (COVID-19) at 6 tertiary care centers in the New York City metropolitan area. MATERIALS AND METHODS: We conducted a retrospective multicenter cohort study of 13,500 consecutive patients with COVID-19 who were hospitalized between March 1 and May 30, 2020. RESULTS: Of 13,500 patients with COVID-19, twelve had imaging-proved cerebral venous thrombosis with an incidence of 8.8 per 10,000 during 3 months, which is considerably higher than the reported incidence of cerebral venous thrombosis in the general population of 5 per million annually. There was a male preponderance (8 men, 4 women) and an average age of 49 years (95% CI, 36-62 years; range, 17-95 years). Only 1 patient (8%) had a history of thromboembolic disease. Neurologic symptoms secondary to cerebral venous thrombosis occurred within 24 hours of the onset of the respiratory and constitutional symptoms in 58% of cases, and 75% had venous infarction, hemorrhage, or both on brain imaging. Management consisted of anticoagulation, endovascular thrombectomy, and surgical hematoma evacuation. The mortality rate was 25%. CONCLUSIONS: Early evidence suggests a higher-than-expected frequency of cerebral venous thrombosis among patients hospitalized for COVID-19. Cerebral venous thrombosis should be included in the differential diagnosis of neurologic syndromes associated with SARS-CoV-2 infection.

Middle Meningeal Artery Embolization Using Combined Particle Embolization and n-BCA with the Dextrose 5% in Water Push Technique for Chronic Subdural Hematomas: A Prospective Safety and Feasibility Study.

BACKGROUND AND PURPOSE: Embolization of the middle meningeal artery for treatment of refractory or recurrent chronic subdural hematomas has gained momentum during the past few years. Little has been reported on the use of the n-BCA liquid embolic system for middle meningeal artery embolization. We present the technical feasibility of using diluted n-BCA for middle meningeal artery embolization. MATERIALS AND METHODS: We sought to examine the safety and technical feasibility of the diluted n-BCA liquid embolic system for middle meningeal artery embolization. Patients with chronic refractory or recurrent subdural hematomas were prospectively enrolled from September 2019 to June 2020. The primary outcome was the safety and technical feasibility of the use of diluted n-BCA for embolization of the middle meningeal artery. The secondary end point was the efficacy in reducing hematoma volume. RESULTS: A total of 16 patients were prospectively enrolled. Concomitant burr-hole craniotomies were performed in 12 of the 16 patients. Two patients required an operation following middle meningeal artery embolization for persistent symptoms. The primary end point was met in 100% of cases in which there were no intra- or postprocedural complications. Distal penetration of the middle meningeal artery branches was achieved in all the enrolled cases. A 7-day post-middle meningeal artery embolization follow-up head CT demonstrated improvement (>50% reduction in subdural hematoma volume) in 9/15 (60%) patients, with 6/15 (40%) showing an unchanged or stable subdural hematoma. At day 21, available CT scans demonstrated substantial further improvement (>75% reduction in subdural hematoma volume). CONCLUSIONS: Embolization of the middle meningeal artery using diluted n-BCA and ethiodized oil (1:6) is safe and feasible from a technical standpoint. The use of a dextrose 5% bolus improves distal penetration of the glue.

Ultra-thin polarization independent broadband terahertz metamaterial absorber.

In this work, we present the design of a polarization independent broadband absorber in the terahertz (THz) frequency range using a metasurface resonator. The absorber comprises of three layers, of which, the top layer is made of a vanadium dioxide (VO2) resonator with an electrical conductivity of σ = 200000 S/m; the bottom layer consists of a planar layer made of gold metal, and a dielectric layer is sandwiched between these two layers. The optimized absorber exhibits absorption greater than 90% from 2.54-5.54 THz. Thus, the corresponding bandwidth of the designed absorber is 3 THz. Further, the thermal tunable absorption and reflection spectra have been analyzed by varying the electrical conductivity of VO2. The impact of the various geometrical parameters on the absorption characteristics has also been assessed. The physics of generation of broadband absorption of the proposed device has been explored using field analysis. Finally, the absorption characteristics of the unit cell has been studied for various incident and polarization angles.

Functional Immune Anatomy of the Liver-As an Allograft.

The liver is an immunoregulatory organ in which a tolerogenic microenvironment mitigates the relative "strength" of local immune responses. Paradoxically, necro-inflammatory diseases create the need for most liver transplants. Treatment of hepatitis B virus, hepatitis C virus, and acute T cell-mediated rejection have redirected focus on long-term allograft structural integrity. Understanding of insults should enable decades of morbidity-free survival after liver replacement because of these tolerogenic properties. Studies of long-term survivors show low-grade chronic inflammatory, fibrotic, and microvascular lesions, likely related to some combination of environment insults (i.e. abnormal physiology), donor-specific antibodies, and T cell-mediated immunity. The resultant conundrum is familiar in transplantation: adequate immunosuppression produces chronic toxicities, while lightened immunosuppression leads to sensitization, immunological injury, and structural deterioration. The "balance" is more favorable for liver than other solid organ allografts. This occurs because of unique hepatic immune physiology and provides unintended benefits for allografts by modulating various afferent and efferent limbs of allogenic immune responses. This review is intended to provide a better understanding of liver immune microanatomy and physiology and thereby (a) the potential structural consequences of low-level, including allo-antibody-mediated injury; and (b) how liver allografts modulate immune reactions. Special attention is given to the microvasculature and hepatic mononuclear phagocytic system.

A case of mixed connective tissue disease with pseudo-pseudo Meigs' syndrome (PPMS)-like features.

Pseudo-pseudo Meigs' syndrome (PPMS) has been reported to be a rare presentation of patients with systemic lupus erythematosus (SLE). However, such a presentation is not common in other forms of connective tissue disease. We presented a case of gross ascites, pleural effusion, and marked elevation of CA-125 level (PPMS-like features) that led to a diagnosis of MCTD. The patient responded to systemic steroid therapy.

ADAMTS13 modulates atherosclerotic plaque progression in mice via a VWF-dependent mechanism.

BACKGROUND: ADAMTS13 reduces the adhesiveness of hyperactive ultra-large von Willebrand factor (ULVWF) multimers by cleaving them into smaller, less active multimers. Recently, we and others have demonstrated that ADAMTS13 reduces atherosclerosis in hypercholesteremic apolipoprotein E (ApoE-/-) deficient mice. It is not known whether ADAMTS13 modulates atherosclerosis directly or indirectly by cleaving ULVWF multimers. OBJECTIVE: We generated triple knockout Adamts13-/-/Vwf-/-/ApoE-/- mice to determine whether ADAMTS13 modulates atherosclerosis through its proteolytic effects on VWF or other potential mechanisms. METHODS: Female mice were fed a high-fat Western diet beginning at 6 weeks of age until they were sacrificed at 4 months. We compared the extent of atherosclerosis in the serial cross-sections of the aortic sinus using the Verhoeff-Van Gieson stain. Macrophage and neutrophil infiltration were quantified by immunohistochemistry. Under plain polarized light interstitial collagen content in the serial cross-sections of the aortic sinus was quantified using picrosirius red stain. RESULTS: Deficiency of VWF in Adamts13-/-/ApoE-/- mice (Adamts13-/-/Vwf-/-/ApoE-/-) completely reversed exacerbated atherosclerosis (P < 0.05 vs. Adamts13-/-/ApoE-/- mice). The lesion size, macrophage and neutrophil infiltration in the aortic sinus of Adamts13-/-/Vwf-/-/ApoE-/- mice were significantly decreased compared with Adamts13-/-/ApoE-/- mice (P < 0.05), but similar to Vwf-/-/ApoE-/- mice. Additionally, interstitial collagen content in the aortic sinus of Adamts13-/-/Vwf-/-/ApoE-/- mice was significantly reduced compared with Adamts13-/-/ApoE-/- mice (P < 0.05), but similar to Vwf-/-/ApoE-/- mice. Total cholesterol and triglyceride levels were similar among groups. CONCLUSIONS: ADAMTS13 modulates inflammatory plaque progression in hypercholesterolemic mice through a VWF-dependent mechanism. These findings provide further evidence on the pathophysiological role for the ADAMTS13/VWF axis in atherosclerosis.

Current update on the endovascular management of intracranial aneurysms.

Rapid technological advances in the endovascular field has revolutionized the treatment of intracranial aneurysms. Since the Food and Drug Administration approval of Guglielmi detachable coils in 1995, a variety of newer coils with different design and physical properties such as complex coils, stretch resistant and bioactive coils, have become available promising to increase packing density and decrease aneurysmal recurrence and recanalization rates. Treatment of wide neck intracranial aneurysms has improved with availability of compliant balloons and newer intracranial assist devices. Emerging technology such as flow diverters hold promise in treatment of large and difficult to treat intracranial aneurysms. Liquid embolic agent (Onyx HD 500) offer a novel, safe and effective adjunctive treatment option when used in combination with coils with stent and/or balloon assist technique. Endovascular treatment options have vastly expanded the armamentarium of neurosurgeons allowing safe and durable treatment of aneurysms previously amenable to clipping only.

Endovascular therapy of acute ischemic stroke: report of the Standards of Practice Committee of the Society of NeuroInterventional Surgery.

OBJECTIVE: To summarize and classify the evidence for the use of endovascular techniques in the treatment of patients with acute ischemic stroke. METHODS: Recommendations previously published by the American Heart Association (AHA) (Guidelines for the early management of adults with ischemic stroke (Circulation 2007) and Scientific statement indications for the performance of intracranial endovascular neurointerventional procedures (Circulation 2009)) were vetted and used as a foundation for the current process. Building on this foundation, a critical review of the literature was performed to evaluate evidence supporting the endovascular treatment of acute ischemic stroke. The assessment was based on guidelines for evidence based medicine proposed by the Stroke Council of the AHA and the University of Oxford, Centre for Evidence Based Medicine (CEBM). Procedural safety, technical efficacy and impact on patient outcomes were specifically examined.

Society of NeuroInterventional Surgery Standards of Practice: general considerations.

This is the first in a set of documents intended to standardize techniques, procedures, and practices in the field of endovascular surgical neuroradiology. Standards are meant to define core practices for peer review, comparison, and improvement. Standards and guidelines also form the basic dialogue, reporting, and recommendations for ongoing practices and future development.

Microvascular decompression for trigeminal neuralgia: visualization of results in a 3D stereoscopic virtual reality environment.

BACKGROUND: This study employs 3D stereoscopic virtual reality technology to demonstrate the surgical results of microvascular decompression (MVD) for trigeminal neuralgia. PATIENTS/MATERIAL AND METHODS: 3D models were rendered by fusing CTA and MRI fast imaging employing steady state acquisition (FIESTA) modalities of both pre- and post-operative scans. The brainstem, trigeminal nerve root and relevant vasculature were extracted, superimposed, and co-registered to bony and ventricular anatomy. RESULTS: 3 clinically successful MVD cases were evaluated for superior cerebellar artery (SCA) vessel displacement. Qualitative parameters included translational and rotational shift of the SCA, and distance decompressed from the trigeminal nerve root entry zone. Parameters were met in each case, with demonstration of vessel displacement and decompression of the nerve root. CONCLUSION: The 3D virtual-reality environment with stereoscopic visualization offers a method through which to visualize the results of MVD, and a potential reference point to evaluate cases of treatment failure or relapse.

Clinical characteristics of gout: a hospital case series.

INTRODUCTION: Gout is an increasingly common medical problem. The traditional risk factors of male sex and high red meat or alcohol consumption have been joined with newer risks such as increased life expectancy, and the metabolic syndrome (hypertension, diabetes, dyslipidaemia, truncal obesity). METHODS: This was a retrospective study to determine the epidemiology, clinical features, associated conditions as well as renal related conditions in existing gout patients followed-up in Rheumatology outpatient clinic, Hospital Tuanku Ja'afar, Seremban. RESULTS: Over a three month period, we identified 54 gouty patients on our follow-up, the majority being male, Malay ethnicity, with the age of onset in the third and fourth decades of life. Commonly associated risk factors were hypertension, hyperlipidaemia and obesity. However, underlying history of diabetes mellitus, alcohol consumption, and family history were not commonly associated with gout in our group of patients. Half of our patients had at least two or more joints involvement. About half of the patients with tophaceous gout had renal impairment. CONCLUSION: Our series of gout patients highlight the high prevalence of cardiovascular risk factors. The high prevalence of tophi and renal impairment is a cause for concern.

Neurologic complications of inferior petrosal sinus sampling.

BACKGROUND AND PURPOSE: Inferior petrosal sinus sampling (IPSS) is a useful diagnostic technique in adrenocorticotropic hormone (ACTH)-dependent hypercortisolism with normal or equivocal MR imaging. The procedure is believed to be safe, with mostly minor complications. However, there are rare, but severe, neurologic complications that need to be considered. MATERIALS AND METHODS: We performed an institutional review board-approved retrospective review of our institutional IPSS experience from July 2001 to January 2007. IPSS was performed for the evaluation of Cushing disease. The end points of particular interest were the indications for IPSS and the incidence of associated complications. RESULTS: During the study period of 5(1/2) years, 44 patients underwent IPSS for evaluation of Cushing disease. There were 33 women and 11 men with a mean age of 43.1 years. Because of equivocal imaging and endocrine testing, 36 of 44 patients underwent IPSS, and 8 of 44 underwent IPSS after failed transsphenoidal exploration. The only complication was injury to the brain stem that occurred after an unremarkable procedure in a 42-year-old woman. She developed clinical evidence of pontomedullary dysfunction with MR imaging consistent with brain stem infarction. The cause of this injury is unclear, but a venous variant leading to transient venous hypertension or thrombosis is suspected. CONCLUSION: Neurologic injury is a rare but serious complication associated with IPSS. Despite this, if performed under a strict paradigm, IPSS is both accurate and safe and can be very useful in the management of Cushing disease.

Endothelin receptor antagonist TAK-044 arrests and reverses the development of carbon tetrachloride induced cirrhosis in rats.

BACKGROUND AND AIMS: Hepatic concentrations of the powerful vasoconstrictor and fibrogen endothelin 1 (ET-1) and its receptors increase in human and experimental cirrhosis, suggesting a major role for ET-1 in the pathology of chronic liver disease. We investigated whether ET-1 receptor antagonism, after the development of fibrosis and cirrhosis, arrests/reverses the progression of chronic liver disease. METHODS: Chronic liver injury was induced in rats by carbon tetrachloride (CCl(4)) treatment (0.15 ml/kg intraperitoneally twice a week) in conjunction with phenobarbital in drinking water (0.4 g/l) for four (group 1: fibrosis) and eight (group 2: cirrhosis) weeks. Rat were then treated concurrently with the ET-1 receptor antagonist TAK-044 (10 mg/kg/day) and CCl(4)/phenobarbital for a further four weeks. RESULTS: Histopathological examination revealed significant arrest of progression to cirrhosis in group 1 and reversal of cirrhosis in group 2 rats. TAK-044 treatment caused significant amelioration of portal hypertension, systemic hypotension, and liver injury (reduced activities of serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), and improved hepatic synthetic capacity (increased serum albumin concentration) in both groups of rats relative to vehicle treated rats. TAK-044 treatment reduced collagen synthesis, as evidenced by decreased hepatic hydroxyproline content, mRNA expression of collagen-alpha type I, and tissue inhibitors of matrix metalloproteinases 1 and 2, and mRNA and protein expression of a potent fibrogenic cytokine, transforming growth factor beta1. CONCLUSIONS: The results emphasise the role of ET-1 in the development of cirrhosis and strongly suggest that blockade of its actions can be a rational therapy for chronic liver disease and its complications.

Increased hepatic platelet activating factor (PAF) and PAF receptors in carbon tetrachloride induced liver cirrhosis.

BACKGROUND AND AIMS: The liver is a major site for the synthesis and actions of platelet activating factor (PAF), a potent hepatic vasoconstrictor and systemic vasodilator. As PAF is implicated in portal hypertension and hyperdynamic circulation associated with liver cirrhosis, we characterised changes in the hepatic PAF system in experimental cirrhosis. METHODS: In rats made cirrhotic by carbon tetrachloride (CCl(4)) administration for eight weeks, we determined hepatic levels of PAF and its cognate receptor, and the effects of PAF and PAF antagonist (BN52021) on portal and arterial pressure. RESULTS: Compared with control rats, cirrhotic rats had higher hepatic PAF levels, higher apparent hepatic efflux of PAF, and higher PAF levels in arterial blood (p<0.01, p<0.01, p<0.05, respectively). Relative to controls, cirrhotic livers had elevated hepatic PAF receptors (by mRNA and protein levels and [(3)H]PAF binding), higher (p<0.01) baseline hepatic portal pressure, and an augmented (p = 0.03) portal pressure response to PAF infusion (1 microg/kg). Portal infusion of BN52021 (5 mg/kg) showed that elevated endogenous PAF was responsible for 23% of the cirrhotic portal pressure increase but made no contribution to systemic hypotension. Finally, increased PAF receptor density was observed in the contractile perisinusoidal stellate cells isolated from cirrhotic livers relative to those from control livers. CONCLUSIONS: In cirrhosis, increased hepatic release of PAF elevates systemic PAF; in combination with upregulated hepatic PAF receptors in stellate cells, this contributes to portal hypertension.

The role of the hippocampus in trace conditioning: temporal discontinuity or task difficulty?

It is well established that the hippocampal formation is critically involved in the acquisition of trace memories, a paradigm in which the conditioned (CS) and unconditioned stimuli (US) are separated by a temporal gap (Solomon et al., 1986). The structure is reportedly not critical for the acquisition of delay memories, where the CS and the US overlap in time (Berger & Orr, 1983; Schmaltz & Theios, 1972). Based on these results, it is often stated that the hippocampus is involved in "filling the gap" or otherwise associating the two stimuli in time. However, in addition to the presence of a temporal gap, there are other differences between trace and delay conditioning. The most apparent difference is that animals require many more trials to learn the trace task, and thus it is inherently more difficult than the delay task. Here, we tested whether the hippocampus was critically involved in delay conditioning, if it was rendered more difficult such that the rate of acquisition was shifted to be analogous to trace conditioning. Groups of rats received excitotoxic lesions to the hippocampus, sham lesions or were left intact. Using the same interstimulus intervals (ISI), control animals required more trials to acquire the trace than the delay task. As predicted, animals with hippocampal lesions were impaired during trace conditioning but not delay conditioning. However, when the delay task was rendered more difficult by extending the ISI (a long delay task), animals with hippocampal lesions were impaired. In addition, once the lesioned animal learned the association between the CS and the US during delay conditioning, it could learn and perform the trace CR. Thus, the role of the hippocampus in classical conditioning is not limited to learning about discontiguous events in time and space; rather the structure can become engaged simply as a function of task difficulty.

Association of CAG repeat loci on chromosome 22 with schizophrenia and bipolar disorder.

Chromosome 22 has been implicated in schizophrenia and bipolar disorder in a number of linkage, association and cytogenetic studies. Recent evidence has also implicated CAG repeat tract expansion in these diseases. In order to explore the involvement of CAG repeats on chromosome 22 in these diseases, we have created an integrated map of all CAG repeats > or =5 on this chromosome together with microsatellite markers associated with these diseases using the recently completed nucleotide sequence of chromosome 22. Of the 52 CAG repeat loci identified in this manner, four of the longest repeat stretches in regions previously implicated by linkage analyses were chosen for further study. Three of the four repeat containing loci, were found in the coding region with the CAG repeats coding for glutamine and were expressed in the brain. All the loci studied showed varying degrees of polymorphism with one of the loci exhibiting two alleles of 7 and 8 CAG repeats. The 8-repeat allele at this locus was significantly overrepresented in both schizophrenia and bipolar patient groups when compared to ethnically matched controls, while alleles at the other three loci did not show any such difference. The repeat lies within a gene which shows homology to an androgen receptor related apoptosis protein in rat. We have also identified other candidate genes in the vicinity of this locus. Our results suggest that the repeats within this gene or other genes in the vicinity of this locus are likely to be implicated in bipolar disorder and schizophrenia.

Down-regulation and recovery of endothelin-1 binding and signaling in rat cardiomyocytes.

Down-regulation and recovery of endothelin (ET) receptors and of ET-dependent phosphoinositide-specific phospholipase C (PI-PLC) signaling was examined in cultured cardiomyocytes from neonatal rats. Three hours treatment with 5 nM ET-1 decreased surface receptors to 30%, and transduction to 19%, of their respective time-zero values. After extensive washing and a 3 h recovery period surface receptors returned to 74% of the time-zero value, with concomitant recovery of signal transduction to 75% of the time-zero value. The recovery of PI-PLC signaling in these cells is in contrast with a previous report, but consistent with recovery of the receptor complement.

Inhibition of DNA synthesis in cultured hepatocytes by endotoxin-conditioned medium of activated stellate cells is transforming growth factor-beta and nitric oxide-independent.

Activated hepatic stellate cells play a major role in the pathophysiology of chronic liver disease. They can influence the metabolism of hepatocytes by producing a variety of cytokines and growth factors. Upon stimulation with endotoxin, stellate cells also synthesize nitric oxide (NO), a potent mediator of growth of several cell types including hepatocytes. We investigated the effect of serum-free medium conditioned by activated stellate cells in the absence and presence of endotoxin on NO and DNA synthesis in hepatocytes. Stellate cells and hepatocytes were isolated by enzymatic digestion of the liver. Stellate cells were cultured for 10 days after which the majority exhibited alpha-smooth muscle actin (a marker for activated cells); hepatocytes were used after overnight culture. While the medium conditioned by stellate cells in the absence of endotoxin stimulated DNA synthesis in hepatocytes, medium conditioned in its presence inhibited this process in an endotoxin concentration-dependent manner (10 - 1000 ng ml(-1)). Endotoxin-conditioned stellate cell medium also stimulated NO synthesis in hepatocytes; the effect was consistent with increased protein and mRNA expression of inducible NO synthase (iNOS). However, inhibition of DNA synthesis in hepatocytes caused by endotoxin-conditioned stellate cell medium was unaffected by the NOS inhibitor, L-N(G)-monomethylarginine (L-NMMA), guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and neutralizing antibodies for TGF-beta, IL-1beta, IL-6 and TNF-alpha. These results indicate that factors other than these cytokines produced by activated stellate cells upon stimulation with endotoxin or by hepatocytes challenged with endotoxin-conditioned stellate cell medium inhibit DNA synthesis in hepatocytes.

Receptor-stimulated phospholipase A(2) liberates arachidonic acid and regulates neuronal excitability through protein kinase C.

Type B photoreceptors in Hermissenda exhibit increased excitability (e.g., elevated membrane resistance and lowered spike thresholds) consequent to the temporal coincidence of a light-induced intracellular Ca(2+) increase and the release of GABA from presynaptic vestibular hair cells. Convergence of these pre- and postsynaptically stimulated biochemical cascades culminates in the activation of protein kinase C (PKC). Paradoxically, exposure of the B cell to light alone generates an inositol triphosphate-regulated rise in diacylglycerol and intracellular Ca(2+), co-factors sufficient to stimulate conventional PKC isoforms, raising questions as to the unique role of synaptic stimulation in the activation of PKC. GABA receptors on the B cell are coupled to G proteins that stimulate phospholipase A(2) (PLA(2)), which is thought to regulate the liberation of arachidonic acid (AA), an "atypical" activator of PKC. Here, we directly assess whether GABA binding or PLA(2) stimulation liberates AA in these cells and whether free AA potentiates the stimulation of PKC. Free fatty-acid was estimated in isolated photoreceptors with the fluorescent indicator acrylodan-derivatized intestinal fatty acid-binding protein (ADIFAB). In response to 5 microM GABA, a fast and persistent increase in ADIFAB emission was observed, and this increase was blocked by the PLA(2) inhibitor arachidonyltrifluoromethyl ketone (50 microM). Furthermore, direct stimulation of PLA(2) by melittin (10 microM) increased ADIFAB emission in a manner that was kinetically analogous to GABA. In response to simultaneous exposure to the stable AA analogue oleic acid (OA, 20 microM) and light (to elevate intracellular Ca(2+)), B photoreceptors exhibited a sustained (>45 min) increase in excitability (membrane resistance and evoked spike rate). The excitability increase was blocked by the PKC inhibitor chelerythrine (20 microM) and was not induced by exposure of the cells to light alone. The increase in excitability in the B cell that followed exposure to light and OA persisted for > or =90 min when the pairing was conducted in the presence of the protein synthesis inhibitor anisomycin (1 microm), suggesting that the synergistic influence of these signaling agents on neuronal excitability did not require new protein synthesis. These results indicate that GABA binding to G-protein-coupled receptors on Hermissenda B cells stimulates a PLA(2) signaling cascade that liberates AA, and that this free AA interacts with postsynaptic Ca(2+) to synergistically stimulate PKC and enhance neuronal excitability. In this manner, the interaction of postsynaptic metabotropic receptors and intracellular Ca(2+) may serve as the catalyst for some forms of associative neuronal/synaptic plasticity.