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Background: Alcohol use, especially at high consumption levels, can lead to irrational decision-making. In humans, this can lead to harmful outcomes often seen in the context of driving under the influence and or aggressive behavior. To date, the field is lacking comprehensive animal models to examine the impact of alcohol use on decision making in rodents, particularly to examine sex differences in choice behavior. To address this issue, the present study examined the effects of acute alcohol consumption during a behavioral approach-avoidance task that captures momentary changes in decision-making behavior and choice selection in female and male rats., Methods: Our team has developed a novel behavioral protocol involving a concurrent choice to consume four different concentrations of alcohol and sucrose combinations. During the task, female or male rats can approach or avoid drinking solutions in four distinct corners of our test apparatus. The solutions were prepared in inverse concentrations (higher sucrose was paired with lower alcohol and vice versa) so that the rodents pursue minimal alcohol use by consuming the higher sucrose concentrations or higher concentrations of alcohol by drinking the lower sucrose concentrations. The animals also have the option to avoid drinking alcohol by not approaching any of the drinking cups. Behavior and choice were tracked during task performance involving different solution concentrations of alcohol and sucrose., Results: The choice of consuming different concentrations of alcohol or sucrose resulted in sex-dependent differences in an approach-avoid trade-off pattern of behavior that was sensitive to different concentrations of alcohol/sucrose combinations. Notably, males were greatly affected by the introduction of alcohol into the task environment, approaching higher alcohol concentrations significantly more often than the non-alcohol containing options. In contrast, females choice patterns and task performance were largely unchanged during alcohol and non-alcohol containing tasks. Regardless of sex, we identify a novel method for identifying individual subject decision-making abnormalities during and after alcohol consumption., Conclusions: This research reveals a novel approach for examining the effects of acute alcohol exposure during a trade-off task, with decision patterns being more impacted by alcohol use in males as compared to females. We also offer the field a novel approach for identifying individual abnormalities in decision making behavior with the presentation of alcohol. Future research can explore these abnormal patterns in both acute and chronic alcohol conditions to develop methods for identifying subjects at-risk for developing an alcohol use disorder and the deleterious impact of alcohol on rational decision making.

Decision-making requires continuous adaptation to internal and external contexts. Changes in decision-making are reliable transdiagnostic symptoms of neuropsychiatric disorders. We created a computational model demonstrating how the striosome compartment of the striatum constructs a mathematical space for decision-making computations depending on context, and how the matrix compartment defines action value depending on the space. The model explains multiple experimental results and unifies other theories like reward prediction error, roles of the direct versus indirect pathways, and roles of the striosome versus matrix, under one framework. We also found, through new analyses, that striosome and matrix neurons increase their synchrony during difficult tasks, caused by a necessary increase in dimensionality of the space. The model makes testable predictions about individual differences in disorder susceptibility, decision-making symptoms shared among neuropsychiatric disorders, and differences in neuropsychiatric disorder symptom presentation. The model reframes the role of the striosomal circuit in neuroeconomic and disorder-affected decision-making., Highlights: Striosomes prioritize decision-related data used by matrix to set action values. Striosomes and matrix have different roles in the direct and indirect pathways. Abnormal information organization/valuation alters disorder presentation. Variance in data prioritization may explain individual differences in disorders., Etoc: Beck et al. developed a computational model of how a striatal circuit functions during decision-making. The model unifies and extends theories about the direct versus indirect pathways. It further suggests how aberrant circuit function underlies decision-making phenomena observed in neuropsychiatric disorders.

Translational studies benefit from experimental designs where laboratory organisms use human-relevant behaviors. One such behavior is decision-making, however studying complex decision-making in rodents is labor-intensive and typically restricted to two levels of cost/reward. We design a fully automated, inexpensive, high-throughput framework to study decision-making across multiple levels of rewards and costs: the REward-COst in Rodent Decision-making (RECORD) system. RECORD integrates three components: 1) 3D-printed arenas, 2) custom electronic hardware, and 3) software. We validated four behavioral protocols without employing any food or water restriction, highlighting the versatility of our system. RECORD data exposes heterogeneity in decision-making both within and across individuals that is quantifiably constrained. Using oxycodone self-administration and alcohol-consumption as test cases, we reveal how analytic approaches that incorporate behavioral heterogeneity are sensitive to detecting perturbations in decision-making. RECORD is a powerful approach to studying decision-making in rodents, with features that facilitate translational studies of decision-making in psychiatric disorders., (© 2024. The Author(s).)

Effective evaluation of costs and benefits is a core survival capacity that in humans is considered as optimal, "rational" decision-making. This capacity is vulnerable in neuropsychiatric disorders and in the aftermath of chronic stress, in which aberrant choices and high-risk behaviors occur. We report that chronic stress exposure in rodents produces abnormal evaluation of costs and benefits resembling non-optimal decision-making in which choices of high-cost/high-reward options are sharply increased. Concomitantly, alterations in the task-related spike activity of medial prefrontal neurons correspond with increased activity of their striosome-predominant striatal projection neuron targets and with decreased and delayed striatal fast-firing interneuron activity. These effects of chronic stress on prefronto-striatal circuit dynamics could be blocked or be mimicked by selective optogenetic manipulation of these circuits. We suggest that altered excitation-inhibition dynamics of striosome-based circuit function could be an underlying mechanism by which chronic stress contributes to disorders characterized by aberrant decision-making under conflict. VIDEO ABSTRACT., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To assess the utility of cost-effective dried blood spot (DBS) field sampling for incidence and drug resistance surveillance of persons at high risk for HIV infection., Methods: We evaluated DBS collected in 2007-2010 in non-clinical settings by finger-stick from HIV-positive heterosexuals at increased risk of HIV infection (n = 124), men who have sex with men (MSM, n = 110), and persons who inject drugs (PWID, n = 58). Relative proportions of recent-infection findings among risk groups were assessed at avidity index (AI) cutoffs of ≤25%, ≤30%, and ≤35%, corresponding to an infection mean duration of recency (MDR) of 220.6, 250.4, and 278.3 days, respectively. Drug resistance mutation prevalence was compared among the risk groups and avidity indices., Results: HIV antibody avidity testing of all self-reported ARV-naïve persons (n = 186) resulted in 9.7%, 11.3% and 14.0% with findings within the 221, 250, and 278-day MDRs, respectively. The proportion of ARV-naïve MSM, heterosexuals, and PWID reporting only one risk category who had findings below the suggested 30% AI was 23.1%, 6.9% and 3.6% (p<0.001), respectively. MSM had the highest prevalence of drug resistance and the only cases of transmitted multi-class resistance. Among the ARV-experienced, MSM had disproportionately more recent-infection results than did heterosexuals and PWID., Conclusions: The disproportionately higher recent-infection findings for MSM as compared to PWID and heterosexuals increased as the MDR window increased. Unreported ARV use might explain greater recent-infection findings and drug resistance in this MSM population. DBS demonstrated utility in expanded HIV testing; however, optimal field handling is key to accurate recent-infection estimates.

A universal need in understanding complex networks is the identification of individual information channels and their mutual interactions under different conditions. In neuroscience, our premier example, networks made up of billions of nodes dynamically interact to bring about thought and action. Granger causality is a powerful tool for identifying linear interactions, but handling nonlinear interactions remains an unmet challenge. We present a nonlinear multidimensional hidden state (NMHS) approach that achieves interaction strength analysis and decoding of networks with nonlinear interactions by including latent state variables for each node in the network. We compare NMHS to Granger causality in analyzing neural circuit recordings and simulations, improvised music, and sociodemographic data. We conclude that NMHS significantly extends the scope of analyses of multidimensional, nonlinear networks, notably in coping with the complexity of the brain.

Misconceptions about HIV transmission and prevention may inhibit individuals' accurate assessment of their level of risk. We used venue-based sampling to conduct a cross-sectional study of heterosexually active adults (N = 1,221) within areas exhibiting high poverty and HIV/AIDS rates in Miami-Dade and Broward counties in 2007. Two logistic regression analyses identified correlates of holding inaccurate beliefs about HIV transmission and prevention. Belief in incorrect HIV prevention methods (27.2%) and modes of transmission (38.5%) was common. Having at least one incorrect prevention belief was associated with being Hispanic compared to white (non-Hispanic), being depressed, and not knowing one's HIV status. Having at least one incorrect transmission belief was associated with being younger, heavy alcohol use, being depressed, not having seen a physician in the past 12 months, and not knowing one's HIV status. Among low-income heterosexuals, HIV prevention and transmission myths are widespread. Debunking them could have HIV prevention value.

The U.S. HIV/AIDS epidemic disproportionately impacts lower-income populations. We conducted a cross-sectional study of heterosexually active adults (N = 1076) in areas with high poverty and HIV/AIDS rates in South Florida in 2007. Using venue-based sampling, anonymous interviews and HIV tests were conducted at randomly selected venues (primarily retail businesses not associated with risk behaviors). The sample's HIV infection rate was 7.1%. Half (52.2%) of the infections were previously undiagnosed. Our findings underscore the impact of social and environmental factors on HIV risk, as well as the need to increase and optimize HIV testing and other prevention services.

Using data collected through venue-based sampling in South Florida from 2004 to 2005 as part of the Centers for Disease Control and Prevention-funded National HIV Behavioral Surveillance Among Men Who Have Sex with Men, we estimate the prevalence of crystal methamphetamine use and its association with high-risk sexual behaviors among a large and diverse sample of men who have sex with men (MSM) residing in South Florida. We also examine how these associations differ between HIV-positive and HIV-negative men. Bivariate analyses were used to assess the characteristics of study participants and their sexual risk behaviors by drug use and self-reported HIV status group. Of 946 MSM participants in South Florida, 18% reported crystal methamphetamine use in the past 12 months. Regardless of self-reported HIV status, crystal methamphetamine users were more likely to report high-risk sexual behaviors, an increased number of non-main sex partners, and being high on drugs and/or alcohol at last sex act with a non-main partner. Our findings indicate that crystal methamphetamine use is prevalent among the MSM population in South Florida, and this prevalence rate is similar, if not higher, than that found in US cities that have been long recognized for having a high rate of crystal methamphetamine use among their MSM populations. Notably, the use of crystal methamphetamine among both HIV-positive and HIV-negative MSM is associated with increased HIV-related risk behaviors.

Using in vitro techniques, we have shown that astrocytes do not increase the ouabain-sensitive Na(+)-K(+)-ATPase activity in cerebral endothelial cells. However, malignant astrocytoma cells when co-cultured with cerebral endothelial cells significantly enhance ouabain-sensitive Na(+)-K(+)-ATPase activity in cerebral endothelial cells. Also, Na(+)-K(+)-ATPase activity in cerebral endothelial cells co-cultured with malignant astrocytoma cells is inhibited by corticosteroids to the same degree as ouabain. These results suggest that brain edema associated with malignant glioma may in part be due to an increase in ouabain-sensitive Na(+)-K(+)-ATPase activity at the blood-brain barrier and that the antiedema effects of corticosteroids may be due to a reduction in the activity of this enzyme.

A series of 12 patients with mass lesions arising from Meckel's cave is presented. Patients' age on presentation ranged from 13 months to 71 years. Nine of the 12 patients had symptoms referable to the fifth cranial nerve, but only three complained of facial pain. The 12 patients presented eight different pathological entities, including meningioma, lipoma, schwannoma, malignant melanotic schwannoma, arachnoid cyst, neurofibroma, epidermoid tumor, and chordoma. Computerized tomography and magnetic resonance imaging were most useful in localizing the lesion to Meckel's cave. All 12 patients underwent a subtemporal approach to the lesion, and gross total removal was achieved in 11. Postoperative results were excellent with no increased neurological deficits seen 3 months postoperatively. Most patients had resolution of the cranial nerve deficits except for fifth nerve function, which was impaired in nine patients postoperatively. This series demonstrates that lesions in Meckel's cave can have a varied and unusual presentation, as well as an assortment of pathology. Total removal of lesions in this area resulted in relief of symptoms in most patients, with minimum morbidity.

In 58 patients with progressive neurological deterioration from angiographically confirmed cerebral vasospasm after spontaneous subarachnoid hemorrhage, arterial hypertension was induced in an attempt to improve their deficits. The most effective regimen consisted of intravascular volume expansion, blockade of the vagal depressor response, and the administration of antidiuretics and vasopressor agents. With this protocol, arterial blood pressure could be sustained at high levels for prolonged periods. Neurological deterioration was reversed in 47 patients, transiently in 4; permanent improvement occurred in 43. Complications experienced during therapy included pulmonary edema, dilutional hyponatremia, aneurysmal rebleeding, coagulopathy, hemothorax, and myocardial infarction. Elevating systemic arterial pressure in states of cerebrovascular insufficiency resulting from vasospasm is safe if meticulous attention is paid to physiological, biochemical, and hematological parameters, with the exception that it may be hazardous in the presence of an untreated ruptured or intact aneurysm. Intravascular volume expansion and induced hypertension are effective in reversing ischemic deficits from vasospasm provided that treatment commences before cerebral infarction and that adequate pressures are maintained for a sufficient period. The production of a hypervolemic state by the use of colloid and crystalloid infusion accompanied by atropine blockade of the vagal depressor response and blunting of the diuresis with vasopressin enables arterial pressure to be elevated for longer than 1 week.

Although macrophages are the earliest cells found in association with vessels in an area of cerebral injury, the role of this cell in the subsequent regeneration of the microvasculature is unknown. DNA synthesis in cerebral endothelial cells at the margin of injury of mouse brain was assayed by quantitation of the labeling indices from 3H-thymidine autoradiographs of normal animals and animals with X-ray-induced leukopenia. A mean endothelial cell labeling index of 10% in the irradiated animals was significantly lower than control animals (26.7%) (p less than 0.01). In vitro tissue culture studies utilizing peritoneal macrophages and cerebral endothelium were then used to isolate the endothelial response to macrophages and their products. Macrophage-conditioned media did not stimulate cerebral endothelial proliferation when evaluated by a growth factor assay, although this macrophage-conditioned media did stimulate DNA synthesis in fibroblasts and bovine aortic endothelium. A migration study of the cerebral endothelial cells utilizing an agarose technique showed enhanced random migration in the presence of macrophage-conditioned media compared to controls (p less than 0.01). The results indicate that macrophages do not directly stimulate proliferation of cerebral endothelial cells, but influence their migration. A loss of contact inhibition and subsequent DNA synthesis and replication may follow.

We evaluated 95 hospitalized patients (50 women and 45 men) aged 15 to 45 who had nontraumatic subarachnoid hemorrhage (SAH). Aneurysmal SAH was identified in 75 patients. Other causes for SAH were ruptured arteriovenous malformations (2 cases), amphetamine arteritis (1 case), and leptomeningeal melanoma (1 case). The cause of SAH was undetermined in 16 (17%) patients. Thirteen patients had histories of hypertension, 5 used oral contraceptives, and 4 had consumed large quantities of alcohol during the day before SAH. Only 1 patient had Type I diabetes mellitus. Diagnosis was delayed in 21 patients. Operation was performed in 71 patients, with only 3 (4.2%) deaths. The overall mortality was 8.4% (8 of 95), with all deaths due to neurological causes. Our data suggest that the overall management and surgical results of treatment of ruptured aneurysms in young adults are excellent, diabetes is rare among young adults with SAH, recent alcohol consumption does not seem to be a major factor predisposing to SAH in young adults, and misinterpretation of the early symptoms of SAH continues to be a serious problem.

A giant aneurysm of the vertebro-basilar junction is reported. It was successfully treated by ligation of the left vertebral artery, temporary occlusion of the right vertebral and basilar arteries, and evacuation of the aneurysm, following which the neck of the aneurysm was clipped.

Experiments were performed to test the hypothesis that insulin stimulates DNA synthesis in cerebral microvessel endothelium and smooth muscle. Cultured endothelium and smooth muscle derived from isolated mouse cerebral microvessels were exposed to insulin in serum-free medium, and [3H]-thymidine incorporation in the cells was measured. Up to 40-fold stimulation of DNA synthesis in endothelium and fourfold stimulation in smooth muscle were observed. Stimulation became maximal in both cell types at an insulin concentration of approximately 10(4) ng/ml, although an effect was observed at much lower concentrations. Similar concentrations of insulin produced a less-dramatic (approximately twofold) increase in both endothelial and smooth muscle cell numbers. This effect of insulin, observed in microvessel endothelium and smooth muscle, but not in bovine aortic endothelium, emphasizes another way in which large- and small-vessel endothelia appear to differ.

Adenosine uptake by cerebral smooth muscle cells is a carrier-mediated process. The Km value for adenosine uptake is 10.0 microM and the Vmax is 0.95 nmol/min-mg cell protein. This uptake system is inhibited by the adenosine analog 2-chloroadenosine at low adenosine concentrations. These results prove the existence of a nucleoside transport system associated with cerebral smooth muscle.

Cerebral water content is a variable quantity subject to the influence of hemodynamic and biochemical factors. Corticosteroids are frequently used in the therapy of cerebral edema, although their mechanisms of action in promoting the resolution of this state of pathologically increased water content remains unclear. To investigate this, a modified Ussing chamber was designed. The bulk flow of media (mainly composed of water) across a monolayer of cultured mouse cerebral endothelia was measured as a control. The same membranes were then exposed to either micromolar concentrations of hydrocortisone or methylprednisolone. The hydraulic conductivity (Lp) of each membrane before and after exposure to the corticosteroids was calculated as a reflection of membrane tightness. Methyl-prednisolone decreased the Lp of the membrane (i.e. tightened) by 36.1% compared to control. Hydrocortisone actually increased Lp (i.e. loosened the membrane) but not to a significant extent. The decrease in the bulk flow caused by methylprednisolone in vitro suggests that the mechanism of the clinically observed decrease in cerebral edema after corticosteroid administration may be due to the reduction of bulk flow across the blood-brain barrier.

Meningiomas have been hypothesized as being hormonally sensitive on the basis of epidemiologic, clinical, and laboratory evidence. Eight meningiomas were assayed and found to have androgen-binding protein. Three tumors were subjected to in vitro growth studies in varying concentrations of dihydrotestosterone (DHT). The growth of tumor 1 was unaltered. Tumor 2 demonstrated 9% to 10% growth (P less than 0.05) in all concentrations tested. Tumor 3 revealed an 11% stimulation, but only in the lowest concentration of DHT tested. The small quantity, saturability, and in one tumor, high binding affinity, suggest this binding protein is a receptor. The in vitro response of these meningiomas was small and was not dose-related or proportionate to receptor quantity. Androgens do not appear to play as important a role as progesterone or estrogen in meningioma growth in vitro.

An intrinsic coagulation pathway inhibitor with acitivty against factor XI was detected in the plasma of a 3-year-old child, following a respiratory infection. The inhibitor was present transiently, but it was clinically significant and was manifiested by extensive bruises. Abnormalities of clotting and the bruising tendency disappeared simultaneously without treatment before the inhibitor could be definitively characterized. It was possibly the consequence of an adenovirus infection, as an elevated adenovirus titer was demonstrated in the patient's blood. It is possible that inhibitors of this type are more common sequelae of viral infections than realized, and perhaps a systematic effort should be made to detect them and to define their etiology and mechanism of action.

Antifibrinolytic drugs reduce the risk of rebleeding during the first 2 weeks after aneurysmal subarachnoid hemorrhage. However, they do not lower overall mortality, largely because of an increased incidence of cerebral ischemia. The usefulness of antifibrinolytic drugs might be increased if a method to prevent or control vasospasm in patients were to be developed. We recently completed late Phase I and Phase II studies of the calcium ion blocking drug nicardipine in 67 patients treated within 1 week of subarachnoid hemorrhage. Of these 67 patients, 42 had delayed operations and were treated concomitantly with the antifibrinolytic drug aminocaproic acid (1.5 g/hr) for an average of 6 days before surgery. The outcome of these 42 patients is the subject of this report. Fifteen of 42 patients were treated with the lower dosage levels of nicardipine (0.4-4.5 mg/m2/hr), and 27 patients were treated at the highest dosage level (6.0 mg/m2/hr). Using the World Federation of Neurological Surgeons scale for subarachnoid hemorrhage, at admission 18 patients were Grade I, 15 were Grade II, 6 were Grade III, and 3 were Grade IV. Five patients (12%) developed clinical signs of deterioration suggestive of cerebral ischemia with concomitant evidence of vasospasm on arteriography. These patients were all treated with hypervolemic hypertensive therapy. Only one patient (2%) developed an infarction from vasospasm. Two patients developed symptomatic hydrocephalus requiring ventriculoperitoneal shunting, and a third patient required a temporary ventriculostomy. The 3-month postoperative outcomes were excellent. Three patients (7%) rebled. Three patients died, two from rebleeding of the aneurysm and one who never regained consciousness from the initial hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

The diagnosis of intracranial epidermoid tumors with computed tomography (CT) is often difficult because of indistinct margins, close proximity to the skull base, and a density similar to that of cerebrospinal fluid (CSF). Recent experience with six histologically confirmed epidermoid tumors served to emphasize the value of magnetic resonance (MR) imaging in studying these lesions. MR images were obtained using varying spin echo and inversion recovery techniques with a 0.5-tesla superconducting magnet. CT with and without enhancement had been performed in each case. In Case 1, CT showed an ill-defined left cerebellopontine angle hypodensity. MR imaging clearly showed the presence of abnormal tissue at that location. Case 2 showed a CSF density mass in the right upper posterior fossa. MR imaging of that area showed a variegated signal of a mass extending supratentorially. CT of Case 3 showed a left medial middle fossa hypodensity with an enhancing rim. MR imaging showed a clearly extraaxial mass in that location. In Case 4, a diffuse cerebellar hemispheric hypodensity was observed on CT and was clearly demarcated by MR studies. A huge lesion, thought initially to be an arachnoid cyst on CT of Case 5, was seen on MR imaging to be a large, extraventricular mass displacing the temporal lobe. Finally, CT in Case 6 was suggestive of a poorly demarcated right cerebellopontine angle lesion, which was seen on MR images to be extraaxial, displacing the brain stem. Various MR images more clearly demonstrate the extent of abnormal tissue than CT of epidermoid tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Polarity has been shown to exist at the blood-brain barrier (BBB) with respect to Na+-dependent neutral amino acid transport. A situation similar to the endothelial-astrocyte relationship existing at the BBB can be produced by growing cultured cerebral endothelium on one side of a filter and C6 glial cells on the other in an enclosed double chamber. In this setting 3H-alpha-methylaminoisobutyric acid transport can be demonstrated and is more rapid from the glial surface across the endothelium, as compared with transport in the opposite direction. The observation supports a glial influence on BBB polarity in this system.

Continuous cerebrospinal fluid (CSF) drainage may be used in the treatment CSF fistula. The procedure, however, is not without risk. Marked gradients between the intracranial and intraspinal CSF pressures and intravasation of air through an unsealed fistula may produce serious neurological problems. The use of continuous CSF drainage requires an alert, informed nursing staff to avert catastrophe.

Heparin and heparin fragments in combination with corticosteroids have been shown to markedly inhibit tumor angiogenesis. Experiments were performed to test the hypothesis that heparin, heparin fragments, and the combination of heparin and corticosteroids affect DNA synthesis and the proliferation of cerebral microvessel endothelium (ME). In vitro, methyl-3H-thymidine incorporation in the ME cells was measured after a 24 hour pulse. Our results show that heparin, hydrocortisone, and heparin in combination with hydrocortisone had a slight inhibitory effect on DNA synthesis of ME (p less than 0.05), and hydrocortisone in combination with heparin had a slight inhibitory effect on ME cell growth (p less than 0.05). The hexa-, octa-, and deca-saccharide fragments of heparin stimulated DNA synthesis in ME (p less than 0.01). In vivo, DNA synthesis in cerebral endothelial cells at the margin of a freeze lesion to mouse cerebral cortex was assayed by quantitation of labeling indexes from methyl-3H-thymidine autoradiographs in mice treated with heparin, cortisone, or a combination of heparin and cortisone. A mean endothelial cell labeling index (LI) of 6% in the cortisone-treated animals was significantly lower than controls (32%, p less than 0.01). The addition of heparin to cortisone did not significantly alter the endothelial cell LI compared to the cortisone-treated animals, and heparin alone did not significantly alter the LI compared to the controls. These results indicate that cortisone markedly reduces the endothelial proliferation around a cortical freeze lesion in vivo. This effect is independent of heparin.

A retrospective study was performed to evaluate the efficacy of prophylactic anticonvulsants in preventing seizures in 68 patients with supratentorial astrocytomas who had been treated with operation and irradiation and who had no previous history of convulsions. Thirty-three patients received prophylactic anticonvulsants and 38 patients did not. The incidence of all types of seizures (generalized convulsions or partial) was lower in patients receiving anticonvulsants. No seizures with an impairment of consciousness occurred in the patients with documented therapeutic anticonvulsant blood levels. The overall incidence of seizures was 39% in untreated patients and 21% in treated patients. The incidence of major seizures including tonic/clonic or partial complex seizures with impairment of consciousness was zero in patients with therapeutic anticonvulsant levels and 18% in untreated patients. Regarding the overall incidence of seizures in both groups, there tend to be fewer seizures in older patients, females, patients with a higher grade of malignancy, and patients who had a more radical resection of the tumor. This study suggests that seizures are a frequent occurrence after operation and irradiation for supratentorial glioma and that anticonvulsants may be effective in reducing the incidence of those seizures.

The role of an influx of macrophages and neovascularity in the resolution of vasogenic edema is not well defined. The inhibition of these processes with x-irradiation or parenteral corticosteroid administration was used to evaluate their contribution to the resolution of edema around a cortical freeze lesion in mice. The resorption of Evans blue, a marker of protein extravasation, was delayed in x-irradiated mice on the second day following a freeze lesion (p = 0.0075), which correlates with a delay in macrophage infiltration around the lesion. The specific gravity of the lesion and its border regions was significantly less in x-irradiated animals on day 7 than in controls (p = 0.00062), which correlates with a delay in new vessel formation around the lesion. Administration of corticosteroids from the time of production of the freeze lesion resulted in a specific gravity significantly less than control when measured eight days after the lesion (p = 0.01). Macrophages may participate by inhibiting the development of the macromolecular portion of vasogenic edema. The development of neovascularity correlates with the resorption of the aqueous portion of vasogenic edema. As with x-irradiation, corticosteroids administered from the time of freeze lesion inhibited the resorption of the aqueous portion of vasogenic edema, but they may suppress the spread of edema in this experimental model.

Adenosine receptors have been identified on brain cortical membranes and microvascular preparations. However, they have not been demonstrated on specific microvascular elements in isolation. 2-3H-chloroadenosine was used as a ligand to investigate the presence of adenosine receptors on isolated mouse cerebral smooth muscle membranes. The binding studies reveal the presence of a high affinity binding site with a Kd value of 33.3 nM and a maximal binding capacity (Bmax) of 283 fmol/mg protein. These findings demonstrate that there is an adenosine receptor on cerebral smooth muscle membranes.

Glial cells have been shown to influence several cerebral endothelial cell properties in vitro. A situation similar to the endothelial-astrocyte relationship existing at the blood-brain barrier (BBB) can be produced by growing cultured cerebral endothelium on one side of a filter and glial cells on the other in an enclosed double chamber. In this setting membrane-associated reaction product on the cerebral endothelial cell for both Na+,K+-ATPase and non-specific alkaline phosphatase was markedly increased when the endothelial cells were co-cultured with glial cells. In addition, the distribution of reaction product on the cerebral endothelial cell membrane was similar to that reported in vivo. These observations support a glial influence on enzyme activity at the BBB.

The treatment of trigeminal neuralgia by percutaneous retrogasserian glycerol rhizotomy was assessed in a series of 58 patients with a follow-up period ranging from 2 to 40 months postoperatively. All patients were considered medical failures prior to the procedure. Idiopathic trigeminal neuralgia was the diagnosis in 54 patients, and four patients had trigeminal neuralgia associated with multiple sclerosis. Forty-two patients (72%) reported complete relief from the procedure and are taking no medications. Four patients (7%) are much improved and require only minimal drug therapy. Twelve patients (21%) were considered treatment failures. The recurrence rate after initial relief of symptoms was 11%. Ten patients (17%) noticed a mild decrease in facial sensation following the procedure, and one additional patient had a profound sensory loss including loss of corneal reflex. The authors conclude that, while percutaneous retrogasserian glycerol rhizotomy may be useful in the treatment of trigeminal neuralgia, more clinical series and documentation of recurrence rate and complications are needed before any firm conclusions can be reached as to the efficacy of this therapy.

Speculation that meningiomas are subject to endocrine influence is supported by their higher incidence in women, reports of exacerbation of symptoms during pregnancy, and the discovery that these tumors harbor progesterone- and estrogen-binding proteins. To evaluate if these properties could be exploited therapeutically, specimens from three convexity meningiomas were used for estrogen- and progesterone-binding protein assays and establishment of tissue cultures. Each tumor (designated A, B, and C, respectively) was grown in experimental media containing 7.5 X 10(-5) to 10(-12) M 17 beta-estradiol, 2.5 X 10(-4) to 10(-12) M progesterone, 10(-7) to 10(-9) M tamoxifen (an estrogen antagonist), and 10(-6) to 10(-10) M RU486 (a progesterone antagonist). After incubation, cell growth was compared to control preparations by counting the meningioma cells present in each medium. Tumors A, B, and C contained estrogen-binding proteins of 8.45, 13.6, and 26.9 fmol/mg cytosol protein and progesterone-binding proteins of 210, 130, and 126 fmol/mg cytosol protein, respectively. The media containing 17 beta-estradiol and progesterone caused 21% to 36% growth stimulation in Tumors A and B. In Tumor A, the addition of tamoxifen stimulated growth by 35%, while it caused only transient stimulation in Tumor B and had no effect on Tumor C. RU486, the progesterone antagonist, caused inhibition of cell growth in all three tumors, ranging from 18% to 36%. These data suggest that selected meningiomas are subject to hormonal influence in vitro. The inhibition of meningioma growth in vitro by the antiprogesterone, RU486, has not been previously reported, and serves to encourage further development of alternative modes of therapy for recurrent and unresectable meningiomas.

The authors report a patient with an aneurysm of the carotid siphon who underwent ligation of the cervical carotid artery. Six years after this procedure, the patient suffered a subarachnoid hemorrhage from an apparent de novo aneurysm. Pertinent literature is reviewed to determine the incidence of this occurrence, and congenital arteriosclerotic and hemodynamic factors causing aneurysm enlargement are discussed.

Meningiomas have been shown to have steroid-binding proteins. In vitro, estradiol, progesterone, and the antiestrogen tamoxifen stimulate tumor growth. However, incubation of tumor cells with an antiprogesterone agent results in tumor inhibition. In this investigation, a human meningioma was implanted subcutaneously in athymic nude mice. Two treatment groups were established, one receiving the antiprogesterone agent RU-38486 (10 mg/kg/day in suspension) and the other receiving only vehicle. After 3 months, the tumor growth index (defined as the tumor volume at 3 months divided by the initial tumor volume) was 0.25 +/- 0.46 (mean +/- standard deviation) in the group receiving antiprogesterone and was 1.54 +/- 0.58 in the control group (p = 0.041). Further investigation of the effect of antiprogestational agents on the growth and hormone-binding proteins of other meningiomas will better define the mechanism of their effects.

Five patients who presented with clearly defined thoracic sensory levels were found by myelography and follow-up computed tomography (CT) to have cervical spinal cord compression. None of these patients had pain or an immediate preceding history of trauma. There is currently no satisfactory explanation for the large discrepancy between the sensory level and the level of cord compression in such patients. It is crucial that the clinician recognize the possibility of a cervical cord lesion in patients with such a presentation so that appropriate radiographic studies can be performed. Failure to appreciate this syndrome could result in failure to diagnose a treatable lesion.

The morphometric response of cerebral cortical arterioles to intracarotid hyperosmolar mannitol was assessed utilizing a technique of rapid freezing of rat brain tissue in vivo. A significant decrease in the wall to lumen (W/L) ratio was noted in the small parenchymal arterioles (20-49 mu) (p less than .0001) ipsilateral to the mannitol infusion. Larger arterioles showed a decreased W/L ratio but this change was not significant. Control infusion of 0.9% NaCl resulted in no change in arteriolar caliber. These results indicate that intracarotid hyperosmolar mannitol causes a direct vasodilatory response in small cerebral cortical arterioles.

A dose-escalation study of the calcium ion entry blocking drug nicardipine was performed using large dose infusions in 67 patients with recent aneurysmal subarachnoid hemorrhage (SAH). A safe, potentially therapeutic dose of the drug was determined. Patients admitted within 7 days of SAH from a documented cerebral aneurysm were entered into the study if no spasm was present on the initial angiogram. Nicardipine was administered as a continuous intravenous infusion throughout the 14-day period after SAH, regardless of the timing of surgery. To determine the safest possible dose, nicardipine was administered at seven dose levels from 0.01 to 0.15 mg/kg/hr. The total daily doses ranged from 27.7 mg to 375.0 mg. A follow-up angiogram was carried out on all 67 patients 7 to 10 days after SAH. Computerized tomography and neurological examinations were used to determine the presence of cerebral infarction. No major adverse effects, unexpected reactions, or permanent sequelae could be attributed to nicardipine. A decline in blood pressure was noted following administration of the drug. This occurred more frequently among patients given the largest dose but did not produce clinical problems or require discontinuation of the drug. Favorable outcomes were noted in 52 patients (78%). Vasospasm was found by arteriography in 31 patients (46%). A dose-related trend was noted: only eight (24%) of 33 patients treated at the highest dose level (approximately 10 mg/hr) developed arteriographic evidence of vasospasm. Symptomatic vasospasm was diagnosed in only two (6%) of 33 patients treated with this dose. Of the 34 patients receiving the lower dose levels, angiographic spasm was observed in 68% and symptomatic vasospasm in 27%. No deaths due to vasospasm occurred. Nicardipine appears to prevent both vasospasm and cerebral ischemia after SAH. A multicenter randomized double-blind trial to test this hypothesis is planned.

Adenosine uptake by cultured cerebral endothelium is a carrier-mediated process. The Km value for adenosine uptake is 5.0 microM and the vmax is 1.15 nmol/min/mg cell protein. The uptake system is inhibited by the adenosine analog 2-chloroadenosine at low adenosine concentrations. The results prove the existence of a nucleoside transport system associated with cerebral capillary endothelium.

Early angiography after cerebral arterial occlusion has been cited as potentially detrimental. This investigation evaluates the effect of acute angiographic contrast medium administration on the cortical edema induced by middle cerebral artery (MCA) occlusion. Sixteen rats underwent MCA occlusion, and after 1 hour half the rats underwent ipsilateral internal carotid injection of meglumine diatrizoate, whereas the remainder underwent cervical internal carotid exposure only. Six rats had only sham operations on the MCA and internal carotid, and 4 other rats served as normal controls. Cortical specific gravity was measured to reflect cerebral edema 4 hours after occlusion or sham operation. Specific gravity of the lateral frontal cortex in the hemisphere ipsilateral to occlusion was 1.0396 +/- 0.0011 (mean +/- SEM) when no angiographic contrast medium was administered, significantly less (p less than 0.01) than in rats exposed to contrast medium (specific gravity 1.0442 +/- 0.0005). The latter value was not significantly different from normal. Other cortical areas on the side of the contrast medium injection were also relatively dehydrated compared with normal controls. Early meglumine diatrizoate administration after MCA occlusion results in a decrease in cerebral cortical edema, possible by inducing an osmotic gradient that draws water from the extravascular space.

Tritiated glucose analogues 3-O-methylglucose (3-OMG) and 2-deoxyglucose (2-DG) were used to study glucose uptake properties in established lines of cultured mouse cerebral microvessel endothelium. Uptake of both analogues was similar in terms of rate and absolute amount for the first two minutes. Thereafter, intracellular accumulation of 2-DG continued at a more rapid rate because of intracellular phosphorylation of this substrate. The uptake of 3-OMG uptake was temperature-dependent, independent of Na+, and not inhibited by ouabain or 2,4-dinitrophenol. Phloretin and cytochalasin B both significantly inhibited 3-OMG uptake. Other hexoses in high concentration acted as competitive inhibitors at the endothelial cell membrane. Pre-incubation of cells with 50 mM D-glucose resulted in higher levels of 3-OMG accumulation than in control cells (counter-transport phenomenon). In contrast to findings at the blood-brain barrier in vivo, insulin was found to stimulate 3-OMG uptake. Maximal stimulation of approximately 3-fold was found at ambient insulin concentrations of 1,000 ng/ml or higher. The findings provide support at the cellular level for some components of the model of carrier-mediated glucose transport across the blood-brain barrier which has been postulated to exist in vivo. The effect of insulin is discussed in the light of new data that show stimulation of glucose analogue transport into isolated cerebral capillaries.