Association between Early Ischemic Changes and Collaterals in Acute Stroke: A Retrospective Study.

BACKGROUND AND PURPOSE: The quality of leptomeningeal collaterals may influence the speed of infarct progression in acute stroke. Our main objective was to evaluate the association of leptomeningeal collateral score and its interaction with time with ischemic changes on CT in patients with acute stroke. MATERIALS AND METHODS: Adult patients with acute stroke symptoms and anterior circulation large-vessel occlusion on CTA from 2015 to 2019 were included. Routinely performed NCCT and multiphase CTA were reviewed to assess ASPECTS and the leptomeningeal collateral score. We built multivariate regression models to assess the association between leptomeningeal collateral score and its interaction with time and ASPECTS. Performance measures to predict poor ASPECTS at different time thresholds (identified with receiver operating characteristic curve analysis) were estimated in a subgroup of patients with poor leptomeningeal collateral scores. RESULTS: Leptomeningeal collateral scores 0-1 were associated with lower ASPECTS, and the model with dichotomized and trichotomized leptomeningeal collateral score showed a significant multiplicative interaction between time and the leptomeningeal collateral score. The negative predictive value for poor ASPECTS was >0.9 for at least the first 3 hours from stroke onset to imaging, and the positive predictive value was <0.5 for every time threshold tested in the subgroup of patients with leptomeningeal collateral scores 0-3. CONCLUSIONS: Poor (0-1) leptomeningeal collateral scores were associated with lower ASPECTS, and an increase in time has a multiplicative interaction with the leptomeningeal collateral score on ASPECTS.

Arteriovenous malformation of the mandible: embolization and direct injection therapy.

Arteriovenous malformation (AVM) of the mandible is a rare entity but one that can be potentially fatal as a result of massive hemorrhage. Traditional treatment involved extensive surgical resection of the mandible. With the advent of improved endovascular techniques, interventional radiology is now the best method to control active hemorrhage and ultimately cure these lesions. The authors describe three cases of successfully treated mandibular AVM by percutaneous and/or endovascular techniques.

Maternal prenatal, postpartum, and concurrent stressors and temperament in 3-year-olds: a person and variable analysis.

The study was based on the assumption that stressors in the lives of pregnant and parenting women are processes that affect prenatal, postpartum, and concurrent maternal hormones and emotions and that these processes affect child temperament. The hypotheses were tested in a group of 67 young mothers and their 3-year-old children. Mothers were clustered into groups based on longitudinal patterns of hormones and emotions at prenatal, postpartum. and 3-year follow-up assessments. The analyses focused on relating maternal patterns of hormones and emotions to the child's temperament at age 3 years. Temperament was assessed by questionnaire and observation of behavior during a challenging situation. Illustrative findings included the following. Verbal aggression and nonverbal aggression were significantly higher in children of mothers in the low prenatal hormone cluster than children of mothers in the high prenatal hormone cluster. Children of mothers in the postpartum low testosterone (T), estradiol (E2), and androstenedione (delta4-A) and medium cortisol (Cort) cluster (mainly low hormone cluster) exhibited significantly more physical aggression than children of mothers in the medium T and A4-A, high E2 and low Cort cluster. Maternal patterns of hormones, emotions, and parenting attitudes and practices were related to multiple aspects of temperament when the children were age 3 years. The findings support the important role of maternal biological and psychological processes in the development of child temperament.

Differences in NK cell function in mice bred for high and low aggression: genetic linkage between complex behavioral and immunological traits?

In previous studies, we found differences in cellular immune responsiveness in Institute for Cancer Research (ICR) mice selectively bred for high and low levels of aggression. Compared to the high aggressive line, the low aggressive line had low levels of natural killer (NK) and T cell activity and increased susceptibility to tumor development. To dissect further this novel association, experiments were designed to test two competing hypotheses. The first hypothesis was that the phenotypic expression of the line differences in NK cell activity are dependent on and regulated by the expression of high and low levels aggressive behavior in the lines. The alternative hypothesis was that the differences in immune status are independent of the expression of aggression by the lines, suggesting linkage between a subset of genes involved in determining these complex behavioral and immunological traits or pleiotropic gene effects on both traits. In Experiment 1, three conditions of postweaning social experience (mice singly housed, group housed within line, or group housed between lines) were tested in males to determine whether experiential conditions which modify the expression of aggression would in turn modify the line differences in NK cell activity. This experiment revealed that the difference in NK cell activity between high aggressive and low aggressive male mice was attributable to line only. The different postweaning social conditions examined had no effect on modifying the differences in NK activity, and social dominance hierarchy did not correlate with levels of NK cell activity. Whereas males of the high and low lines exhibit differences in aggressive behaviors across most contexts, females do not exhibit such differences except in response to an intruder during the postpartum period. Therefore, in Experiment 2 we compared the NK cell activity of nulliparous females of the high and low aggressive lines. Under these conditions, females of the low aggressive line had low levels of NK activity compared to high aggressive females (differences comparable to those seen between males of the high and low lines). Taken together, these experiments lend support to the hypothesis that this association may be due to a genetic linkage between subsets of genes involved in determining these complex behavioral and immunological traits, or may possibly represent a fortuitous association which occurred during the selective breeding.

D1 dopamine receptors and the reversal of isolation-induced behaviors in mice.

In a previous study, it was demonstrated that the high rates of social reactivity exhibited by isolated male mice in a dyadic encounter were mediated, at least in part, by an increased sensitivity of the D1 dopamine receptors. The present research was guided by the hypothesis that the behavioral effects of isolation are reversible, and that changes in dopaminergic function support this reversibility. To this end, mice selectively bred for high and low levels of aggression were reared in isolation from weaning (21 days) to puberty (45 days), at which point they were either assigned to groups or left in isolation until day 69. By comparison to the continuous isolation condition, mice that eventually formed groups exhibited significantly less reactivity in a dyadic test conducted on day 69, showed a reduced response to dihydrexidine (DHX), and a decreased density of D1 dopamine receptors. This experiment provided evidence for the plasticity of the neurobiological system supporting reactive responses, and confirmed the view that its functional organization is open to experientially-induced changes.

D2-like dopamine receptor mediation of social-emotional reactivity in a mouse model of anxiety: strain and experience effects.

We examined the effects of the D2-like dopamine receptor agonist quinpirole on social-emotional reactivity in two inbred mouse strains. An important objective of this study was to determine whether these effects could be modulated by differential housing conditions (i.e., isolation versus group housing). Moreover, as motor activity is an important control for the assessment of drug effects on emotional behavior, the effects of quinpirole were tested in two inbred mouse strains (A/J and C57BL/6J) low and high in motor activity, respectively. Levels of emotional reactivity were assessed in response to mild social stimulation provided by a nonaggressive conspecific. Quinpirole increased stationary forms of reactivity (i.e., startle, kicking, defensive posture, vocalization) in both isolated and group-housed A/J mice. This effect was more pronounced and observed at lower doses in isolated than in group-housed A/J mice. Quinpirole also induced jump behavior in isolated but not group-housed A/J mice. The shift to the left in the dose-response curve of quinpirole in isolated A/J mice indicated that D2-like dopamine receptor functions can be altered by social experience. Quinpirole only marginally increased stationary and locomotor reactivity (i.e., jump) in isolated C57BL/6J mice, whereas it markedly reduced motor activity in group-housed mice of this strain. The investigation of emotional reactivity within a social context and using strains that differ in motor activity permitted the effects of drugs on emotional reactivity to be dissociated from the effects on motor activity. Given that social-emotional reactivity was elicited by what typically should have been mild and nonthreatening stimuli, this model may be highly relevant to understanding the neurobiology of anxiety. Finally, these data support an important role for dopamine in the mediation of social-emotional reactivity.

D1 dopamine receptor mediation of social and nonsocial emotional reactivity in mice: effects of housing and strain difference in motor activity.

The study examined the effects of isolation housing and the role of D1 dopamine receptors on isolation-induced social and nonsocial (acoustic startle) reactivity in mice high (C57BL/6) and low (A) in motor activity. Isolation housing had no effect on acoustic startle but increased strain-specific forms of social reactivity. The D1 agonist dihydrexidine (DHX) increased acoustic startle in isolated mice of both strains, but this effect was more pronounced in C57BL/6 mice. In this strain, DHX and the D1 agonist SKF-81297 increased locomotor forms of social reactivity (e.g., escape, jump), whereas the D1 antagonist SCH-23390 increased stationary reactivity (e.g., freezing). In A mice, DHX and SKF-81297 increased and decreased stationary reactivity, respectively, whereas SCH-23390 had no effect on these behaviors. Administration of SKF-81297 after pretreatment with SCH-23390 or the D2 antagonist sulpiride confirmed the importance of D1 receptors in mediating specific forms of social reactivity in C57BL/6 mice. These results suggest an important relationship between social reactivity and motor activity and an important, albeit strain-dependent, role for D1 receptors in mediating specific emotional behaviors.

Effects of the putative dopamine D3 receptor antagonist PNU 99194A on motor behavior and emotional reactivity in C57BL/6J mice.

Due to the regional expression of D3 dopamine receptors in limbic areas of the brain, there has been considerable interest in the potential role of this receptor subtype in mediating emotional behavior. Previous studies in habituated rats have shown that the putative dopamine D3 receptor antagonist 5,6-dimethoxy-2-(di-n-propylamino)indan (PNU 99194A) increased locomotor behavior. The present study examined the effects PNU 99194A on motor and emotional behaviors in C57BL/6J mice. Motor behavior was assessed in both habituated and nonhabituated mice. Emotional behavior was assessed using the elevated plus-maze and a social context involving an isolated C57BL/6J mouse and a nonaggressive conspecific. In mice habituated to the activity chamber prior to drug administration, PNU 99194A increased locomotion and rearing at lower doses (5, 10 mg/kg) whereas higher doses (20, 30 mg/kg) reduced these behaviors early in the test session. Thigmotaxis was increased independently of the effects on motor behavior. In mice exposed to the activity chamber for the first time, PNU 99194A produced a weak motor activation at lower doses and an initial decrease in motor behavior at higher doses that was followed by an increase in locomotion later in the test session. PNU 99194A had no systematic effects on activity in the elevated plus-maze, but dose-dependently increased flight reactivity in the social reactivity paradigm. These and previous findings raise questions about the role of dopamine D3 receptors in mediating motor behavior and emotional reactivity as well as the pharmacology of this putative dopamine D3 receptor antagonist.

Rearing conditions alter social reactivity and D1 dopamine receptors in high- and low-aggressive mice.

As a result of selective breeding, NC900 mice exhibit isolation-induced attacks in a social interaction test, whereas NC100 mice do not attack but freeze instead. Administration of the D1 receptor agonist dihydrexidine was previously shown to reduce aggression in NC900 mice and nonagonistic approaches in NC100 mice. This resulted from induction of a marked social reactivity in both selected lines. Because isolation rearing also induces social reactivity, the present experiment was designed to test the hypothesis that D1 dopamine receptors mediate isolation-induced social reactivity. Isolation was expected to potentiate the effects of a D1 agonist and to increase D1 dopamine receptor density. Thus, isolated and group-reared mice were administered dihydrexidine, and their social behavior was compared to vehicle-injected controls. Dihydrexidine induced higher levels of reactivity among isolated than among group-reared animals, especially in NC900 mice. In independent experiments, increased densities of D1 dopamine receptors in the striatum of isolated animals were found, with no change in affinity. These studies suggest an important role for the D1 dopamine receptor as a mediator of isolation-induced social reactivity.

Cystic lymphangioma of the colon: ultrasonographic and computed tomographic features.

Cystic lymphangioma is a rare benign tumour of the gastrointestinal tract. The authors describe a 52-year-old woman with cystic lymphangioma in the ascending colon. Ultrasonographically, the lesion was compressible and anechoic and showed posterior acoustic enhancement. Doppler analysis showed no flow within the lesion. On computed tomography the lesion appeared as a focal thickening of the colonic wall with attenuation values of 6 to 10 Hounsfield units. The lesion extended along the wall and did not invade the adjacent fat. It could not be located during endoscopy or laparotomy and was eventually located for resection with intraoperative ultrasonography.

Association of genetic differences in social behavior and cellular immune responsiveness: effects of social experience.

We have recently demonstrated that selective breeding of ICR mice for differences in social behavior (i.e., high versus low levels of social isolation-induced aggression) are related to increased susceptibility to tumor development and reduced levels of natural killer (NK) cell activity. In the present investigation, we sought to extend examination of the line differences in immune status to T and B cell responsiveness. In addition, we also sought to determine if social experience contributes to line differences in immune responsiveness. A cosibial design was used to examine whether single vs group housing modified the magnitude of line differences in immune status. Compared to aggressive (NC900) mice, nonaggressive (NC100) mice had significantly lower T cell proliferative responses to concanavalin A, lower IL-2 and gamma-interferon production, as well as significantly lower NK activity. Of the various measures of cellular immune responsiveness, housing condition was found to have a significant effect only on NK activity. No significant line by housing interactions were found for any of the immune measures tested. The present data demonstrate that the genetic selection for differences in social behavior is associated with line differences in several parameters of cellular immune responsiveness. These mouse lines provide a valuable research model to examine the association between selection for genetic differences in social behavior and differences in immune responsiveness.

Social reactivity and D1 dopamine receptors: studies in mice selectively bred for high and low levels of aggression.

Robust individual differences in social behavior have been obtained by selectively breeding Institute for Cancer Research mice for high and low levels of aggression. As previously shown, when paired with a non-selected group-housed partner mouse, NC900 mice exhibit isolation-induced aggression. Conversely, NC100 mice fail to attack, freezing upon social contact. Previous studies have established that NC100 mice have lower dopamine concentrations in nucleus accumbens and caudate nucleus, with increased dopamine receptor densities in these same regions. Thus, we wished to determine the effect of administration of a dopamine receptor agonist on social behavior. Mice of both lines were administered 0, 1, 3, or 10 mg/kg (SC) of the full efficacy D1 receptor agonist dihydrexidine, and their behavior was assessed in a social interaction test. Dihydrexidine reduced aggression in NC900 mice and nonagonistic approach in NC100 mice in a dose dependent manner. In both cases, this resulted from induction of a marked reactivity to mild social stimulation as measured by increases in behaviors such as escape, reflexive kicking, and vocalizations. Dihydrexidine had no systematic effect on the freezing behavior characteristic of the low-aggressive line. In independent experiments, mice were pretreated with either the D1 antagonist SCH-23390 (.1 mg/kg) or the selective D2 antagonist remoxipride (1.0 mg/kg), after which they received dihydrexidine (10 mg/kg) and were tested as above. The effects of dihydrexidine on social reactivity in mice of both lines were significantly antagonized by SCH-23390 but not attenuated by remoxipride.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic differences in social behavior: relation to natural killer cell function and susceptibility to tumor development.

The hypothesis that certain heritable personality traits would correlate with increased vulnerability to tumor development and reduced natural killer (NK) cell function was tested in mice selectively bred for high and low levels of aggression. This selection program produces a line of mice that fail to exhibit species typical, isolation-induced aggression, but appear socially inhibited in response to a novel partner mouse. All socially inhibited mice developed 3-methylcholanthrene-induced tumors compared with only 44% of the aggressive mice. Basal NK activity was also significantly lower among socially inhibited mice. Conversely, there were no line differences in NK activity between the aggressive line and nonselected, socially isolated mice, consistent with other unidirectional outcomes of this selective breeding program. No significant line differences were present for nonsocial measures of emotional reactivity (e.g., fearfulness) or serum corticosterone levels. These findings support the hypothesis that social "traits" may be related to immune function and tumor susceptibility.

Development, microevolution, and social behavior.

The central questions of social development--from the roots of mother-infant attachment to the plasticity of aggressive behavior--pivot on the relations between genetic and ontogenetic sources of variance. It is proposed that (a) developmental, experiential, and microevolutionary processes typically collaborate, rather than compete, in achieving social adaptation; (b) social behavior patterns are mostly closed to modification in the course of development and across generations, but avenues of vulnerability exist in ontogeny and microevolution for dynamic, rapid, and reversible changes in key features; (c) a general avenue for change is delay or acceleration in the developmental onset of one or more features of the behavior pattern, which in turn modifies the functions and properties of the adaptive configuration; and (d) the features of social behavior that are open to rapid change in ontogeny should be open as well to rapid changes in microevolution, although different underlying processes may be involved. Empirical findings from the investigation of aggressive interactions are used to illustrate this proposal on the dual genesis and coincident adaptation of social behaviors.

A developmental-genetic analysis of aggressive behavior in mice (Mus musculus): III. Behavioral mediation by heightened reactivity or immobility?

This research was designed to investigate development and behavioral mediation in lines of ICR mice that have been selectively bred for aggressive behavior. General behavioral reactivity and behavioral immobility have been implicated as potential mediators by prior analyses of preattack interactions. To evaluate the separate roles of these dispositions, the emergence of attacks in genetically selected lines was tracked for 11 years by three levels of analysis: over successive generations, over development, and over dyadic interactions. Convergent outcomes were observed in all three levels with respect to two findings: (a) Robust line differences were obtained in attack behaviors, and (b) strong associations were found between line differences in attacks and line differences in behavioral immobility. Conversely, all three levels of analysis indicated a weak and inconsistent association between line differences in attacks and measures of social and nonsocial reactivity.