Acute Mesenteroaxial Volvulus in the Setting of Chronic Paraesophageal Hernia: A Case Report.

Hiatal hernia is a common finding in radiologic and gastroenterology evaluations. Here, we present a patient with an uncommon paraesophageal subtype who was managing her hiatal hernia symptoms conservatively and eventually developed the rare complication of mesenteroaxial gastric volvulus. The chronic history of this patient's hiatal hernia with classic complaints suggestive of gastric ischemia prompted clinical suspicion of volvulus. Here, we discuss the initial clinical presentation of this patient, imaging study, and emergent surgical intervention by robot-assisted laparoscopic gastric volvulus reduction, hiatal hernia repair, and Nissen fundoplication. Although the size and axis of rotation of this patient's volvulus made this case challenging, the prompt intervention prevented complications associated with volvulus and ischemia.

A single intra-PFC infusion of BDNF prevents cocaine-induced alterations in extracellular glutamate within the nucleus accumbens.

The glutamatergic pathway arising in the dorsomedial prefrontal cortex (dmPFC) and projecting to the nucleus accumbens (NAc) core is a critical component of the reward circuitry that underlies reinstatement to cocaine-seeking behavior. Brain-derived neurotrophic factor (BDNF) is expressed by and modulates PFC-NAc neurons. BDNF infusion into the dmPFC attenuates reinstatement to cocaine-seeking behavior, as well as some cocaine-induced molecular adaptations within the NAc. In the present study, it is demonstrated that a single intra-dmPFC infusion of BDNF prevents cocaine self-administration-induced reduction in basal extracellular glutamate, as well as cocaine prime-induced increases in extracellular glutamate levels within the NAc. These data suggest that intra-PFC BDNF attenuates reinstatement to cocaine-seeking behavior by normalizing cocaine-induced neuroadaptations that alter glutamate neurotransmission within the NAc.

Brain-derived neurotrophic factor and cocaine addiction.

The effects of brain-derived neurotrophic factor (BDNF) on cocaine-seeking are brain region-specific. Infusion of BDNF into subcortical structures, like the nucleus accumbens and ventral tegmental area, enhances cocaine-induced behavioral sensitization and cocaine-seeking. Conversely, repeated administration of BDNF antiserum into the nucleus accumbens during chronic cocaine self-administration attenuates cocaine-induced reinstatement. In contrast, BDNF infusion into the dorsomedial prefrontal cortex immediately following a final session of cocaine self-administration attenuates relapse to cocaine-seeking after abstinence, as well as cue- and cocaine prime-induced reinstatement of cocaine-seeking following extinction. BDNF-induced alterations in the ERK-MAP kinase cascade and in prefronto-accumbens glutamatergic transmission are implicated in BDNF's ability to alter cocaine-seeking. Within 22 hours after infusion into the prefrontal cortex, BDNF increases BDNF protein in prefrontal cortical targets, including nucleus accumbens, and restores cocaine-mediated decreases in phospho-ERK expression in the nucleus accumbens. Furthermore, 3 weeks after BDNF infusion in animals with a cocaine self-administration history, suppressed basal levels of glutamate are normalized and a cocaine prime-induced increase in extracellular glutamate levels in the nucleus accumbens is prevented. Thus, BDNF may have local effects at the site of infusion and distal effects in target areas that are critical to mediating or preventing cocaine-induced dysfunctional neuroadaptations.

A BDNF infusion into the medial prefrontal cortex suppresses cocaine seeking in rats.

The medial prefrontal cortex (mPFC) is critical for reinstatement of cocaine seeking and is the main source of brain-derived neurotrophic factor (BDNF) to striatal regions of the brain relapse circuitry. To test the hypothesis that BDNF in the mPFC regulates cocaine-seeking behavior, rats were trained to press a lever for cocaine infusions (0.2 mg/inf, 2 h/day) paired with light+tone conditioned stimulus (CS) presentations on 10 consecutive days. After the last self-administration session, rats received a single infusion of BDNF (0.75 microg/0.5 microL/side) into the mPFC; this manipulation produced protracted effects on cocaine-seeking behavior (non-reinforced lever pressing). BDNF pretreatment administered after the last session attenuated cocaine seeking 22 h later and, remarkably, it also blocked cocaine-induced suppression of phospho-extracellular-regulated kinase and elevated BDNF immunoreactivity in the nucleus accumbens. The same pretreatment also suppressed cocaine-seeking behavior elicited by response-contingent CS presentations after 6 days of forced abstinence or extinction training, as well as a cocaine challenge injection (10 mg/kg, i.p.) after extinction training. However, BDNF infused into the mPFC had no effect on food-seeking behavior. Furthermore, BDNF infused on the sixth day of abstinence failed to alter responding, suggesting that the regulatory influence of BDNF is time limited. The suppressive effects of BDNF infused into the mPFC on cocaine seeking indicate that BDNF regulates cortical pathways implicated in relapse to drug seeking and that corticostriatal BDNF adaptations during early abstinence diminish compulsive drug seeking.

Convergent evidence from microdialysis and presynaptic immunolabeling for the regulation of gamma-aminobutyric acid release in the globus pallidus following acute clozapine or haloperidol administration in rats.

Antipsychotic drugs (APDs) have been primarily characterized for their effects on dopaminergic terminal regions in the brain, especially within the corpus striatum. Efferent GABA pathways are the primary outflow of striatal processing via their projections to the substantia nigra and the globus pallidus (GP). In the current study, we analyzed changes in pallidal GABA function following acute APD administration by means of in vivo microdialysis, followed by immunolabeling of presynaptic GABA terminal density in the contralateral hemisphere of the same animals. Acute administration of the atypical APD, clozapine (10 or 30 mg/kg, s.c.), produced a dose-dependent decrease in extracellular GABA. A corresponding dose-dependent increase in the density of presynaptic terminal GABA immunolabeling in the GP was found. In contrast, the typical APD, haloperidol (1 or 3 mg/kg, s.c.), had no significant effects on either measure, although a non-significant increase in extracellular GABA and decrease in the density of GABA terminal immunolabeling was noted. Paw retraction tests conducted during the time of microdialysis showed that haloperidol produced a typical pattern of highly pronounced motor impairment, while clozapine showed an atypical profile of minimal catalepsy. These complementary results obtained from in vivo neurochemistry and presynaptic neurotransmitter labeling suggest that systemic clozapine suppresses neuronal GABA release within the GP. This decrease in released pallidal GABA may play a role in the low motor side-effect liability of atypical APDs.