Chemical sympathectomy increases susceptibility to ocular herpes simplex virus type 1 infection

The cornea is one of the most highly innervated tissues in the mammalian host. We hypothesized changes to cornea innervation through chemical sympathectomy would significantly alter the host response to the neurotropic viral pathogen, herpes simplex virus type 1 (HSV-1) following ocular infection. Mice treated with 6-hydroxydopamine hydrobromide displayed reduced tyrosine hydroxylase-positive fibers residing in the cornea. Sympathectomized mice were also found to show a transient rise in virus recovered in infected tissues and succumbed to infection in greater numbers. Whereas there were no differences in infiltrating leukocyte populations including HSV-1-specific cytotoxic T lymphocytes in the infected tissue, an increase in substance P and a decrease in IFN-gamma levels in the trigeminal ganglion but not brain stem of sympathectomized mice were noted. Sympathectomized mice treated with the neurokinin-1 receptor antagonist L703,606 had delayed mortality implicating the involvement of substance P in HSV-1-mediated death.     

Effects of D-cycloserine on the behavior and ERK activity in the amygdala: role of individual anxiety levels

Low dose of D-cycloserine (DCS), a partial agonist of glycine binding site on N-methyl-D-aspartate (NMDA) receptors, can facilitate extracellular signal-regulated kinase1/2 (ERK1/2) activity in the amygdala and modulate emotional behavior. However, the relationship between ERK1/2 activation, individual anxiety levels, and DCS is unknown. Therefore, based on open arm time in the elevated plus-maze, male Wistar rats were divided into subgroups with either low (LOA) or high open arm (HOA) time. Open arm time is usually accepted as a critical index of unconditioned anxiety-like/avoidance behavior. On the following day, DCS (30 mg/kg, i.p.) was administered 30 min before the second elevated plus-maze test. On day 8 and 9, the rats were subjected to a 2-day session of the forced swim test, receiving the DCS treatment again 30 min before the 2nd day. On the 16th day, 30 min after the administration of DCS, the rats were sacrificed in order to detect the phosphorylation of ERK1/2 (p-ERK1/2) in the amygdala by Western blots. The results showed that: (1) DCS decreased the open arm time in HOA but not LOA rats. (2) DCS suppressed the immobility in the day-2 trial of the forced swim test and increased the p-ERK1/2 level in the amygdala in LOA but not HOA rats. This is the first instance data has been found indicating different sensitivities of p-ERK1/2 and behavioral responses to the treatment of DCS between HOA and LOA rats. The results suggest that the activity of NMDA receptor-mediated ERK1/2 signaling is mediated by individual behavioral differences which are related to the antidepressant-like activity of DCS. This study provides first insight into the pathophysiological role of ERK signaling with regard to individual differences in emotional behavior.     

Three-dimensional constructive interference in steady-state magnetic resonance imaging in syringomyelia: advantages over conventional imaging

OBJECT: Neuroradiology has become indispensable in detecting the pathophysiology in syringomyelia. Constructive interference in steady-state (CISS) magnetic resonance (MR) imaging can provide superior contrast at the sub-arachnoid tissue borders. As this region is critical in preoperative evaluation, the authors hypothesized that CISS imaging would provide superior assessment of syrinx pathology and surgical planning. METHODS: Based on records collected from a database of 130 patients with syringomyelia treated at the authors' institution, 59 patients were prospectively evaluated with complete neuroradiological examinations. In addition to routine acquisitions with FLAIR, T1- and T2-weighted, and contrast-enhanced MR imaging series, the authors obtained sagittal cardiac-gated sequences to visualize cerebrospinal fluid (CSF) pulsations and axial 3D CISS MR sequences to detect focal arachnoid webs. Statistical qualitative and quantitative evaluations of spinal cord/CSF contrast, spinal cord/CSF delineation, motion artifacts, and artifacts induced by pulsatile CSF flow were performed. RESULTS: The 3D CISS MR sequences demonstrated a contrast-to-noise ratio significantly better than any other routine imaging sequence (p < 0.001). Moreover, 3D CISS imaging can detect more subarachnoid webs and cavitations in the syrinx than T2-weighted MR imaging with less flow-void artifact. The limitation of 3D CISS imaging is a susceptibility to motion artifacts that can cause reduced spatial resolution. Lengthy acquisition times for axial segments can be reduced with multiplanar reconstruction of 3D CISS-generated sagittal images. CONCLUSIONS: Constructive interference in steady-state imaging is the MR sequence of choice in the preoperative evaluation of syringomyelia, allowing significantly higher detection rates of focal subarachnoid webs, whereas standard T2-weighted MR imaging shows turbulent CSF flow voids. Constructive interference in steady-state MR imaging enables the neurosurgeon to accurately identify cases requiring decompression for obstructed CSF. Motion artifacts can be eliminated with technical variations.     

Task-irrelevant visual letters interact with the processing of speech sounds in heteromodal and unimodal cortex

Letters and speech sounds are the basic units of correspondence between spoken and written language. Associating auditory information of speech sounds with visual information of letters is critical for learning to read; however, the neural mechanisms underlying this association remain poorly understood. The present functional magnetic resonance imaging study investigates the automaticity and behavioral relevance of integrating letters and speech sounds. Within a unimodal auditory identification task, speech sounds were presented in isolation (unimodally) or bimodally in congruent and incongruent combinations with visual letters. Furthermore, the quality of the visual letters was manipulated parametrically. Our analyses revealed that the presentation of congruent visual letters led to a behavioral improvement in identifying speech sounds, which was paralleled by a similar modulation of cortical responses in the left superior temporal sulcus. Under low visual noise, cortical responses in superior temporal and occipito-temporal cortex were further modulated by the congruency between auditory and visual stimuli. These cross-modal modulations of performance and cortical responses during an unimodal auditory task (speech identification) indicate the existence of a strong and automatic functional coupling between processing of letters (orthography) and speech (phonology) in the literate adult brain.     

Stable trichimerism after marrow grafting from 2 DLA-identical canine donors and nonmyeloablative conditioning

Although hematopoietic cell transplantation (HCT) is generally accomplished using a single donor, multiple donors have been used to enhance the speed of engraftment, particularly in the case of umbilical cord blood grafts. Here we posed the question in the canine HCT model whether stable dual-donor chimerism could be established using 2 DLA-identical donors. We identified 8 DLA-identical littermate triplets in which the marrow recipients received 2 Gy total body irradiation followed by marrow infusions from 2 donors and postgrafting immunosuppression. All 8 dogs showed initial "trichimerism," which was sustained in 5 dogs, while 2 dogs rejected one of the allografts and remained mixed chimeras, and 1 dog rejected both allografts. Immune function in one trichimeric dog, as tested by mixed leukocyte culture response and antibody response to sheep red blood cells, was found to be normal. Five dogs received kidney grafts from one of their respective marrow donors at least 6 months after HCT without immunosuppressive drugs, and grafts in 4 dogs are surviving without rejection. In summary, following nonmyeloablative conditioning, simultaneous administration of marrow grafts from 2 DLA-identical littermates could result in sustained trichimerism, and immunologic tolerance could include a kidney graft from one of the marrow donors.     

Surgical animal models of heart failure related to coronary heart disease

Coronary heart disease is caused by atherosclerotic narrowing of coronary arteries. It accounts for about two-thirds of heart failure cases, which are frequently secondary to myocardial infarction. Despite considerable progress in the understanding and management of heart failure, its incidence, prevalence and economic burden are steadily increasing. Therefore, efficient preventive and therapeutic measures are urgently needed. In order to investigate the mechanisms involved in the pathogenesis of coronary heart disease-related heart failure and to develop therapies, appropriate animal models are indispensable. According to the aetiology of this disorder, surgical models are based on various methods allowing for the narrowing or occlusion of coronary arteries. Depending on the duration and extent of the impairment of coronary blood flow and its consequences for cardiac tissue, these are classified as models of myocardial infarction, cardiac ischemia/reperfusion injury, or chronic cardiac ischemia. In addition, factors such as species, strain, and gender of the laboratory animals also significantly contribute to the pathophysiology of the induced disorder and, therefore, have to be taken into consideration thoroughly when an animal model is to be established.