Blast exposure causes dynamic microglial/macrophage responses and microdomains of brain microvessel dysfunction.

Exposure to blast overpressure (BOP) is associated with behavioral, cognitive, and neuroimaging abnormalities. We investigated the dynamic responses of cortical vasculature and its relation to microglia/macrophage activation in mice using intravital two-photon microscopy following mild blast exposure. We found that blast caused vascular dysfunction evidenced by microdomains of aberrant vascular permeability. Microglial/macrophage activation was specifically associated with these restricted microdomains, as evidenced by rapid microglial process retraction, increased ameboid morphology, and escape of blood-borne Q-dot tracers that were internalized in microglial/macrophage cell bodies and phagosome-like compartments. Microdomains of cortical vascular disruption and microglial/macrophage activation were also associated with aberrant tight junction morphology that was more prominent after repetitive (3×) blast exposure. Repetitive, but not single, BOPs also caused TNFα elevation two weeks post-blast. In addition, following a single BOP we found that aberrantly phosphorylated tau rapidly accumulated in perivascular domains, but cleared within four hours, suggesting it was removed from the perivascular area, degraded, and/or dephosphorylated. Taken together these findings argue that mild blast exposure causes an evolving CNS insult that is initiated by discrete disturbances of vascular function, thereby setting the stage for more protracted and more widespread neuroinflammatory responses.

Organization of corticostriatal projections from the vibrissal representations in the primary motor and somatosensory cortical areas of rodents.

To characterize corticostriatal projections from rodent sensorimotor cortex, the anterograde tracers biotinylated dextran amine (BDA) and fluororuby (FR) were injected into the whisker representations of the primary motor (MI) and somatosensory (SI) cortices. Reconstructions of labeled terminals and their beaded varicosities in the neostriatum and thalamus were analyzed quantitatively to determine the degree of labeled overlap in both of these subcortical structures. Corticostriatal projections from the vibrissal representation in MI were more extensive than corresponding projections from SI. Both cortical areas sent dense projections to the dorsolateral neostriatum, but the MI vibrissal representation also projected to regions located more rostrally and medially. Despite these differences, both MI and SI projected to overlapping parts of the dorsolateral neostriatum. Tracer injections in both cortical areas also produced dense anterograde and retrograde labeling in the medial sector of the posterior complex of the thalamus (POm). Because POm is somatotopically organized and has reciprocal connections with both SI and MI cortices, the amount of labeled overlap in POm was used to indicate whether the tracers were injected into corresponding whisker representations of MI and SI. We found that the proportion of labeled overlap in the neostriatum was highly correlated with the amount of labeled overlap in POm. These results indicate that the rodent neostriatum receives convergent projections from corresponding regions in MI and SI cortex. Furthermore, the thalamocortical projections of the POm indicate that it may modulate corticostriatal outputs from corresponding representations in MI and SI.

Overlapping corticostriatal projections from the rodent vibrissal representations in primary and secondary somatosensory cortex.

To determine whether the neostriatum receives overlapping projections from two somatosensory cortical areas, the anterograde tracers biotinylated dextran amine (BDA) and fluoro-ruby (FR) were injected into the whisker representations of primary (SI) and secondary (SII) somatosensory cortex. Reconstructions of labeled terminals and their beaded varicosities in the neostriatum and thalamus were analyzed quantitatively to compare the extent of overlapping projections to both subcortical structures. Corticostriatal projections from focal sites in both somatosensory areas exhibited substantial amounts of divergence within the dorsolateral neostriatum. Most of the labeled terminals were concentrated in densely packed arborizations that occupied lamellar-shaped regions along the dorsolateral edge of the neostriatum. Tracer injections in both cortical areas also produced dense anterograde and retrograde labeling in the thalamus, especially in the ventrobasal complex (VB) and in the medial part of the posterior (POm) nucleus. Because these thalamic regions are topographically organized and have reciprocal connections with corresponding representations in both SI and SII, the amount of labeled overlap in the thalamus was used to indicate the degree of somatotopic correspondence at the SI and SII injection sites. We found that the proportion of overlapping projections to the neostriatum was moderately correlated with the amount of overlap observed in the thalamus. This result strongly indicates that specific sites in the dorsolateral neostriatum receive convergent projections from corresponding somatotopic representations in SI and SII, but also suggests that some of the corticostriatal divergence may reflect neostriatal integration of somatosensory information from noncorresponding representations in SI and SII.

Overlapping corticostriatal projections from the rodent vibrissal representations in primary and secondary somatosensory cortex.

To determine whether the neostriatum receives overlapping projections from two somatosensory cortical areas, the anterograde tracers biotinylated dextran amine (BDA) and fluoro-ruby (FR) were injected into the whisker representations of primary (SI) and secondary (SII) somatosensory cortex. Reconstructions of labeled terminals and their beaded varicosities in the neostriatum and thalamus were analyzed quantitatively to compare the extent of overlapping projections to both subcortical structures. Corticostriatal projections from focal sites in both somatosensory areas exhibited substantial amounts of divergence within the dorsolateral neostriatum. Most of the labeled terminals were concentrated in densely packed arborizations that occupied lamellar-shaped regions along the dorsolateral edge of the neostriatum. Tracer injections in both cortical areas also produced dense anterograde and retrograde labeling in the thalamus, especially in the ventrobasal complex (VB) and in the medial part of the posterior (POm) nucleus. Because these thalamic regions are topographically organized and have reciprocal connections with corresponding representations in both SI and SII, the amount of labeled overlap in the thalamus was used to indicate the degree of somatotopic correspondence at the SI and SII injection sites. We found that the proportion of overlapping projections to the neostriatum was moderately correlated with the amount of overlap observed in the thalamus. This result strongly indicates that specific sites in the dorsolateral neostriatum receive convergent projections from corresponding somatotopic representations in SI and SII, but also suggests that some of the corticostriatal divergence may reflect neostriatal integration of somatosensory information from noncorresponding representations in SI and SII.

A comparative biomechanical investigation of anterior lumbar interbody cages: central and bilateral approaches.

BACKGROUND: Some biomechanical studies have been performed to evaluate the stabilization provided by interbody cages, but there are virtually no comparative data for the different designs. Furthermore, most investigators have used animal models, which may have led to different results due to morphological variation in the end plates and articular facets. The objectives of the current study were to evaluate whether two different anterior cage designs (BAK and SynCage) performed differently with respect to immediate stabilization of the spine, whether the cages stabilized the spine significantly compared with its intact condition, and whether the addition of supplementary translaminar screw fixation further stabilized the spine. Stabilization was defined as a reduction in motion after insertion of an implant. METHODS: Twelve lumbar functional spinal units from human cadavera were tested under pure moments of flexion, extension, bilateral axial rotation, and bilateral lateral bending to a maximum of ten newton-meters. The relative intervertebral motions were measured, with use of an optoelectronic camera system, under three test conditions: with the spine intact, after insertion of anterior interbody cages, and after insertion of anterior interbody cages supplemented with translaminar screw fixation. Six specimens were tested for each type of cage: a bilateral, porous, threaded cylinder (BAK) and a central, porous, contoured implant with end-plate fit (SynCage). RESULTS: The cages performed in a similar manner in all directions of loading, with no significant differences between the two designs. The cages significantly stabilized the spine compared with its intact condition in flexion, axial rotation, and lateral bending (the median value for motion was 40, 48, and 29 percent of the value for the intact condition, respectively; p = 0.002 for all three directions). Compared with the cages alone, translaminar screw fixation provided no additional stabilizing effect in these directions but it significantly increased the stability of the spine in extension (the median value for motion was 34 percent of the value with the cages alone; p = 0.013). CONCLUSIONS: There were no differences in the stabilization provided by the two different cage designs. Use of the cages alone stabilized the spine in all directions except extension, and use of supplementary translaminar screw fixation provided additional stabilization only in extension. CLINICAL RELEVANCE: This study demonstrated that interbody cages do not stabilize the lumbar spine in extension, and this observation was not altered by the use of substantially different designs. If the lack of stabilization in extension is a clinical problem, possible solutions include the avoidance of extension postoperatively or the use of supplementary fixation.

Clinical study with recombinant interferon gamma versus interferon alpha-2c in patients with condylomata acuminata.

A multi-centre, randomized, open-label trial was conducted to evaluate the safety and efficacy of recombinant interferon (rIFN) alpha-2c versus rIFN gamma in patients with recurrent or persistent condylomata acuminata (CA). Thirty-three such patients were treated either with 6 micrograms rIFN alpha-2c or with 0.1 mg rIFN gamma (both equivalent to 2 x 10E6 IU), single dose, subcutaneously 3 times a week for 6 weeks. In case of no complete clearance at week 10, a second course of treatment with the other type of rIFN was given. There was no significant difference in the complete clearance proportions at week 10 between the two treatment groups (3/16 vs 6/17). No relapses occurred in these patients during the 16 weeks' follow-up. Further clearances during the follow-up resulted in a total complete clearance proportion of 14/33 at the end of study. The treatment was well tolerated. Repeated interferon therapy has its place in treating persistent or recurrent condylomas.

Does anterolateral cage insertion enhance immediate stabilization of the functional spinal unit? A biomechanical investigation.

STUDY DESIGN: The three-dimensional flexibility of six human lumbar functional spinal units was measured after the anterolateral insertion of an interbody cage. OBJECTIVES: To determine whether an interbody cage inserted from an anterolateral direction stabilizes the spine with respect to the intact state and to compare the finding with that from the same cage inserted from an anterior direction. SUMMARY OF BACKGROUND DATA: Several biomechanical studies have shown that interbody cages do not stabilize the spine in extension. It is suspected that this may be caused by the destruction of the anterior longitudinal ligament and anterior anulus fibrosus. METHODS: Six human cadaveric lumbar functional spinal units were tested under pure moments of flexion, extension, bilateral axial rotation, and bilateral lateral bending to a maximum of 10 Nm. The relative intervertebral motions were measured by an optoelectronic camera system with the spinal units in the intact condition, after discectomy, after anterolateral interbody cage stabilization, and with additional translaminar screw fixation. The implant used was a central, porous, contoured implant with endplate fit. The results were compared with those of a previous study, which used the same implant inserted from an anterior direction. RESULTS: The anterolateral cage insertion significantly decreased the motion in comparison with the intact situation in flexion and lateral bending, but not in extension or axial rotation. No differences were found between the anterior and anterolateral insertion approaches in flexion or extension, but differences were observed in axial rotation and lateral bending, in which the anterolateral approach resulted in more motion. Additional translaminar screw fixation reduced motion to below intact levels in all loading directions. None of the surgical procedures introduced asymmetrical behavior. CONCLUSIONS: Anterolateral cage insertion did not stabilize the spine in extension or axial rotation and was not different from the anterior approach in flexion and extension. Additional translaminar screw fixation stabilized in all directions.

Computer-assisted percutaneous transiliac approach to tumorous malformation of the sacrum.

The object of this article is to present a new, minimally invasive, percutaneous image-guided technique for surgery of tumorous malformation of the sacrum. Using one of the available CAS systems, we developed a navigable working tube through which various surgical tools may be very precisely introduced into the tumorous malformation. The tube allows us to obtain histological samples and also perform tumor resections. For sacral procedures, the working tube was introduced percutaneously into the affected area of the sacrum through the sacroiliac joint with computer assistance. For successful matching, small titanium screws were inserted into the sacrum and pelvis percutaneously before CT examination to give precise landmark points. We have used the method in 12 cases. The aim of the surgery in biopsy cases was to obtain samples for histological diagnoses of unknown tumors. In the cases of tumor resection (all were metastatic), the indication was to obtain neurological decompression and decreased local pain. The pain response was very effective in all cases. The transiliac percutaneous approach to the sacrum has proven to be a safe and well-designed procedure. It can even be performed under local anesthesia, and is thus a very effective minimally invasive tool for obtaining pain relief in cases of sacral metastasis involving the first, second, and third segments.