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.