Dorsal root ganglion (DRG) neurons specifically project axons to central and peripheral targets according to their sensory modality. The Runt-related genes Runx1 and Runx3 are expressed in DRG neuronal subpopulations, suggesting that they may regulate the trajectories of specific axons. Here we report that Runx3-deficient (Runx3(-/-)) mice displayed severe motor uncoordination and that few DRG neurons synthesized the proprioceptive neuronal marker parvalbumin. Proprioceptive afferent axons failed to project to their targets in the spinal cord as well as those in the muscle. NT-3-responsive Runx3(-/-) DRG neurons showed less neurite outgrowth in vitro. However, we found no changes in the fate specification of Runx3(-/-) DRG neurons or in the number of DRG neurons that expressed trkC. Our data demonstrate that Runx3 is critical in regulating the axonal projections of a specific subpopulation of DRG neurons.

Background and Purpose-The purpose of the present study was to assess the incidence and clinical significance of the intraparenchymal hyperdense areas on the posttherapeutic CT scan just after intra-arterial reperfusion therapy. Methods-Seventy-seven patients with acute middle cerebral artery occlusion were studied prospectively with posttherapeutic CT. Hyperdense areas were classified into three groups: those in the lentiform nucleus, insular cortex and cerebral cortex. We investigated the incidence of hyperdense areas and hemorrhagic transformations and assessed whether location of hyperdense areas may play a role in the incidence of hemorrhagic transformations. We also evaluated correlation between early CT signs and hyperdense areas. Results-Forty-five hyperdense areas were seen in 37 of the 77 patients (48.1%): 19 of the 45 (42.2%) were confirmed to be hematomas themselves, 6 (13.4%) showed later conversion to petechial hemorrhages, and 20 (44.4%) showed rapid disappearance without hemorrhagic transformations. Eleven of the 37 patients (29.7%) had neurological worsening due to massive hematoma (symptomatic hemorrhage), whereas none of the 40 patients without hyperdense areas had symptomatic hemorrhage. The incidence of hemorrhage among hyperdense areas was significantly lower in the insular cortex than in the other 2 regions (PϽ0.01). On the other hand, hyperdense areas in the lentiform nucleus had a significantly higher incidence of neurological worsening (PϽ0.05). There was a significant correlation between early CT signs and hyperdense areas (PϽ0.0001). Conclusions-The presence of hyperdense areas was a significant risk factor for severe hemorrhagic transformations, although only 29.7% of patients with hyperdense areas had symptomatic hemorrhage. On the contrary, the absence of hyperdense areas was a reliable negative predictor for symptomatic hemorrhage.

Background and Purpose-The purpose of this study was to evaluate the safety and efficacy of direct percutaneous transluminal angioplasty (PTA) for patients with acute middle cerebral artery (MCA) trunk occlusion. Methods-Over the past 9 years, a total of 70 patients with acute MCA trunk occlusion were treated with intra-arterial reperfusion therapy. In the last 5 years, 34 patients were treated with direct PTA, and subsequent thrombolytic therapy was added if necessary for distal embolization. The other 36 patients, mainly in the first 4 years, were treated with thrombolytic therapy alone and were used as controls. Pretherapeutic neurological status was evaluated with National Institutes of Health Stroke Scale scores. The modified Rankin Scale (mRS) was used to assess clinical outcome at 90 days. Results-There were no significant differences in pretherapeutic National Institutes of Health Stroke Scale score and duration of ischemia between the 2 groups. The rate of partial or complete recanalization in the PTA group was 91.2%, whereas that in the thrombolysis-alone group was 63.9% (PϽ0.01). The incidence of large parenchymal hematoma with neurological deterioration in the PTA group was 2.9%, while that in the thrombolysis-alone group was 19.4% (Pϭ0.03).Although direct PTA did not improve the rate of favorable outcome (mRS score 0 or 1; 41.7% for the thrombolysis-alone group versus 52.9% for the PTA group; Pϭ0.48), outcome in terms of independence (mRS score 0, 1, 2) was significantly better in the PTA group (73.5%) than in the thrombolysis-alone group (50.0%; Pϭ0.04). Conclusions-Although definitive conclusions on the comparative merits of these 2 therapies cannot be drawn because of an open trial, direct PTA may be an effective alternative option to intra-arterial thrombolysis for acute MCA trunk occlusion.

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Chondroitin sulfate proteoglycans (CSPGs) inhibit axonal growth, and treatment with chondroitinase ABC promotes axonal regeneration in some models of central nervous system (CNS) injury. The aims of this study were (1) to compare the spatiotemporal appearance of CSPG expression between spinal cord contusion and hemisection models, and (2) to evaluate chondroitinase treatment effects on axonal regrowth in the two injury models. After hemisection, CSPG-immunoreactivity (IR) in the injury site rose to peak levels at 18 days but then decreased dramatically by 49 days; in contrast, CSPG-IR remained high for at least 49 days after contusion. After hemisection, many anterogradely labeled corticospinal tract (CST) axons remained close to CSPG-rich lesion sites, but after contusion, most CST axons retracted by approximately 1 mm rostral from the rostral-most CSPG-rich cyst. Intraspinal injection of chondroitinase at 0, 1, 2, and 4 weeks following injury dramatically reduced CSPG-IR in both injury models within 4 days, and CSPG-IR remained low for at least 3 weeks. After the chondroitinase treatment, many axons grew around the lesion site in hemisected spinal cords but not in contused spinal cords. We propose that improved axonal growth in hemisected spinal cords is due to decreased inhibition resulting from degradation of CSPGs located adjacent to severed CST axons. However, in spinal cord contusions, retracted CST axons fail to grow across gliotic regions that surround CSPG-rich injury sites despite efficient degradation with chondroitinase, suggesting that other inhibitors of axonal growth persist in the gliotic regions.