Recent studies have indicated that bone marrow stromal cells (BMSC) may improve neurological function when transplanted into an animal model of CNS disorders, including cerebral infarct. However, there are few studies that evaluate the therapeutic benefits of intracerebral and intravenous BMSC transplantation for cerebral infarct. This study was aimed to clarify the favorable route of cell delivery for cerebral infarct in rats. The rats were subjected to permanent middle cerebral artery occlusion. The BMSC were labeled with near infrared (NIR)-emitting quantum dots and were transplanted stereotactically (1 × 10⁶ cells) or intravenously (3 × 10⁶ cells) at 7 days after the insult. Using in vivo NIR fluorescence imaging technique, the behaviors of BMSC were serially visualized during 4 weeks after transplantation. Motor function was also assessed. Immunohistochemistry was performed to evaluate the fate of the engrafted BMSC. Intracerebral, but not intravenous, transplantation of BMSC significantly enhanced functional recovery. In vivo NIR fluorescence imaging could clearly visualize their migration toward the cerebral infarct during 4 weeks after transplantation in the intracerebral group, but not in the intravenous, group. The BMSC were widely distributed in the ischemic brain and some of them expressed neural cell markers in the intracerebral group, but not in the intravenous group. These findings strongly suggest that intravenous administration of BMSC has limited effectiveness at clinically relevant timing and intracerebral administration should be chosen for patients with ischemic stroke, although further studies would be warranted to establish the treatment protocol.
IMPORTANCE The application of optimal forces between surgical instruments and tissue is fundamental to surgical performance and learning. To date, this force has not been measured clinically during the performance of microsurgery. OBJECTIVES To establish a normative catalog of force profiles during the performance of surgery, to compare force variables among surgeons with different skill levels, and to evaluate whether such a force-based metric determines or differentiates skill level. DESIGN, SETTING, AND PARTICIPANTS Through installation of strain gauge sensors, a force-sensing bipolar forceps was developed, and force data were obtained from predetermined surgical tasks at the Foothills Medical Centre, University of Calgary, a tertiary care center that serves Southern Alberta, Canada. Sixteen neurosurgeons (3 groups: novice, intermediate, and experienced) performed surgery on 26 neurosurgical patients with various conditions. Normative baseline force ranges were obtained using the force profiles (mean and maximum forces and force variability) from the experienced surgeons. Standardized force profiles and force errors (high force error [HFE], low force error [LFE], and force variability error [FVE]) were analyzed and compared among surgeons with different skill levels. MAIN OUTCOMES AND MEASURES Each trial of the forceps use was termed successful or unsuccessful. The force profiles and force errors were analyzed and compared. RESULTS This study included 26 patients (10 [38%] male and 16 [62%] female; mean [SD] age, 43 [15] years) undergoing neurosurgery by 16 surgeons (6 in the novice group, 5 in the intermediate group, and 5 in the experienced group). Unsuccessful trial-incomplete significantly correlated with LFE and FVE, and unsuccessful trial-bleeding correlated with HFE and FVE. The force strengths exerted by novice surgeons were significantly higher than those of experienced surgeons (0.74 vs 0.00; P < .001), and force variability decreased from novice (0.43) to intermediate (0.28) to experienced (0.00) surgeons; however, these differences varied among surgical tasks. The rate of HFE and FVE inversely correlated with surgeon level of experience (HFE, 0.27 for novice surgeons, 0.12 for intermediate surgeons, and 0.05 for experienced surgeons; FVE, 0.16 for novice surgeons, 0.10 for intermediate surgeons, and 0.05 for experienced surgeons). The rate of LFE significantly increased in intermediate (0.12) and novice (0.10) surgeons compared with experienced surgeons (0.04; P < .001). There was no difference in LFE between intermediate and novice surgeons. Stepwise discriminant analysis revealed that combined use of these error rates could accurately discriminate the groups (87.5%). CONCLUSIONS AND RELEVANCE Force-sensing bipolar forceps and force analysis may help distinguish surgeon skill level, which is particularly important as surgical education shifts to a competency-based paradigm.
NIR fluorescence imaging is valuable in monitoring the behaviors of donor cells in the rodent brain. The results would allow new opportunities to develop noninvasive NIR fluorescence imaging as a modality to track the BMSCs transplanted into the brain.
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