Peripheral nerve injury can lead to great morbidity in those afflicted, ranging from sensory loss, motor loss, chronic pain, or a combination of deficits. Over time, research has investigated neuronal molecular mechanisms implicated in nerve damage, classified nerve injury, and developed surgical techniques for treatment. Despite these advancements, full functional recovery remains less than ideal. In this review, we discuss historical aspects of peripheral nerve injury and introduce nerve transfer as a therapeutic option, as well as an adjunct therapy to transplantation of Schwann cells and their stem cell derivatives for repair of the damaged nerve. This review furthermore, will provide an elaborated discussion on the sources of Schwann cells, including sites to harvest their progenitor and stem cell lines. This reflects the accessibility to an additional, concurrent treatment approach with nerve transfers that, predicated on related research, may increase the efficacy of the current approach. We then discuss the experimental and clinical investigations of both Schwann cells and nerve transfer that are underway. Lastly, we provide the necessary consideration that these two lines of therapeutic approaches should not be exclusive, but conversely, should be pursued as a combined modality given their mutual role in peripheral nerve regeneration.

Modified mesenchymal stromal cells (MSCs) display a unique mechanism of action during the repair phase of traumatic brain injury by exhibiting the ability to build a biobridge between the neurogenic niche and the site of injury. Immunohistochemistry and laser capture assay have visualized this biobridge in the area between the neurogenic subventricular zone and the injured cortex. This biobridge expresses high levels of extracellular matrix metalloproteinases (MMPs), which are initially co-localized with a stream of transplanted MSCs, but later this region contains only few to non-detectable grafts and becomes overgrown by newly recruited host cells. We have reported that long-distance migration of host cells from the neurogenic niche to the injured brain site can be attained via these transplanted stem cell-paved biobridges, which serve as a key regenerative process for the initiation of endogenous repair mechanisms. Thus, far the two major schools of discipline in stem cell repair mechanisms support the idea of “cell replacement” and the bystander effects of “trophic factor secretion.” Our novel observation of stem cell-paved biobridges as pathways for directed migration of host cells from neurogenic niche toward the injured brain site adds another mode of action underlying stem cell therapy. More in-depth investigations on graft-host interaction will likely aid translational research focused on advancing this stem cell-paved biobridge from its current place, as an equally potent repair mechanism as cell replacement and trophic factor secretion, into a new treatment strategy for traumatic brain injury and other neurological disorders.

BACKGROUND: Multiple studies have reported higher rates of glioma in areas with higher socioeconomic status (SES) but to the authors' knowledge have not stratified by other factors, including race/ethnicity or urban versus rural location. METHODS: The authors identified the average annual age-adjusted incidence rates and calculated hazard ratios for death for gliomas of various subtypes, stratified by a county-level index for SES, race/ethnicity, US region, and rural versus urban status. RESULTS: Rates of glioma were highest in counties with higher SES (rate ratio, 1.18; 95% CI, 1.15-1.22 comparing the highest with the lowest quintiles [P < .001]). Stratified by race/ethnicity, higher rates in high SES counties persisted for white non-Hispanic individuals. Stratified by rural versus urban status, differences in incidence by SES were more pronounced among urban counties. Survival was higher for residents of high SES counties after adjustment for age and extent of surgical resection (hazard ratio, 0.82; 95% CI, 0.76-0.87 comparing the highest with the lowest quintile of SES [P < .001]). Survival was higher among white Hispanic, black, and Asian/Pacific Islander individuals compared with white non-Hispanic individuals, after adjustment for age, SES, and extent of surgical resection, and when restricted to those individuals with glioblastoma who received radiation and chemotherapy. CONCLUSIONS: The incidence of glioma was higher in US counties of high compared with low SES. These differences were most pronounced among white non-Hispanic individuals and white Hispanic individuals residing in urban areas. Better survival was observed in high SES counties, even when adjusting for extent of surgical resection, and when restricted to those who received radiation and chemotherapy for glioblastoma. Differences in incidence and survival were associated with SES and race, rather than rural versus urban status. Cancer 2019;125:3390-3400.

ImportanceThe role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well.ObjectiveTo evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well.Design, Setting, and ParticipantsThis retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or medical management beyond 24 hours of last known well.InterventionsEndovascular thrombectomy or medical management (control).Main Outcomes and MeasuresPrimary outcome was functional independence (modified Rankin Scale score 0-2). Mortality and symptomatic intracranial hemorrhage (sICH) were safety outcomes. Propensity score (PS)–weighted multivariable logistic regression analyses were adjusted for prespecified clinical characteristics, perfusion parameters, and/or Alberta Stroke Program Early CT Score (ASPECTS) and were repeated in subsequent 1:1 PS-matched cohorts.ResultsOf 301 patients (median [IQR] age, 69 years [59-81]; 149 female), 185 patients (61%) received EVT and 116 (39%) received medical management. In adjusted analyses, EVT was associated with better functional independence (38% vs control, 10%; inverse probability treatment weighting adjusted odds ratio [IPTW aOR], 4.56; 95% CI, 2.28-9.09; P &amp;lt; .001) despite increased odds of sICH (10.1% for EVT vs 1.7% for control; IPTW aOR, 10.65; 95% CI, 2.19-51.69; P = .003). This association persisted after PS-based matching on (1) clinical characteristics and ASPECTS (EVT, 35%, vs control, 19%; aOR, 3.14; 95% CI, 1.02-9.72; P = .047); (2) clinical characteristics and perfusion parameters (EVT, 35%, vs control, 17%; aOR, 4.17; 95% CI, 1.15-15.17; P = .03); and (3) clinical characteristics, ASPECTS, and perfusion parameters (EVT, 45%, vs control, 21%; aOR, 4.39; 95% CI, 1.04-18.53; P = .04). Patients receiving EVT had lower odds of mortality (26%) compared with those in the control group (41%; IPTW aOR, 0.49; 95% CI, 0.27-0.89; P = .02).Conclusions and RelevanceIn this study of treatment beyond 24 hours of last known well, EVT was associated with higher odds of functional independence compared with medical management, with consistent results obtained in PS-matched subpopulations and patients with presence of mismatch, despite increased odds of sICH. Our findings support EVT feasibility in selected patients beyond 24 hours. Prospective studies are warranted for confirmation.