Mesenchymal stromal stem cells (MSCs) isolated from adult tissues offer tangible potential for regenerative medicine, given their feasibility for autologous transplantation. MSC research shows encouraging results in experimental stroke, amyotrophic lateral sclerosis, and neurotrauma models. However, further translational progress has been hampered by poor MSC graft survival, jeopardizing cellular and molecular bases for neural repair in vivo. We have devised an adult human bone marrow MSC (hMSC) delivery formula by investigating molecular events involving hMSCs incorporated in a uniquely designed poly(lactic-co-glycolic) acid scaffold, a clinically safe polymer, following inflammatory exposures in a dorsal root ganglion organotypic coculture system. Also, in rat T9-T10 hemisection spinal cord injury (SCI), we demonstrated that the tailored scaffolding maintained hMSC stemness, engraftment, and led to robust motosensory improvement, neuropathic pain and tissue damage mitigation, and myelin preservation. The scaffolded nontransdifferentiated hMSCs exerted multimodal effects of neurotrophism, angiogenesis, neurogenesis, antiautoimmunity, and antiinflammation. Hindlimb locomotion was restored by reestablished integrity of submidbrain circuits of serotonergic reticulospinal innervation at lumbar levels, the propriospinal projection network, neuromuscular junction, and central pattern generator, providing a platform for investigating molecular events underlying the repair impact of nondifferentiated hMSCs. Our approach enabled investigation of recovery neurobiology components for injured adult mammalian spinal cord that are different from those involved in normal neural function. The uncovered neural circuits and their molecular and cellular targets offer a biological underpinning for development of clinical rehabilitation therapies to treat disabilities and complications of SCI.spinal cord injury | recovery neurobiology | mesenchymal stromal stem cell | PLGA | locomotion R epair of neurotrauma, stroke, and neurodegenerative diseases remains an unmet medical demand because of their pathophysiological complexity and the limited spontaneous healing capacity of adult mammalian CNS. Human mesenchymal stromal stem cells (hMSCs) offer autologous transplantation feasibility (1-4) and have been studied both experimentally and clinically for traumatic brain injury (TBI) and spinal cord injury (SCI) (5-8). Although MSCs possess homeostatic and proneurogenic activities (7, 9), studies relying on neural transdifferentiation (i.e., putative differentiations of MSCs into neural cells without reentering the pluripotency phase) did not show long-term functional improvement in SCI models. The poor outcomes were attributed mainly to suboptimal survival of MSCs, leaving key therapeutic mechanisms undetermined (10). We previously established a 3D cell delivery technology by seeding neural stem cells (NSCs) in biodegradable polymer scaffolds that significantly improved donor efficacy and enabled investigation of NSC repair mechanisms in t...

Objective The objective was to determine the impact of the COVID-19 pandemic on operative case volume in 8 US neurosurgical residency training programs in early 2020 and to survey these programs regarding training activities during this period. Methods A retrospective review was conducted of monthly operative case volumes and types for 8 residency programs for 2019 and January-April 2020. Cases were grouped as elective cranial, elective spine, and non-elective emergent cases. Programs were surveyed regarding residents’ perceptions of the impact of COVID-19 on surgical training, didactics, and research participation. Data was analyzed for individual programs and pooled across programs. Results Across programs, the 2019 monthly case average was 211 (SD ± 82); 2020 average case volumes for January, February, March, and April were 228±93, 214±84, 180±73, and 107±45, respectively. Compared with 2019, March and April 2020 average cases declined 15% (p=0.003) and 49% (p=0.002), respectively. COVID-19 affected surgical case volume for all programs; 75% reported didactics negatively affected, and 90% reported COVID-19 resulted in increased research time. Several neurosurgery residents have required COVID-19 testing, however, to our knowledge, only one resident from the participating programs tested positive. Conclusions This study documents a significant reduction in operative volume in 8 neurosurgery residency training programs in early 2020. During this time, neurosurgery residents engaged in online didactics and research-related activities, reporting increased research productivity. Residency programs should collect data to determine the educational impact of the pandemic on resident operative case volumes, identify deficiencies, and develop plans to mitigate any effects.

Intervertebral disk (IVD) degeneration is a common, chronic, and complex degeneration process that frequently leads to back pain and disability, resulting in a major public health issue. In this review we describe biological therapies under preclinical or clinical development with an emphasis on stem cell-based multimodal approaches that target prevention and treatment of IVD degeneration. Systematical review of the basic science and clinical literature was performed to summarize the current status of devising biological approaches to treating IVD degeneration. Since the exact mechanisms underlying IVD degeneration have not yet been fully elucidated and conservative managements appear to be mostly ineffective, current surgical treatment focuses on removal of the pathological disk tissues combined with spinal fusion. The treatment options, however, often produce insufficient efficacy and even serious complications. Therefore, there have been growing demands and endeavors for developing novel regenerative biology-guided strategies for repairing the IVD via delivery of exogenous growth factors, introduction of therapeutic genes, and transplantation of stem cells, or combinatorial therapies. Overall, the data suggest that when applied under a recovery neurobiology principle, multimodal regimens comprising ex vivo engineered stem cell-based disks hold a high potential promise for efficacious clinical translations.

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Cervical spondylotic myelopathy (CSM) is the chronic and slow deterioration of cervical spinal cord function. The pathophysiology of this condition is multifactorial, including compression, repetitive trauma, and vascular compromise of the spinal cord. Clinically, it presents as a progressive decline in patients’ appendicular neurological function. The natural history of this disease varies but, it is well-known that the duration and degree of compression correlate negatively with prognosis. A mild degree of CSM tends to stabilize with potential improvement over time while more severe CSM tends to progress. Surgical intervention has shown to positively alter the natural history of the disease by halting the progression with some restoration of function. Ossification of the posterior longitudinal ligament (OPLL) is a chronic disease that results in progressive ossification of the posterior longitudinal ligament of the spine. It commonly affects the cervical spine. The etiology is multifactorial in nature, including genetic and environmental factors. The progressive nature of this condition and the resultant cervical spinal stenosis make it one of the main causes of cervical myelopathy (CM). There is no medical therapy for this disease, and surgery is reserved for patients with CM caused by spinal cord compression. In this article, we review the different aspects of the natural history of both CSM and OPLL.

OBJECTIVE Cognitive dysfunction occurs in up to 70% of aneurysmal subarachnoid hemorrhage (aSAH) survivors. Low-dose intravenous heparin (LDIVH) infusion using the Maryland protocol was recently shown to reduce clinical vasospasm and vasospasm-related infarction. In this study, the Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive changes in aSAH patients treated with the Maryland LDIVH protocol compared with controls. METHODS A retrospective analysis of all patients treated for aSAH between July 2009 and April 2014 was conducted. Beginning in 2012, aSAH patients were treated with LDIVH in the postprocedural period. The MoCA was administered to all aSAH survivors prospectively during routine follow-up visits, at least 3 months after aSAH, by trained staff blinded to treatment status. Mean MoCA scores were compared between groups, and regression analyses were performed for relevant factors. RESULTS No significant differences in baseline characteristics were observed between groups. The mean MoCA score for the LDIVH group (n = 25) was 26.4 compared with 22.7 in controls (n = 22) (p = 0.013). Serious cognitive impairment (MoCA ≤ 20) was observed in 32% of controls compared with 0% in the LDIVH group (p = 0.008). Linear regression analysis demonstrated that only LDIVH was associated with a positive influence on MoCA scores (β = 3.68, p =0.019), whereas anterior communicating artery aneurysms and fevers were negatively associated with MoCA scores. Multivariable linear regression analysis resulted in all 3 factors maintaining significance. There were no treatment complications. CONCLUSIONS This preliminary study suggests that the Maryland LDIVH protocol may improve cognitive outcomes in aSAH patients. A randomized controlled trial is needed to determine the safety and potential benefit of unfractionated heparin in aSAH patients.

5FC, 5-fluorocytosineBBB, Basso, Beattie, and BresnahanCD, cytosine deaminaseDP, diastolic blood pressureGCV, ganciclovir; hNSCs, human neural stem cellsISCG, intramedullary spinal cord gliomasMAP, mean arterial blood pressureNSCs, neural stem cellsSP, systolic blood pressureTK, thymidine kinase.

Intrathecal baclofen has been suggested as an effective and safe treatment for intractable spasticity and dystonia. Techniques of lumbar and intraventricular catheter placement have been previously described. The purpose of this study was to describe a technique to implant catheters for intrathecal baclofen infusion through C1–2 puncture.Four of 5 consecutively treated patients underwent successful placement of catheters for intrathecal baclofen. There were no instances of infection, CSF leak, or catheter migration seen during a follow-up period of at least 6 months; furthermore, there were no occurrences of vertebral artery or spinal cord injury. All patients had an effective stabilization or reduction of their upper-extremity, lower-extremity, or trunk tone. There were no cases of worsening hypertonia.The authors’ preliminary experience with C1–2 puncture for placement of the intrathecal baclofen catheter seems to indicate that this is a safe and efficacious technique. Lessons learned from the failed attempt at C1–2 puncture will be delineated.