Search

BACKGROUND: Brain repair mechanisms fail to promote recovery after stroke and approaches to induce brain regeneration are scarce. Mesenchymal stem cells (MSC) are thought to be a promising therapeutic option. However, their efficacy is not fully elucidated and the mechanism underlying their effect is not known. METHODS: The middle cerebral artery occlusion (MCAO) model was utilized to determine the efficacy of interferon-γ-activated mesenchymal stem cells (aMSCγ) as an acute therapy for stroke. aMSCγ were intravenously administered to rats three hours after MCAO and functional recovery was assessed using the modified Neurological Severity Score (mNSS), open field analysis, and magnetic resonance imaging. Alterations in post-stroke inflammation, neurogenesis, and oligodendrogenesis were analyzed using biochemical, immunofluorescence, and stereological techniques. Mass spectrometry was used to analyze the MSC secretome. RESULTS: Here we show that treatment with aMSCγ is a more potent therapy for stroke than naïve MSC (nMSC). aMSCγ treatment results in significant functional recovery assessed by the mNSS and open field analysis compared to vehicle-treated animals. aMSCγ-treated animals showed significant reductions in infarct size and inhibition of microglial activation. We show that aMSCγ treatment suppresses the hypoxia-induced microglial pro-inflammatory phenotype more effectively than treatment with nMSC. Importantly, treatment with aMSCγ induces recruitment and differentiation of oligodendrocyte progenitor cells to myelin-producing oligodendrocytes in vivo. To elucidate the mechanism underlying high efficacy of aMSCγ therapy, we examined the secretome of aMSCγ and compared it to nMSC. Intriguingly, we found that aMSCγ but not nMSC upregulate neuron-glia antigen 2, (NG2), an important extracellular signal and a hallmark protein of oligodendrocyte progenitor cells (OPCs). CONCLUSIONS: These results suggest that activation of MSC with interferon-γ induces a potent pro-regenerative, pro-myelinating, and anti-inflammatory phenotype of these cells, which increases the potency of aMSCγ as an effective therapy for ischemic stroke. The unraveling of the secretome of aMSCγ may help move the field towards a better understanding of the potential of MSCs as a therapy for stroke.

INTRODUCTION Although primarily a respiratory disorder, the coronavirus pandemic has paralyzed almost all aspects of healthcare delivery. Neurosurgeons provide critical care and their role in this pandemic is necessary and yet evolving. METHODS Through professional registries and internet resources, we surveyed neurosurgeons from around the world. We looked at the national burden of illness, perception of preparedness, cancellation of clinics, surgeries and cessation of research and educational activities. Chi-square, Fisher's exact tests, and multivariate logistic regression model were used to analyze variables. RESULTS Our survey was completed on April 3, 2020, and was well-received (661 completed, 60.7% response rate, 96 nations). Neurosurgeons in affluent nations still lacked adequate resources to combat this pandemic primarily due to lack of preparedness and insufficient medical equipment. The challenges to lower-income nations were similar but also included knowledge dissemination and inadequate resources. Hospital preparedness was central to effective healthcare delivery but also influenced the cancellation of surgeries and clinics. The impact on education, conferences and research was also significant. CONCLUSION Neurosurgical disorders are significant casualties of the COVID-19 pandemic. Reduction of services, lack of preparedness, inadequate education, insufficient supplies and resources are important contributors. Improved preparedness requires careful planning, real-time surveillance and allocation of resources. This is more critical in poorer nations.