scholarly journals An implantable human stem cell-derived tissue-engineered rostral migratory stream for directed neuronal replacement

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
John C. O’Donnell ◽  
Erin M. Purvis ◽  
Kaila V. T. Helm ◽  
Dayo O. Adewole ◽  
Qunzhou Zhang ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Rostral Migratory Stream ◽  
Brain Lesions ◽  
New Approach ◽  
Neuroblast Migration ◽  
Human Gingiva ◽  
Neuronal Replacement ◽  
Neuroregenerative Medicine ◽  
Migratory Stream

AbstractThe rostral migratory stream (RMS) facilitates neuroblast migration from the subventricular zone to the olfactory bulb throughout adulthood. Brain lesions attract neuroblast migration out of the RMS, but resultant regeneration is insufficient. Increasing neuroblast migration into lesions has improved recovery in rodent studies. We previously developed techniques for fabricating an astrocyte-based Tissue-Engineered RMS (TE-RMS) intended to redirect endogenous neuroblasts into distal brain lesions for sustained neuronal replacement. Here, we demonstrate that astrocyte-like-cells can be derived from adult human gingiva mesenchymal stem cells and used for TE-RMS fabrication. We report that key proteins enriched in the RMS are enriched in TE-RMSs. Furthermore, the human TE-RMS facilitates directed migration of immature neurons in vitro. Finally, human TE-RMSs implanted in athymic rat brains redirect migration of neuroblasts out of the endogenous RMS. By emulating the brain’s most efficient means for directing neuroblast migration, the TE-RMS offers a promising new approach to neuroregenerative medicine.

scholarly journals A new function for Prokineticin 2: recruitment of SVZ-derived neuroblasts to the injured cortex in a mouse model of traumatic brain injury

2018 ◽  
Author(s):  
Mayara Vieira Mundim ◽  
Laura Nicoleti Zamproni ◽  
Agnes Araújo Sardinha Pinto ◽  
Layla Testa Galindo ◽  
André Machado Xavier ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Subventricular Zone ◽  
Brain Injuries ◽  
Rostral Migratory Stream ◽  
Subgranular Zone ◽  
Prokineticin 2 ◽  
Migratory Stream

AbstractTraumatic brain injury is an important cause of mortality and morbidity all over the world. After the initial injury there is a cascade of cellular and molecular events that ultimately lead to cell death. Therapies aim not only to counteract these mechanisms but also to replenish the lost cell population in order to achieve a better recovery. The adult mammal brain in not as plastic as the postnatal, but it has at least two neurogenic regions that maintains physiological functions in the brain; the subgranular zone of the dentate gyrus of the hippocampus, which produces neurons that integrate locally, and the subventricular zone (SVZ) of the lateral ventricles, that produces neuroblasts that migrate through the rostral migratory stream (RMS) to the olfactory bulbs. Brain injuries, as well as neurodegenerative diseases, induce the SVZ to respond by increasing cell proliferation and migration to the injured areas. Here we report that SVZ cells migrate to the injured cortex after traumatic brain injury in mice, and that the physiological RMS migration is not impaired. We also show that Prokineticin 2 (PROK2), a chemokine important for the olfactory bulb neurogenesis by promoting the directional migration of neuroblasts, is induced in the injured cortex. Using PROK2 receptor antagonist and recombinant PROK2 we show for the first time that PROK2 can directionally attract SVZ cells in vitro and in vivo. The data we present here links one more element of the inflammatory process, PROK2 secreted by microglia, to the attempt to regenerate an acutely injured mammalian cortex.AbbreviationsSGZsubgranular zoneSVZsubventricular zoneRMSrostral migratory streamPROK2Prokineticin 2

scholarly journals Cellular composition and organization of the subventricular zone and rostral migratory stream in the adult and neonatal common marmoset brain

2011 ◽  
Vol 519 (4) ◽  
pp. 690-713 ◽  
Author(s):  
Kazunobu Sawamoto ◽  
Yuki Hirota ◽  
Clara Alfaro-Cervello ◽  
Mario Soriano-Navarro ◽  
Xiaoping He ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Common Marmoset ◽  
Rostral Migratory Stream ◽  
Cellular Composition ◽  
Migratory Stream

scholarly journals The Subventricular Zone Continues to Generate Corpus Callosum and Rostral Migratory Stream Astroglia in Normal Adult Mice

2015 ◽  
Vol 35 (9) ◽  
pp. 3756-3763 ◽  
Author(s):  
J. Sohn ◽  
L. Orosco ◽  
F. Guo ◽  
S.-H. Chung ◽  
P. Bannerman ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Subventricular Zone ◽  
Rostral Migratory Stream ◽  
Normal Adult ◽  
Adult Mice ◽  
Migratory Stream

scholarly journals Secretagogin-dependent matrix metalloprotease-2 release from neurons regulates neuroblast migration

2017 ◽  
Vol 114 (10) ◽  
pp. E2006-E2015 ◽  
Author(s):  
János Hanics ◽  
Edit Szodorai ◽  
Giuseppe Tortoriello ◽  
Katarzyna Malenczyk ◽  
Erik Keimpema ◽  
...  
Keyword(s):  
Annexin V ◽  
Therapeutic Benefit ◽  
Mouse Genetics ◽  
Matrix Metalloprotease ◽  
Loss Of Function ◽  
Neuroblast Migration ◽  
Sensor Protein ◽  
Migratory Stream

The rostral migratory stream (RMS) is viewed as a glia-enriched conduit of forward-migrating neuroblasts in which chemorepulsive signals control the pace of forward migration. Here we demonstrate the existence of a scaffold of neurons that receive synaptic inputs within the rat, mouse, and human fetal RMS equivalents. These neurons express secretagogin, a Ca2+-sensor protein, to execute an annexin V-dependent externalization of matrix metalloprotease-2 (MMP-2) for reconfiguring the extracellular matrix locally. Mouse genetics combined with pharmacological probing in vivo and in vitro demonstrate that MMP-2 externalization occurs on demand and that its loss slows neuroblast migration. Loss of function is particularly remarkable upon injury to the olfactory bulb. Cumulatively, we identify a signaling cascade that provokes structural remodeling of the RMS through recruitment of MMP-2 by a previously unrecognized neuronal constituent. Given the life-long presence of secretagogin-containing neurons in human, this mechanism might be exploited for therapeutic benefit in rescue strategies.

scholarly journals Angiogenin in the Neurogenic Subventricular Zone After Stroke

2021 ◽  
Vol 12 ◽  
Author(s):  
Marina Gabriel-Salazar ◽  
Ting Lei ◽  
Alba Grayston ◽  
Carme Costa ◽  
Esperanza Medina-Gutiérrez ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Cell Function ◽  
Stroke Recovery ◽  
Post Stroke ◽  
Neuroblast Migration ◽  
Permanent Occlusion ◽  
Repair Mechanisms ◽  
Exercise Induced ◽  
First Time

Ischemic stroke is a leading cause of death and disability worldwide with effective acute thrombolytic treatments. However, brain repair mechanisms related to spontaneous or rehabilitation-induced recovery are still under investigation, and little is known about the molecules involved. The present study examines the potential role of angiogenin (ANG), a known regulator of cell function and metabolism linked to neurological disorders, focusing in the neurogenic subventricular zone (SVZ). Angiogenin expression was examined in the mouse SVZ and in SVZ-derived neural stem cells (NSCs), which were exposed to exogenous ANG treatment during neurosphere formation as well as in other neuron-like cells (SH-SY5Y). Additionally, male C57Bl/6 mice underwent a distal permanent occlusion of the middle cerebral artery to study endogenous and exercise-induced expression of SVZ-ANG and neuroblast migration. Our results show that SVZ areas are rich in ANG, primarily expressed in DCX+ neuroblasts but not in nestin+NSCs. In vitro, treatment with ANG increased the number of SVZ-derived NSCs forming neurospheres but could not modify SH-SY5Y neurite differentiation. Finally, physical exercise rapidly increased the amount of endogenous ANG in the ipsilateral SVZ niche after ischemia, where DCX-migrating cells increased as part of the post-stroke neurogenesis process. Our findings position for the first time ANG in the SVZ during post-stroke recovery, which could be linked to neurogenesis.

scholarly journals Neuronal precursor cells with dopaminergic commitment in the rostral migratory stream of the mouse

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kerstin Schweyer ◽  
Corinna Rüschoff-Steiner ◽  
Oscar Arias-Carrión ◽  
Wolfgang H. Oertel ◽  
Thomas W. Rösler ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Cell Layer ◽  
Granular Cell ◽  
Rostral Migratory Stream ◽  
Physical Barrier ◽  
Short Term ◽  
Term Survival ◽  
Granular Cell Layer ◽  
Migratory Stream

Abstract Neuroblasts born in the subventricular zone of adult mammals migrate via the rostral migratory stream into the granular cell layer or periglomerular layer of the olfactory bulb to differentiate into interneurons. To analyze if new neurons in the granular cell layer or periglomerular layer have different origins, we inserted a physical barrier into the rostral migratory stream, depleted cell proliferation with cytarabine infusions, labeled newborn cells with bromodeoxyuridine, and sacrificed mice after short-term (0, 2, or 14 days) or long-term (55 or 105 days) intervals. After short-term survival, the subventricular zone and rostral migratory stream rapidly repopulated with bromodeoxyuridine+ cells after cytarabine-induced depletion. Nestin, glial fibrillary acidic protein and the PAX6 were expressed in bromodeoxyuridine+ cells within the rostral migratory stream downstream of the physical barrier. After long-term survival after physical barrier implantation, bromodeoxyuridine+ neurons were significantly reduced in the granular cell layer, but bromodeoxyuridine+ and dopaminergic neurons in the periglomerular layer remained unaffected by the physical barrier. Thus, newborn neurons for the granular cell layer are mainly recruited from neural stem cells located in the subventricular zone, but new neurons for the periglomerular layer with dopaminergic predisposition can rise as well from neuronal stem or precursor cells in the rostral migratory stream.

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