Inflammation without neuronal death triggers striatal neurogenesis comparable to stroke

What is your doctor doing to mimic this in your stroke recovery? ANYTHING AT ALL?
Sounds like something useful for us.
Inflammation without neuronal death triggers striatal neurogenesis comparable to stroke

• Katie Z. Chapman^{a, 1},
• Ruimin Ge^{a, 1},
• Emanuela Monni^a,
• Jemal Tatarishvili^a,
• Henrik Ahlenius^b,
• Andreas Arvidsson^{a, c},
• Christine T. Ekdahl^d,
• Olle Lindvall^{a, 2},
• Zaal Kokaia^{a, , 2,}

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doi:10.1016/j.nbd.2015.08.013

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Highlights

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LPS-induced inflammation without neuronal loss triggers striatal neurogenesis

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Magnitude of striatal neurogenesis is similar to that after stroke-induced injury

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Microarray on sorted microglia identifies factors potentially regulating neurogenesis

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CXCL13 is upregulated in microglia and increases neuroblast migration in vitro

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Microglia-derived CXCL13, acting through CXCR5, might be neuroprotective in stroke

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Abstract

Ischemic stroke triggers neurogenesis from neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ) and migration of newly formed neuroblasts towards the damaged striatum where they differentiate to mature neurons. Whether it is the injury per se or the associated inflammation that gives rise to this endogenous neurogenic response is unknown. Here we showed that inflammation without corresponding neuronal loss caused by intrastriatal lipopolysaccharide (LPS) injection leads to striatal neurogenesis in rats comparable to that after a 30 min middle cerebral artery occlusion, as characterized by striatal DCX + neuroblast recruitment and mature NeuN +/BrdU + neuron formation. Using global gene expression analysis, changes in several factors that could potentially regulate striatal neurogenesis were identified in microglia sorted from SVZ and striatum of LPS-injected and stroke-subjected rats. Among the upregulated factors, one chemokine, CXCL13, was found to promote neuroblast migration from neonatal mouse SVZ explants in vitro. However, neuroblast migration to the striatum was not affected in constitutive CXCL13 receptor CXCR5^−/− mice subjected to stroke. Infarct volume and pro-inflammatory M1 microglia/macrophage density were increased in CXCR5^−/− mice, suggesting that microglia-derived CXCL13, acting through CXCR5, might be involved in neuroprotection following stroke. Our findings raise the possibility that the inflammation accompanying an ischemic insult is the major inducer of striatal neurogenesis after stroke.

Grafted human neural stem cells enhance several steps of endogenous neurogenesis and improve behavioral recovery after middle cerebral artery occlusion in rats

Oh no, we're creating  human brains in rats. Shades of Christine O’Donnell famously insisting that scientists were putting human brains into mice. 

Grafted human neural stem cells enhance several steps of endogenous neurogenesis and improve behavioral recovery after middle cerebral artery occlusion in rats

Abstract 

Neural stem/progenitor cells (NSPCs) in subventricular zone (SVZ) produce new striatal neurons during several months after stroke, which may contribute to recovery. Intracerebral grafts of NSPCs can exert beneficial effects after stroke through neuronal replacement, trophic actions, neuroprotection, and modulation of inflammation. Here we have explored whether human fetal striatum-derived NSPC-grafts influence striatal neurogenesis and promote recovery in stroke-damaged brain. T cell-deficient rats were subjected to 1 h middle cerebral artery occlusion (MCAO). Human fetal NSPCs or vehicle were implanted into ipsilateral striatum 48 h after MCAO, animals were assessed behaviorally, and perfused at 6 or 14 weeks. Grafted human NSPCs survived in all rats, and a subpopulation had differentiated to neuroblasts or mature neurons at 6 and 14 weeks. Numbers of proliferating cells in SVZ and new migrating neuroblasts and mature neurons were higher, and numbers of activated microglia/macrophages were lower in the ischemic striatum of NSPC-grafted compared to vehicle-injected group both at 6 and 14 weeks. A fraction of grafted NSPCs projected axons from striatum to globus pallidus. The NSPC-grafted rats showed improved functional recovery in stepping and cylinder tests from 6 and 12 weeks, respectively. Our data show, for the first time, that intrastriatal implants of human fetal NSPCs exert a long-term enhancement of several steps of striatal neurogensis after stroke. The grafts also suppress striatal inflammation and ameliorate neurological deficits. Our findings support the idea that combination of NSPC transplantation and stimulation of neurogenesis from endogenous NSPCs may become a valuable strategy for functional restoration after stroke.