Endothelial Nitric Oxide Synthase Regulates Brain-Derived Neurotrophic Factor Expression and Neurogenesis after Stroke in Mice
Jieli Chen,Alex Zacharek,Chunling Zhang,Hao Jiang,Yi Li,Cynthia Roberts,Mei Lu,Alissa Kapke,Michael Chopp +8 more
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TLDR
Data indicate that eNOS is not only a downstream mediator for VEGF and angiogenesis but also regulates BDNF expression in the ischemic brain and influences progenitor cell proliferation, neuronal migration, and neurite outgrowth and affects functional recovery after stroke.Abstract:
Here, we investigate the effects of endothelial nitric oxide synthase (eNOS) on angiogenesis, neurogenesis, neurotrophic factor expression, and neurological functional outcome after stroke. Wild-type and eNOS knock-out (eNOS-/-) mice were subjected to permanent occlusion of the right middle cerebral artery. eNOS-/- mice exhibited more severe neurological functional deficit after stroke than wild-type mice. Decreased subventricular zone (SVZ) progenitor cell proliferation and migration, measured using bromodeoxyuridine, Ki-67, nestin, and doublecortin immunostaining in the ischemic brain, and decreased angiogenesis, as demonstrated by reduced endothelial cell proliferation, vessel perimeter, and vascular density in the ischemic border, were evident in eNOS-/- mice compared with wild-type mice. eNOS-deficient mice also exhibited a reduced response to vascular endothelial growth factor (VEGF)-induced angiogenesis in a corneal assay. ELISAs showed that eNOS-/- mice have decreased brain-derived neurotrophic factor (BDNF) expression but not VEGF and basic fibroblast growth factor in the ischemic brain compared with wild-type mice. In addition, cultured SVZ neurosphere formation, proliferation, telomerase activity, and neurite outgrowth but not cell viability from eNOS-/- mice were significantly reduced compared with wild-type mice. BDNF treatment of SVZ cells derived from eNOS-/- mice restored the decreased neurosphere formation, proliferation, neurite outgrowth, and telomerase activity in cultured eNOS(-/-) SVZ neurospheres. SVZ explant cell migration also was significantly decreased in eNOS-/- mice compared with wild-type mice. These data indicate that eNOS is not only a downstream mediator for VEGF and angiogenesis but also regulates BDNF expression in the ischemic brain and influences progenitor cell proliferation, neuronal migration, and neurite outgrowth and affects functional recovery after stroke.read more
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Concepts of neural nitric oxide‐mediated transmission
TL;DR: Viewed from a mechanistic perspective, NO conforms to many of the rules governing more conventional neurotransmission, particularly of the metabotropic type, but stands out as being more economical and versatile, attributes that presumably account for its spectacular evolutionary success.
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Subventricular Zone-Derived Neuroblasts Migrate and Differentiate into Mature Neurons in the Post-Stroke Adult Striatum
Toru Yamashita,Mikiko Ninomiya,Mikiko Ninomiya,Pilar Hernández Acosta,José Manuel García-Verdugo,Takehiko Sunabori,Masanori Sakaguchi,Kazuhide Adachi,Takuro Kojima,Yuki Hirota,Takeshi Kawase,Nobuo Araki,Koji Abe,Hideyuki Okano,Kazunobu Sawamoto +14 more
TL;DR: Evidence is reported that, after a stroke, subventricular zone GFAP-expressing cells are capable of producing new neurons outside the olfactory bulbs, and long-term tracing of the green fluorescent-labeled cells revealed that the SVZ-derived neuroblasts differentiated into mature neurons in the striatum, in which they expressed neuronal-specific nuclear protein and formed synapses with neighboring striatal cells.
Journal ArticleDOI
Acute ischemic stroke: overview of major experimental rodent models, pathophysiology, and therapy of focal cerebral ischemia.
Aysan Durukan,Turgut Tatlisumak +1 more
TL;DR: Various rodent animal models, pathogenic mechanisms, and promising therapeutic approaches of ischemic stroke are focused on.
Journal ArticleDOI
Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic
TL;DR: The molecular pathways activated by these therapies, which induce remodelling of the injured brain via angiogenesis, neurogenesis, and axonal and dendritic plasticity, are discussed, may help with translation of restorative therapy from the laboratory to the clinic.
Journal ArticleDOI
Blood-brain barrier dysfunction and recovery after ischemic stroke.
Xiaoyan Jiang,Xiaoyan Jiang,Anuska V. Andjelkovic,Ling Zhu,Tuo Yang,Michael V. L. Bennett,Michael V. L. Bennett,Jun Chen,Jun Chen,Richard F. Keep,Yejie Shi +10 more
TL;DR: With the development of novel research tools, future research on theBBB is likely to reveal promising potential therapeutic targets for protecting the BBB and improving patient outcome after ischemic stroke.
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