Protective and regenerative response endogenously induced in the ischemic brain

2001 ◽  
Vol 79 (3) ◽  
pp. 262-265 ◽  
Author(s):  
Kazuo Kitagawa ◽  
Masayasu Matsumoto ◽  
Masatsugu Hori
Keyword(s):  
Dentate Gyrus ◽  
Progenitor Cells ◽  
Ischemic Tolerance ◽  
Ischemic Insult ◽  
Functional Deficits ◽  
Reactive Synaptogenesis ◽  
Injured Brain ◽  
New Strategy ◽  
Shock Proteins ◽  
Protective Proteins

Neuronal cells are highly vulnerable to ischemic insult. Because adult neurons are highly differentiated and cannot self-propagate, loss of neurons often results in functional deficits in mammalian brains. However, it has recently been shown that neurons and neuronal circuits exhibit protective and regenerative responses in a rodent model of experimental ischemia. At first, neurons respond by producing several protective proteins such as heat shock proteins (HSPs) after sublethal ischemia and then acquire tolerance against a subsequent ischemic insult (ischemic tolerance). Once neurons suffer irreversible injury, two repair processes, neurogenesis and synaptogenesis, are endogenously induced. Neuronal stem and (or) progenitor cells can proliferate in two brain areas in adult animals: the subventricular zone and the subgranular zone in the dentate gyrus. After ischemic insult, these stem (progenitor) cells proliferate and differentiate into neurons in the dentate gyrus of the hippocampus. Reactive synaptogenesis has been also observed in the injured brain following a period of long-term infarction, but it is unclear if it can compensate for disconnected circuits. Understanding the molecular mechanism underlying these protective and regenerative responses will be important in developing a new strategy for aimed at the augmentation of resistance against ischemic insult and the replacement of injured neurons and neuronal circuits.Key words: ischemic tolerance, neurogenesis, synaptogenesis.

scholarly journals Sevoflurane-Induced Neuroapoptosis in Rat Dentate Gyrus Is Activated by Autophagy Through NF-κB Signaling on the Late-Stage Progenitor Granule Cells

2020 ◽  
Vol 14 ◽  
Author(s):  
Dongyi Tong ◽  
Zhongliang Ma ◽  
Peng Su ◽  
Shuai Wang ◽  
Ying Xu ◽  
...  
Keyword(s):  
Western Blot ◽  
Dentate Gyrus ◽  
Progenitor Cells ◽  
Cognitive Deficits ◽  
Late Stage ◽  
Granule Cells ◽  
Female Rats ◽  
Short Term ◽  
Functional Deficits ◽  
Cognitive Deficiency

ObjectiveThe mechanisms by which exposure of the late-stage progenitor cells to the anesthesia sevoflurane alters their differentiation are not known. We seek to query whether the effects of sevoflurane on late-stage progenitor cells might be regulated by apoptosis and/or autophagy.MethodsTo address the short-term impact of sevoflurane exposure on granule cell differentiation, we used 5-bromo-2-deoxyuridine (BrdU) to identify the labeled late-stage progenitor granule cells. Male or female rats were exposed to 3% sevoflurane for 4 h when the labeled granule cells were 2 weeks old. Differentiation of the BrdU-labeled granule cells was quantified 4 and 7 days after exposure by double immunofluorescence. The expression of apoptosis and autophagy in hippocampal dentate gyrus (DG) was determined by western blot and immunofluorescence. Western blot for the expression of NF-κB was used to evaluate the mechanism. Morris water maze (MWM) test was performed to detect cognitive function in the rats on postnatal 28–33 days.ResultsExposure to sevoflurane decreased the differentiation of the BrdU-labeled late-stage progenitor granule cells, but increased the expression of caspase-3, autophagy, and phosphorylated-P65 in the hippocampus of juvenile rats and resulted in cognitive deficiency. These damaging effects of sevoflurane could be mitigated by inhibitors of autophagy, apoptosis, and NF-κB. The increased apoptosis could be alleviated by pretreatment with the autophagy inhibitor 3-MA, and the increased autophagy and apoptosis could be reduced by pretreatment with NF-κB inhibitor BAY 11-7085.ConclusionThese findings suggest that a single, prolonged sevoflurane exposure could impair the differentiation of late-stage progenitor granule cells in hippocampal DG and cause cognitive deficits possibly via apoptosis activated by autophagy through NF-κB signaling. Our results do not preclude the possibility that the affected differentiation and functional deficits may be caused by depletion of the progenitors pool.

Early proliferative response of radial glia-like progenitor cells in the dentate gyrus following focal ischemia

2005 ◽  
Vol 32 (S 4) ◽  
Author(s):  
A Kunze ◽  
S Grass ◽  
O.W Witte ◽  
G Kempermann ◽  
C Redecker
Keyword(s):  
Dentate Gyrus ◽  
Progenitor Cells ◽  
Proliferative Response ◽  
Radial Glia ◽  
Focal Ischemia

scholarly journals Liver X receptor β regulates the development of the dentate gyrus and autistic-like behavior in the mouse

2018 ◽  
Vol 115 (12) ◽  
pp. E2725-E2733 ◽  
Author(s):  
Yulong Cai ◽  
Xiaotong Tang ◽  
Xi Chen ◽  
Xin Li ◽  
Ying Wang ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Liver X Receptor ◽  
Self Renewal ◽  
Spectrum Disorders ◽  
Deficient Mice

The dentate gyrus (DG) of the hippocampus is a laminated brain region in which neurogenesis begins during early embryonic development and continues until adulthood. Recent studies have implicated that defects in the neurogenesis of the DG seem to be involved in the genesis of autism spectrum disorders (ASD)-like behaviors. Liver X receptor β (LXRβ) has recently emerged as an important transcription factor involved in the development of laminated CNS structures, but little is known about its role in the development of the DG. Here, we show that deletion of the LXRβ in mice causes hypoplasia in the DG, including abnormalities in the formation of progenitor cells and granule cell differentiation. We also found that expression of Notch1, a central mediator of progenitor cell self-renewal, is reduced in LXRβ-null mice. In addition, LXRβ deletion in mice results in autistic-like behaviors, including abnormal social interaction and repetitive behavior. These data reveal a central role for LXRβ in orchestrating the timely differentiation of neural progenitor cells within the DG, thereby providing a likely explanation for its association with the genesis of autism-related behaviors in LXRβ-deficient mice.

scholarly journals Cerebrovascular Hemodynamics and Ischemic Tolerance: Lipopolysaccharide-Induced Resistance to Focal Cerebral Ischemia is not Due to Changes in Severity of the Initial Ischemic Insult, but is Associated with Preservation of Microvascular Perfusion

1999 ◽  
Vol 19 (6) ◽  
pp. 616-623 ◽  
Author(s):  
Deborah A. Dawson ◽  
Kazuhide Furuya ◽  
Jun Gotoh ◽  
Yasuaki Nakao ◽  
John M. Hallenbeck
Keyword(s):  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Ischemic Injury ◽  
Ischemic Tolerance ◽  
Microvascular Perfusion ◽  
Saline Control ◽  
Ischemic Insult ◽  
Mca Occlusion ◽  
Induced Tolerance ◽  
Tissue Sparing

Lipopolysaccharide (LPS), administered 72 hours before middle cerebral artery (MCA) occlusion, confers significant protection against ischemic injury. For example, in the present study, LPS (0.9 mg/kg intravenously) induced a 31% reduction in infarct volume (compared with saline control) assessed 24 hours after permanent MCA occlusion. To determine whether LPS induces true tolerance to ischemia, or merely attenuates initial ischemic severity by augmenting collateral blood flow, local CBF was measured autoradiographically 15 minutes after MCA occlusion. Local CBF did not differ significantly between LPS- and saline-pretreated rats (e.g., 34 ± 10 and 29 ± 15 mL·100 g−1·min−1 for saline and LPS pretreatment in a representative region of ischemic cortex), indicating that the neuroprotective action of LPS is not attributable to an immediate reduction in the degree of ischemia induced by MCA occlusion, and that LPS does indeed induce a state of ischemic tolerance. In contrast to the similarity of the initial ischemic insult between tolerant (LPS-pretreated) and nontolerant (saline-pretreated) rats, microvascular perfusion assessed either 4 hours or 24 hours after MCA occlusion was preserved at significantly higher levels in the LPS-pretreated rats than in controls. Furthermore, the regions of preserved perfusion in tolerant animals were associated with regions of tissue sparing. These results suggest that LPS-induced tolerance to focal ischemia is at least partly dependent on the active maintenance of microvascular patency and hence the prevention of secondary ischemic injury.

A new strategy to improve the liver engraftment efficiency of transplanted human biliary tree stem/progenitor cells: cell coating with hyaluronic acid

2017 ◽  
Vol 66 (1) ◽  
pp. S42
Author(s):  
L. Nevi ◽  
G. Carpino ◽  
V. Cardinale ◽  
D. Costantini ◽  
S.D. Matteo ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Progenitor Cells ◽  
Biliary Tree ◽  
New Strategy ◽  
Cell Coating ◽  
Tree Stem

Comparative analyses of synaptic densities during reactive synaptogenesis in the rat dentate gyrus

2004 ◽  
Vol 996 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Diano F Marrone ◽  
Janelle C LeBoutillier ◽  
Ted L Petit
Keyword(s):  
Dentate Gyrus ◽  
Comparative Analyses ◽  
Reactive Synaptogenesis

scholarly journals Specification and maintenance of oligodendrocyte precursor cells from neural progenitor cells: involvement of microRNA-7a

2012 ◽  
Vol 23 (15) ◽  
pp. 2867-2877 ◽  
Author(s):  
Xianghui Zhao ◽  
Jiang Wu ◽  
Minhua Zheng ◽  
Fang Gao ◽  
Gong Ju
Keyword(s):  
Progenitor Cells ◽  
Cell Fate ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Precursor Cells ◽  
Specific Gene ◽  
Oligodendrocyte Precursor Cells ◽  
Embryonic Mouse ◽  
New Strategy ◽  
Oligodendrocyte Precursor

The generation of myelinating cells from multipotential neural stem cells in the CNS requires the initiation of specific gene expression programs in oligodendrocytes (OLs). We reasoned that microRNAs (miRNAs) could play an important role in this process by regulating genes crucial for OL development. Here we identified miR-7a as one of the highly enriched miRNAs in oligodendrocyte precursor cells (OPCs), overexpression of which in either neural progenitor cells (NPCs) or embryonic mouse cortex promoted the generation of OL lineage cells. Blocking the function of miR-7a in differentiating NPCs led to a reduction in OL number and an expansion of neuronal populations simultaneously. We also found that overexpression of this miRNA in purified OPC cultures promoted cell proliferation and inhibited further maturation. In addition, miR-7a might exert the effects just mentioned partially by directly repressing proneuronal differentiation factors including Pax6 and NeuroD4, or proOL genes involved in oligodendrocyte maturation. These results suggest that miRNA pathway is essential in determining cell fate commitment for OLs and thus providing a new strategy for modulating this process in OL loss diseases.

scholarly journals Impaired survival of neural progenitor cells in dentate gyrus of adult mice lacking FMRP

Hippocampus ◽  
2011 ◽  
Vol 22 (6) ◽  
pp. 1220-1224 ◽  
Author(s):  
Orly Lazarov ◽  
Michael P. Demars ◽  
Kai Da Tommy Zhao ◽  
Haroon M. Ali ◽  
Vanessa Grauzas ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Adult Mice
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