Abstract
Perinatal hypoxia/ischemia (H/I) is the leading cause of neurologic injury resulting from birth complications. Recent advances in critical care have dramatically improved the survival rate of infants suffering this insult, but ∼50% of survivors will develop neurologic sequelae such as cerebral palsy, epilepsy or cognitive deficits. Here we demonstrate that tripotential neural stem/progenitor cells (NSPs) participate in the regenerative response to perinatal H/I as their numbers increase 100% by 3 d and that they alter their intrinsic properties to divide using expansive symmetrical cell divisions. We further show that production of new striatal neurons follows the expansion of NSPs. Increased proliferation within the NSP niche occurs at 2 d after perinatal H/I, and the proliferating cells express nestin. Of those stem-cell related genes that change, the membrane receptors Notch1, gp-130, and the epidermal growth factor receptor, as well as the downstream transcription factor Hes5, which stimulate NSP proliferation and regulate stem cellness are induced before NSP expansion. The mechanisms for the reactive expansion of the NSPs reported here reveal potential therapeutic targets that could be exploited to amplify this response, thus enabling endogenous precursors to restore a normal pattern of brain development after perinatal H/I.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4359-4369 |
| Number of pages | 11 |
| Journal | Journal of Neuroscience |
| Volume | 26 |
| Issue number | 16 |
| DOIs | |
| State | Published - Sep 7 2006 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
Keywords
- Cerebral palsy
- Neurogenesis
- Notch
- Regeneration
- Self-renewal
- Subventricular zone
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Neural stem/progenitor cells participate in the regenerative response to perinatal hypoxia/ischemia. / Felling, Ryan J.; Snyder, Matthew J.; Romanko, Michael J.; Rothstein, Raymond P.; Ziegler, Amber N.; Yang, Zhengang; Givogri, Maria I.; Bongarzone, Ernesto R.; Levison, Steven W.
In: Journal of Neuroscience, Vol. 26, No. 16, 07.09.2006, p. 4359-4369.Research output: Contribution to journal › Article
TY - JOUR
T1 - Neural stem/progenitor cells participate in the regenerative response to perinatal hypoxia/ischemia
AU - Felling, Ryan J.
AU - Snyder, Matthew J.
AU - Romanko, Michael J.
AU - Rothstein, Raymond P.
AU - Ziegler, Amber N.
AU - Yang, Zhengang
AU - Givogri, Maria I.
AU - Bongarzone, Ernesto R.
AU - Levison, Steven W.
PY - 2006/9/7
Y1 - 2006/9/7
N2 - Perinatal hypoxia/ischemia (H/I) is the leading cause of neurologic injury resulting from birth complications. Recent advances in critical care have dramatically improved the survival rate of infants suffering this insult, but ∼50% of survivors will develop neurologic sequelae such as cerebral palsy, epilepsy or cognitive deficits. Here we demonstrate that tripotential neural stem/progenitor cells (NSPs) participate in the regenerative response to perinatal H/I as their numbers increase 100% by 3 d and that they alter their intrinsic properties to divide using expansive symmetrical cell divisions. We further show that production of new striatal neurons follows the expansion of NSPs. Increased proliferation within the NSP niche occurs at 2 d after perinatal H/I, and the proliferating cells express nestin. Of those stem-cell related genes that change, the membrane receptors Notch1, gp-130, and the epidermal growth factor receptor, as well as the downstream transcription factor Hes5, which stimulate NSP proliferation and regulate stem cellness are induced before NSP expansion. The mechanisms for the reactive expansion of the NSPs reported here reveal potential therapeutic targets that could be exploited to amplify this response, thus enabling endogenous precursors to restore a normal pattern of brain development after perinatal H/I.
AB - Perinatal hypoxia/ischemia (H/I) is the leading cause of neurologic injury resulting from birth complications. Recent advances in critical care have dramatically improved the survival rate of infants suffering this insult, but ∼50% of survivors will develop neurologic sequelae such as cerebral palsy, epilepsy or cognitive deficits. Here we demonstrate that tripotential neural stem/progenitor cells (NSPs) participate in the regenerative response to perinatal H/I as their numbers increase 100% by 3 d and that they alter their intrinsic properties to divide using expansive symmetrical cell divisions. We further show that production of new striatal neurons follows the expansion of NSPs. Increased proliferation within the NSP niche occurs at 2 d after perinatal H/I, and the proliferating cells express nestin. Of those stem-cell related genes that change, the membrane receptors Notch1, gp-130, and the epidermal growth factor receptor, as well as the downstream transcription factor Hes5, which stimulate NSP proliferation and regulate stem cellness are induced before NSP expansion. The mechanisms for the reactive expansion of the NSPs reported here reveal potential therapeutic targets that could be exploited to amplify this response, thus enabling endogenous precursors to restore a normal pattern of brain development after perinatal H/I.
KW - Cerebral palsy
KW - Neurogenesis
KW - Notch
KW - Regeneration
KW - Self-renewal
KW - Subventricular zone
UR - http://www.scopus.com/inward/record.url?scp=33646439569&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646439569&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1898-05.2006
DO - 10.1523/JNEUROSCI.1898-05.2006
M3 - Article
C2 - 16624956
AN - SCOPUS:33646439569
VL - 26
SP - 4359
EP - 4369
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 16
ER -