NADPH oxidase 2 deletion enhances neurogenesis following traumatic brain injury

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2 Citations (Scopus)

Abstract

The NADPH oxidase (NOX) enzyme family is a major source of reactive oxygen species (ROS) and contributor to the secondary pathology underlying traumatic brain injury (TBI). However, little is known about how NOX-derived ROS influences the proliferation and cell-fate determination of neural stem/progenitor cells (NSCs/NPCs) following TBI. In the current study, we found that deletion of NOX2 (NOX2-KO) significantly decreases the population of radial glia-like NSCs and neuroblasts but maintains the population of non-radial Sox2 expressing stem cells under physiological (non-injury) conditions. Surprisingly, the brains of NOX2-KO mice demonstrated a robust increase in the number of neuroblasts during the first week after TBI, as compared to the wild-type group. This increase may result from an enhanced proliferation of NPCs in a lower ROS environment after brain injury, as further examination revealed a significant increase of dividing neuroblasts in both NOX2-KO and NOX inhibitor-treated mouse brain during the first week following TBI. Finally, 5-Bromo-2′-deoxyuridine (BrdU) lineage tracing demonstrated a significantly increased number of newborn neurons were present in the perilesional cortex of NOX2-KO mice at 5 weeks post TBI, indicating that deletion of NOX2 promotes long-term neurogenesis in the injured brain following TBI. Altogether, these findings suggest that targeting NOX through genetic deletion or inhibition enhances post-injury neurogenesis, which may be beneficial for recovery following TBI.

Original languageEnglish (US)
Pages (from-to)62-71
Number of pages10
JournalFree Radical Biology and Medicine
Volume123
DOIs
StatePublished - Aug 1 2018

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NADPH Oxidase
Neurogenesis
Brain
Reactive Oxygen Species
Stem Cells
Stem cells
Neural Stem Cells
Population Dynamics
Bromodeoxyuridine
Traumatic Brain Injury
Neuroglia
Brain Injuries
Cell Proliferation
Pathology
Neurons
Wounds and Injuries
Enzymes
Population
Recovery

Keywords

  • NADPH oxidase
  • NOX inhibitor
  • NOX2
  • Neurogenesis
  • Traumatic brain injury

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

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title = "NADPH oxidase 2 deletion enhances neurogenesis following traumatic brain injury",
abstract = "The NADPH oxidase (NOX) enzyme family is a major source of reactive oxygen species (ROS) and contributor to the secondary pathology underlying traumatic brain injury (TBI). However, little is known about how NOX-derived ROS influences the proliferation and cell-fate determination of neural stem/progenitor cells (NSCs/NPCs) following TBI. In the current study, we found that deletion of NOX2 (NOX2-KO) significantly decreases the population of radial glia-like NSCs and neuroblasts but maintains the population of non-radial Sox2 expressing stem cells under physiological (non-injury) conditions. Surprisingly, the brains of NOX2-KO mice demonstrated a robust increase in the number of neuroblasts during the first week after TBI, as compared to the wild-type group. This increase may result from an enhanced proliferation of NPCs in a lower ROS environment after brain injury, as further examination revealed a significant increase of dividing neuroblasts in both NOX2-KO and NOX inhibitor-treated mouse brain during the first week following TBI. Finally, 5-Bromo-2′-deoxyuridine (BrdU) lineage tracing demonstrated a significantly increased number of newborn neurons were present in the perilesional cortex of NOX2-KO mice at 5 weeks post TBI, indicating that deletion of NOX2 promotes long-term neurogenesis in the injured brain following TBI. Altogether, these findings suggest that targeting NOX through genetic deletion or inhibition enhances post-injury neurogenesis, which may be beneficial for recovery following TBI.",
keywords = "NADPH oxidase, NOX inhibitor, NOX2, Neurogenesis, Traumatic brain injury",
author = "Jing Wang and Ma, {Merry W.} and Dhandapani, {Krishnan Michael} and Brann, {Darrell W}",
year = "2018",
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doi = "10.1016/j.freeradbiomed.2018.05.069",
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T1 - NADPH oxidase 2 deletion enhances neurogenesis following traumatic brain injury

AU - Wang, Jing

AU - Ma, Merry W.

AU - Dhandapani, Krishnan Michael

AU - Brann, Darrell W

PY - 2018/8/1

Y1 - 2018/8/1

N2 - The NADPH oxidase (NOX) enzyme family is a major source of reactive oxygen species (ROS) and contributor to the secondary pathology underlying traumatic brain injury (TBI). However, little is known about how NOX-derived ROS influences the proliferation and cell-fate determination of neural stem/progenitor cells (NSCs/NPCs) following TBI. In the current study, we found that deletion of NOX2 (NOX2-KO) significantly decreases the population of radial glia-like NSCs and neuroblasts but maintains the population of non-radial Sox2 expressing stem cells under physiological (non-injury) conditions. Surprisingly, the brains of NOX2-KO mice demonstrated a robust increase in the number of neuroblasts during the first week after TBI, as compared to the wild-type group. This increase may result from an enhanced proliferation of NPCs in a lower ROS environment after brain injury, as further examination revealed a significant increase of dividing neuroblasts in both NOX2-KO and NOX inhibitor-treated mouse brain during the first week following TBI. Finally, 5-Bromo-2′-deoxyuridine (BrdU) lineage tracing demonstrated a significantly increased number of newborn neurons were present in the perilesional cortex of NOX2-KO mice at 5 weeks post TBI, indicating that deletion of NOX2 promotes long-term neurogenesis in the injured brain following TBI. Altogether, these findings suggest that targeting NOX through genetic deletion or inhibition enhances post-injury neurogenesis, which may be beneficial for recovery following TBI.

AB - The NADPH oxidase (NOX) enzyme family is a major source of reactive oxygen species (ROS) and contributor to the secondary pathology underlying traumatic brain injury (TBI). However, little is known about how NOX-derived ROS influences the proliferation and cell-fate determination of neural stem/progenitor cells (NSCs/NPCs) following TBI. In the current study, we found that deletion of NOX2 (NOX2-KO) significantly decreases the population of radial glia-like NSCs and neuroblasts but maintains the population of non-radial Sox2 expressing stem cells under physiological (non-injury) conditions. Surprisingly, the brains of NOX2-KO mice demonstrated a robust increase in the number of neuroblasts during the first week after TBI, as compared to the wild-type group. This increase may result from an enhanced proliferation of NPCs in a lower ROS environment after brain injury, as further examination revealed a significant increase of dividing neuroblasts in both NOX2-KO and NOX inhibitor-treated mouse brain during the first week following TBI. Finally, 5-Bromo-2′-deoxyuridine (BrdU) lineage tracing demonstrated a significantly increased number of newborn neurons were present in the perilesional cortex of NOX2-KO mice at 5 weeks post TBI, indicating that deletion of NOX2 promotes long-term neurogenesis in the injured brain following TBI. Altogether, these findings suggest that targeting NOX through genetic deletion or inhibition enhances post-injury neurogenesis, which may be beneficial for recovery following TBI.

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