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Reparative effects of neural stem cells in neonatal rats with hypoxic-ischemic injury are not influenced by host sex.

Ashwal S, Ghosh N, Turenius CI, Dulcich M, Denham CM, Tone B, Hartman R, Snyder EY, Obenaus A - Pediatr. Res. (2014)

Bottom Line: We monitored HII evolution (by magnetic resonance imaging, histopathology, behavioral testing) and hNSC fate (migration, replication, viability).Superparamagnetic iron oxide labeling did not influence HII evolution.Our results suggest that hNSC treatment (including using hNSCs that are prelabeled with iron to allow tracking in real time by magnetic resonance imaging) would be equally safe and effective for male and female human newborns with mild-to-moderate HII.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California.

ABSTRACT

Background: Gender is increasingly recognized as an important influence on brain development, disease susceptibility, and response to pharmacologic/rehabilitative treatments. In regenerative medicine, it remains entirely unknown whether there is an interaction between transplanted stem cells and host gender that might bias efficacy and safety in some patients but not others.

Methods: We examined the role of recipient gender in a neonatal rat hypoxic-ischemic injury (HII) model, treated with female human neuronal stem cells (hNSCs), labeled with superparamagnetic iron oxide particles implanted into the contralateral cerebral ventricle. We monitored HII evolution (by magnetic resonance imaging, histopathology, behavioral testing) and hNSC fate (migration, replication, viability).

Results: Recipient gender after implantation did not influence the volume or location of ischemic injury (1, 30, or 90 d) or behavior (90 d). Superparamagnetic iron oxide labeling did not influence HII evolution. Implantation had its greatest benefit on mild/moderate injuries, which remained stable rather than increasing as in severe HII as is the natural history for such lesions.

Conclusion: Our results suggest that hNSC treatment (including using hNSCs that are prelabeled with iron to allow tracking in real time by magnetic resonance imaging) would be equally safe and effective for male and female human newborns with mild-to-moderate HII.

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Related in: MedlinePlus

Behavioral testing demonstrated learning and exploratory deficits based on injury severity but not on gender or labeling statusA) Behavioral testing based on lesion severity revealed that those animals with mild injury had improved spatial memory compared to moderate or severely injured animals (p<0.007). B) Similarly, animals with severe injury spent more time exploring an open field than their mild and moderate injury counterparts (p<0.04). (● mild, ○ moderate, ■ severe)
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Figure 6: Behavioral testing demonstrated learning and exploratory deficits based on injury severity but not on gender or labeling statusA) Behavioral testing based on lesion severity revealed that those animals with mild injury had improved spatial memory compared to moderate or severely injured animals (p<0.007). B) Similarly, animals with severe injury spent more time exploring an open field than their mild and moderate injury counterparts (p<0.04). (● mild, ○ moderate, ■ severe)

Mentions: Behavioral assessment just prior to the final 90d time point found no significant differences based on gender or hNSC labeling (Figure 6). Neither gender nor labeling had any effects on anxiety-like behaviors in the elevated zero maze, although females spent more time in the enclosed arms, suggesting some increased anxiety (p<0.02; data not shown).


Reparative effects of neural stem cells in neonatal rats with hypoxic-ischemic injury are not influenced by host sex.

Ashwal S, Ghosh N, Turenius CI, Dulcich M, Denham CM, Tone B, Hartman R, Snyder EY, Obenaus A - Pediatr. Res. (2014)

Behavioral testing demonstrated learning and exploratory deficits based on injury severity but not on gender or labeling statusA) Behavioral testing based on lesion severity revealed that those animals with mild injury had improved spatial memory compared to moderate or severely injured animals (p<0.007). B) Similarly, animals with severe injury spent more time exploring an open field than their mild and moderate injury counterparts (p<0.04). (● mild, ○ moderate, ■ severe)
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4404035&req=5

Figure 6: Behavioral testing demonstrated learning and exploratory deficits based on injury severity but not on gender or labeling statusA) Behavioral testing based on lesion severity revealed that those animals with mild injury had improved spatial memory compared to moderate or severely injured animals (p<0.007). B) Similarly, animals with severe injury spent more time exploring an open field than their mild and moderate injury counterparts (p<0.04). (● mild, ○ moderate, ■ severe)
Mentions: Behavioral assessment just prior to the final 90d time point found no significant differences based on gender or hNSC labeling (Figure 6). Neither gender nor labeling had any effects on anxiety-like behaviors in the elevated zero maze, although females spent more time in the enclosed arms, suggesting some increased anxiety (p<0.02; data not shown).

Bottom Line: We monitored HII evolution (by magnetic resonance imaging, histopathology, behavioral testing) and hNSC fate (migration, replication, viability).Superparamagnetic iron oxide labeling did not influence HII evolution.Our results suggest that hNSC treatment (including using hNSCs that are prelabeled with iron to allow tracking in real time by magnetic resonance imaging) would be equally safe and effective for male and female human newborns with mild-to-moderate HII.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California.

ABSTRACT

Background: Gender is increasingly recognized as an important influence on brain development, disease susceptibility, and response to pharmacologic/rehabilitative treatments. In regenerative medicine, it remains entirely unknown whether there is an interaction between transplanted stem cells and host gender that might bias efficacy and safety in some patients but not others.

Methods: We examined the role of recipient gender in a neonatal rat hypoxic-ischemic injury (HII) model, treated with female human neuronal stem cells (hNSCs), labeled with superparamagnetic iron oxide particles implanted into the contralateral cerebral ventricle. We monitored HII evolution (by magnetic resonance imaging, histopathology, behavioral testing) and hNSC fate (migration, replication, viability).

Results: Recipient gender after implantation did not influence the volume or location of ischemic injury (1, 30, or 90 d) or behavior (90 d). Superparamagnetic iron oxide labeling did not influence HII evolution. Implantation had its greatest benefit on mild/moderate injuries, which remained stable rather than increasing as in severe HII as is the natural history for such lesions.

Conclusion: Our results suggest that hNSC treatment (including using hNSCs that are prelabeled with iron to allow tracking in real time by magnetic resonance imaging) would be equally safe and effective for male and female human newborns with mild-to-moderate HII.

Show MeSH
Related in: MedlinePlus