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Adoptive transfer of immune subsets prior to MCAO does not exacerbate stroke outcome in splenectomized mice.

Wang J, Dotson AL, Murphy SJ, Offner H, Saugstad JA - J Syst Integr Neurosci (2015)

Bottom Line: The results demonstrate that CD4/CD8/CD11b treated mice had no significant effect on infarct volumes vs. vehicle-treated control mice after MCAO.However, there were significant alterations to the resident peripheral immune composition.These results suggest that there are regulatory factors resulting from splenectomy or other possible influences that inhibit peripheral immune cell contribution to neuroinflammation and thus contributing to differential effects of the spleen on stroke outcome in males and female mice.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR, USA.

ABSTRACT

The peripheral immune response contributes to neurologic impairment after stroke and the extent of initial damage is greater in males than females. We have previously shown that spleen cells directly contribute to ischemic damage in males, as splenectomy prior to experimental stroke eliminates the sex differences in infarct volume. This study aims to determine which specific subset of immune cells exert pathogenic effects when injected 24 hours before MCAO induction into splenectomized male and female WT mice. The results demonstrate that CD4/CD8/CD11b treated mice had no significant effect on infarct volumes vs. vehicle-treated control mice after MCAO. However, there were significant alterations to the resident peripheral immune composition. These results suggest that there are regulatory factors resulting from splenectomy or other possible influences that inhibit peripheral immune cell contribution to neuroinflammation and thus contributing to differential effects of the spleen on stroke outcome in males and female mice.

No MeSH data available.


Related in: MedlinePlus

Adoptive transfer of CD4+ or CD8+ T cells to splenectomized male or female mice does not exacerbate infarct volume induced by focal ischemiaMale and female mice were subject to splenectomy two weeks prior to transient MCAO (60 min). Mice were injected with CD4+ or CD8+ T cells 24 hours prior to MCAO. Brains were harvested 96 h after MCAO. (A) Infarct volumes measured as percentage of corrected contralateral structure for male mice injected with saline vehicle (n=10), 12 million CD4+ T cells (n=12), or 8 million CD8+ T cells (n=14) by intravenous transfer 24 h before MCAO. (B) Representative brain slices for male mice stained with TTC. Values represent mean numbers (± SEM) of splenectomized males per group analyzed using a one-way ANOVA. (C) Infarct volumes measured as percentage of corrected contralateral structure for female mice injected with saline vehicle (n=12), 12 million CD4+ T cells (n=11), or 8 million CD8+ T cells (n=11) by intravenous transfer 24 h before MCAO. (B) Representative brain slices for female mice stained with TTC. Values represent mean numbers (± SEM) of splenectomized females per group analyzed using a one-way ANOVA.
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Figure 1: Adoptive transfer of CD4+ or CD8+ T cells to splenectomized male or female mice does not exacerbate infarct volume induced by focal ischemiaMale and female mice were subject to splenectomy two weeks prior to transient MCAO (60 min). Mice were injected with CD4+ or CD8+ T cells 24 hours prior to MCAO. Brains were harvested 96 h after MCAO. (A) Infarct volumes measured as percentage of corrected contralateral structure for male mice injected with saline vehicle (n=10), 12 million CD4+ T cells (n=12), or 8 million CD8+ T cells (n=14) by intravenous transfer 24 h before MCAO. (B) Representative brain slices for male mice stained with TTC. Values represent mean numbers (± SEM) of splenectomized males per group analyzed using a one-way ANOVA. (C) Infarct volumes measured as percentage of corrected contralateral structure for female mice injected with saline vehicle (n=12), 12 million CD4+ T cells (n=11), or 8 million CD8+ T cells (n=11) by intravenous transfer 24 h before MCAO. (B) Representative brain slices for female mice stained with TTC. Values represent mean numbers (± SEM) of splenectomized females per group analyzed using a one-way ANOVA.

Mentions: We examined the effect of adoptive transfer of CD4+ and CD8+ T cells on infarct volume in splenectomized mice. Male and female C57BL/6J WT mice underwent splenectomy two weeks prior to focal cerebral ischemia induced by MCAO. 24 h before MCAO the splenectomized mice were intravenously given saline (no cells), or a spleen equivalent number of CD4+ T cells or CD8+ T cells (12x106 and 8x106, respectively). The mice were subject to 60 min MCAO, followed by 96 h reperfusion when brains were evaluated for infarct volume. The results show that adoptive transfer of 12 million CD4+ T cells (n = 12), or 8 million CD8+ T cells (n = 14) had no effect on infarct volume in male mice, relative to injection of saline (n = 10) (Figure 1A). Representative TTC stains of cerebral sections of male mice 96 h after MCAO show that localization of the ischemic lesion did not differ between splenectomized male mice receiving intravenous saline (Figure 1B, left column) vs. CD4+ or CD8+ T cells (Figure 1B, right columns) 24 h before MCAO. Similarly, the results show that adoptive transfer of 12 million CD4+ T cells (n = 12), or 8 million CD8+ T cells (n = 11) had no effect on infarct volume in female mice, relative to injection of saline (n = 11) (Figure 1C). Representative TTC stains of cerebral sections of female mice 96 h after MCAO show that localization of the ischemic lesion did not differ between splenectomized male mice receiving intravenous saline (Figure 1D, left column) vs. CD4+ or CD8+ T cells (Figure 1D, right columns) 24 h before MCAO. All values represent mean numbers (± SEM) of splenectomized mice per group analyzed using a one-way ANOVA.


Adoptive transfer of immune subsets prior to MCAO does not exacerbate stroke outcome in splenectomized mice.

Wang J, Dotson AL, Murphy SJ, Offner H, Saugstad JA - J Syst Integr Neurosci (2015)

Adoptive transfer of CD4+ or CD8+ T cells to splenectomized male or female mice does not exacerbate infarct volume induced by focal ischemiaMale and female mice were subject to splenectomy two weeks prior to transient MCAO (60 min). Mice were injected with CD4+ or CD8+ T cells 24 hours prior to MCAO. Brains were harvested 96 h after MCAO. (A) Infarct volumes measured as percentage of corrected contralateral structure for male mice injected with saline vehicle (n=10), 12 million CD4+ T cells (n=12), or 8 million CD8+ T cells (n=14) by intravenous transfer 24 h before MCAO. (B) Representative brain slices for male mice stained with TTC. Values represent mean numbers (± SEM) of splenectomized males per group analyzed using a one-way ANOVA. (C) Infarct volumes measured as percentage of corrected contralateral structure for female mice injected with saline vehicle (n=12), 12 million CD4+ T cells (n=11), or 8 million CD8+ T cells (n=11) by intravenous transfer 24 h before MCAO. (B) Representative brain slices for female mice stained with TTC. Values represent mean numbers (± SEM) of splenectomized females per group analyzed using a one-way ANOVA.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4664464&req=5

Figure 1: Adoptive transfer of CD4+ or CD8+ T cells to splenectomized male or female mice does not exacerbate infarct volume induced by focal ischemiaMale and female mice were subject to splenectomy two weeks prior to transient MCAO (60 min). Mice were injected with CD4+ or CD8+ T cells 24 hours prior to MCAO. Brains were harvested 96 h after MCAO. (A) Infarct volumes measured as percentage of corrected contralateral structure for male mice injected with saline vehicle (n=10), 12 million CD4+ T cells (n=12), or 8 million CD8+ T cells (n=14) by intravenous transfer 24 h before MCAO. (B) Representative brain slices for male mice stained with TTC. Values represent mean numbers (± SEM) of splenectomized males per group analyzed using a one-way ANOVA. (C) Infarct volumes measured as percentage of corrected contralateral structure for female mice injected with saline vehicle (n=12), 12 million CD4+ T cells (n=11), or 8 million CD8+ T cells (n=11) by intravenous transfer 24 h before MCAO. (B) Representative brain slices for female mice stained with TTC. Values represent mean numbers (± SEM) of splenectomized females per group analyzed using a one-way ANOVA.
Mentions: We examined the effect of adoptive transfer of CD4+ and CD8+ T cells on infarct volume in splenectomized mice. Male and female C57BL/6J WT mice underwent splenectomy two weeks prior to focal cerebral ischemia induced by MCAO. 24 h before MCAO the splenectomized mice were intravenously given saline (no cells), or a spleen equivalent number of CD4+ T cells or CD8+ T cells (12x106 and 8x106, respectively). The mice were subject to 60 min MCAO, followed by 96 h reperfusion when brains were evaluated for infarct volume. The results show that adoptive transfer of 12 million CD4+ T cells (n = 12), or 8 million CD8+ T cells (n = 14) had no effect on infarct volume in male mice, relative to injection of saline (n = 10) (Figure 1A). Representative TTC stains of cerebral sections of male mice 96 h after MCAO show that localization of the ischemic lesion did not differ between splenectomized male mice receiving intravenous saline (Figure 1B, left column) vs. CD4+ or CD8+ T cells (Figure 1B, right columns) 24 h before MCAO. Similarly, the results show that adoptive transfer of 12 million CD4+ T cells (n = 12), or 8 million CD8+ T cells (n = 11) had no effect on infarct volume in female mice, relative to injection of saline (n = 11) (Figure 1C). Representative TTC stains of cerebral sections of female mice 96 h after MCAO show that localization of the ischemic lesion did not differ between splenectomized male mice receiving intravenous saline (Figure 1D, left column) vs. CD4+ or CD8+ T cells (Figure 1D, right columns) 24 h before MCAO. All values represent mean numbers (± SEM) of splenectomized mice per group analyzed using a one-way ANOVA.

Bottom Line: The results demonstrate that CD4/CD8/CD11b treated mice had no significant effect on infarct volumes vs. vehicle-treated control mice after MCAO.However, there were significant alterations to the resident peripheral immune composition.These results suggest that there are regulatory factors resulting from splenectomy or other possible influences that inhibit peripheral immune cell contribution to neuroinflammation and thus contributing to differential effects of the spleen on stroke outcome in males and female mice.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR, USA.

ABSTRACT

The peripheral immune response contributes to neurologic impairment after stroke and the extent of initial damage is greater in males than females. We have previously shown that spleen cells directly contribute to ischemic damage in males, as splenectomy prior to experimental stroke eliminates the sex differences in infarct volume. This study aims to determine which specific subset of immune cells exert pathogenic effects when injected 24 hours before MCAO induction into splenectomized male and female WT mice. The results demonstrate that CD4/CD8/CD11b treated mice had no significant effect on infarct volumes vs. vehicle-treated control mice after MCAO. However, there were significant alterations to the resident peripheral immune composition. These results suggest that there are regulatory factors resulting from splenectomy or other possible influences that inhibit peripheral immune cell contribution to neuroinflammation and thus contributing to differential effects of the spleen on stroke outcome in males and female mice.

No MeSH data available.


Related in: MedlinePlus