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Therapeutic effects of intravenous administration of bone marrow stromal cells on sevoflurane-induced neuronal apoptosis and neuroinflammation in neonatal rats.

Sun Z, Satomoto M, Makita K - Korean J Anesthesiol (2015)

Bottom Line: BMSC treatment did not suppress apoptosis induced by sevoflurane exposure (compared with the vehicle group).BMSC group).Intravenous administration of BMSCs reduces neuroinflammation, but does not attenuate apoptosis induced by sevoflurane exposure.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

ABSTRACT

Background: Sevoflurane exposure during the early postnatal period causes neuroinflammation and neuronal apoptosis in rodents. Bone marrow stromal cells (BMSCs) have been shown to protect and repair the damaged central nervous system, for example in ischemic stroke models. In this study, we investigated whether intravenous administration of BMSCs ameliorated neurodegeneration, induced by sevoflurane exposure, in neonatal rats.

Methods: Sprague-Dawley rat pups (postnatal day 7) were exposed to 2% sevoflurane for 6 h (vehicle group, n = 7). BMSCs were administered 30 min after induction of sevoflurane anesthesia (BMSCs group, n = 7). The pups were exposed to carrier gas only, as a negative control (mock anesthesia group, n = 4). We assessed the therapeutic effects of BMSC treatment by measuring expression of the pro-inflammatory cytokine interleukin-6 (IL-6), and levels of cleaved caspase-3, in brain tissues immediately following sevoflurane anesthesia.

Results: Analysis of the cleaved caspase-3 bands revealed that levels of activated caspase-3 were elevated in the vehicle group compared with the mock anesthesia group, indicating that a single exposure to sevoflurane at subclinical concentrations can precipitate neuronal apoptosis. BMSC treatment did not suppress apoptosis induced by sevoflurane exposure (compared with the vehicle group). The vehicle group had higher proinflammatory cytokine IL-6 protein levels compared with the mock anesthesia group, indicating that sevoflurane exposure induces IL-6 expression. BMSC treatment suppressed sevoflurane-induced increases in IL-6 expression, indicating that these cells can inhibit the neuroinflammation induced by sevoflurane exposure (vehicle group vs. BMSC group).

Conclusions: Intravenous administration of BMSCs reduces neuroinflammation, but does not attenuate apoptosis induced by sevoflurane exposure.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemistry for activated caspase-3 following 6 h of sevoflurane exposure. Immunohistochemistry was performed on coronal sections (bregma -1.94 mm) as described in Zhou et al. [25]. Black arrows represent caspase-3-positive cells, indicating apoptosis. (A) Activated caspase-3 in the retrosplenial cortex of the mock anesthesia group. (B) Activated caspase-3 in the retrosplenial cortex of the vehicle group. (C) Activated caspase-3 in the retrosplenial cortex of the BMSC treatment group. Scale bars: 100 µm; ×10 magnification, BMSC: bone marrow stromal cell.
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Figure 2: Immunohistochemistry for activated caspase-3 following 6 h of sevoflurane exposure. Immunohistochemistry was performed on coronal sections (bregma -1.94 mm) as described in Zhou et al. [25]. Black arrows represent caspase-3-positive cells, indicating apoptosis. (A) Activated caspase-3 in the retrosplenial cortex of the mock anesthesia group. (B) Activated caspase-3 in the retrosplenial cortex of the vehicle group. (C) Activated caspase-3 in the retrosplenial cortex of the BMSC treatment group. Scale bars: 100 µm; ×10 magnification, BMSC: bone marrow stromal cell.

Mentions: Immediately following the 6 h period of exposure to sevoflurane, the BMSC and vehicle treatment groups were assessed for proinflammatory cytokine IL-6, and activated (cleaved) caspase-3 levels, by western blotting. Analysis of the cleaved caspase-3 bands revealed that levels of activated caspase-3 were elevated in the vehicle group compared with the mock anesthesia group (P < 0.05), indicating that a single exposure to sevoflurane at subclinical concentrations can induce neuronal apoptosis. BMSC treatment did not suppress apoptosis induced by sevoflurane exposure (compared with the vehicle group, P < 0.05) (Fig. 1A). The vehicle group had higher proinflammatory cytokine IL-6 protein levels compared with the mock anesthesia group (P < 0.05), indicating that sevoflurane exposure induces IL-6 expression. BMSC treatment suppressed this sevoflurane-induced increase in IL-6 expression, indicating that these cells can inhibit neuroinflammation induced by sevoflurane exposure (vehicle group vs. BMSC group, P < 0.05) (Fig. 1B). Immunostaining for cleaved caspase-3 confirmed that there was no significant difference in cleaved caspase-3 levels between the BMSC and vehicle groups (Fig. 2). The number of caspase-3-positive cells was not significantly reduced by BMSC treatment.


Therapeutic effects of intravenous administration of bone marrow stromal cells on sevoflurane-induced neuronal apoptosis and neuroinflammation in neonatal rats.

Sun Z, Satomoto M, Makita K - Korean J Anesthesiol (2015)

Immunohistochemistry for activated caspase-3 following 6 h of sevoflurane exposure. Immunohistochemistry was performed on coronal sections (bregma -1.94 mm) as described in Zhou et al. [25]. Black arrows represent caspase-3-positive cells, indicating apoptosis. (A) Activated caspase-3 in the retrosplenial cortex of the mock anesthesia group. (B) Activated caspase-3 in the retrosplenial cortex of the vehicle group. (C) Activated caspase-3 in the retrosplenial cortex of the BMSC treatment group. Scale bars: 100 µm; ×10 magnification, BMSC: bone marrow stromal cell.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524940&req=5

Figure 2: Immunohistochemistry for activated caspase-3 following 6 h of sevoflurane exposure. Immunohistochemistry was performed on coronal sections (bregma -1.94 mm) as described in Zhou et al. [25]. Black arrows represent caspase-3-positive cells, indicating apoptosis. (A) Activated caspase-3 in the retrosplenial cortex of the mock anesthesia group. (B) Activated caspase-3 in the retrosplenial cortex of the vehicle group. (C) Activated caspase-3 in the retrosplenial cortex of the BMSC treatment group. Scale bars: 100 µm; ×10 magnification, BMSC: bone marrow stromal cell.
Mentions: Immediately following the 6 h period of exposure to sevoflurane, the BMSC and vehicle treatment groups were assessed for proinflammatory cytokine IL-6, and activated (cleaved) caspase-3 levels, by western blotting. Analysis of the cleaved caspase-3 bands revealed that levels of activated caspase-3 were elevated in the vehicle group compared with the mock anesthesia group (P < 0.05), indicating that a single exposure to sevoflurane at subclinical concentrations can induce neuronal apoptosis. BMSC treatment did not suppress apoptosis induced by sevoflurane exposure (compared with the vehicle group, P < 0.05) (Fig. 1A). The vehicle group had higher proinflammatory cytokine IL-6 protein levels compared with the mock anesthesia group (P < 0.05), indicating that sevoflurane exposure induces IL-6 expression. BMSC treatment suppressed this sevoflurane-induced increase in IL-6 expression, indicating that these cells can inhibit neuroinflammation induced by sevoflurane exposure (vehicle group vs. BMSC group, P < 0.05) (Fig. 1B). Immunostaining for cleaved caspase-3 confirmed that there was no significant difference in cleaved caspase-3 levels between the BMSC and vehicle groups (Fig. 2). The number of caspase-3-positive cells was not significantly reduced by BMSC treatment.

Bottom Line: BMSC treatment did not suppress apoptosis induced by sevoflurane exposure (compared with the vehicle group).BMSC group).Intravenous administration of BMSCs reduces neuroinflammation, but does not attenuate apoptosis induced by sevoflurane exposure.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

ABSTRACT

Background: Sevoflurane exposure during the early postnatal period causes neuroinflammation and neuronal apoptosis in rodents. Bone marrow stromal cells (BMSCs) have been shown to protect and repair the damaged central nervous system, for example in ischemic stroke models. In this study, we investigated whether intravenous administration of BMSCs ameliorated neurodegeneration, induced by sevoflurane exposure, in neonatal rats.

Methods: Sprague-Dawley rat pups (postnatal day 7) were exposed to 2% sevoflurane for 6 h (vehicle group, n = 7). BMSCs were administered 30 min after induction of sevoflurane anesthesia (BMSCs group, n = 7). The pups were exposed to carrier gas only, as a negative control (mock anesthesia group, n = 4). We assessed the therapeutic effects of BMSC treatment by measuring expression of the pro-inflammatory cytokine interleukin-6 (IL-6), and levels of cleaved caspase-3, in brain tissues immediately following sevoflurane anesthesia.

Results: Analysis of the cleaved caspase-3 bands revealed that levels of activated caspase-3 were elevated in the vehicle group compared with the mock anesthesia group, indicating that a single exposure to sevoflurane at subclinical concentrations can precipitate neuronal apoptosis. BMSC treatment did not suppress apoptosis induced by sevoflurane exposure (compared with the vehicle group). The vehicle group had higher proinflammatory cytokine IL-6 protein levels compared with the mock anesthesia group, indicating that sevoflurane exposure induces IL-6 expression. BMSC treatment suppressed sevoflurane-induced increases in IL-6 expression, indicating that these cells can inhibit the neuroinflammation induced by sevoflurane exposure (vehicle group vs. BMSC group).

Conclusions: Intravenous administration of BMSCs reduces neuroinflammation, but does not attenuate apoptosis induced by sevoflurane exposure.

No MeSH data available.


Related in: MedlinePlus