Comparison of the therapeutic effects of bone marrow mononuclear cells and microglia for permanent cerebral ischemia - PubMed (original) (raw)

Comparative Study

Comparison of the therapeutic effects of bone marrow mononuclear cells and microglia for permanent cerebral ischemia

Chao Jiang et al. Behav Brain Res. 2013.

Abstract

In this study we transplanted bone marrow mononuclear cells (BM-MNCs) or microglia into rats that had undergone permanent cerebral ischemia and observed the distribution or morphology of transplanted cells in vivo. In addition, we compared the effects of BM-MNCs and microglia on infarct volume, brain water content, and functional outcome after permanent cerebral ischemia. BM-MNCs and microglia were obtained from femur and brain, respectively, of newborn rats. Adult rats were injected with vehicle or 3 million BM-MNCs or microglia via the tail vein 24h after permanent middle cerebral artery occlusion (pMCAO). The distribution or morphologic characteristics of transplanted BM-MNCs (double stained with BrdU/Cd34 or BrdU/CD45) and microglia (double stained with BrdU/Iba-1) were detected with immunofluorescent staining at 3 or 7 and 14 days after pMCAO. Functional deficits were assessed by the modified neurologic severity score at 1, 3, 7 and 14 days after pMCAO. Brain water content was assessed at 3 days, and infarct volume was determined at 14 days. We observed more BrdU/CD45 and BrdU/Iba-1 double-stained cells than BrdU/CD34 double-stained cells around the infarcted area. Some infused microglia showed the morphology of innate microglia at 7 days after pMCAO, and the number increased at 14 days. BM-MNC-treated rats showed significantly reduced infarct volume and brain water content compared to vehicle- and microglia-treated rats. In addition, BM-MNC treatment reduced neurologic deficit scores compared to those in the other groups. The results provide evidence that infusion of BM-MNCs, but not microglia, is neuroprotective after permanent cerebral ischemia.

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Figures

Fig. 1

Fig. 1

Migration of microglia and BM-MNCs in vivo. Immunofluorescence staining for BrdU-labeled cells revealed that both microglia (A) and BM-MNCs (B) migrated to the boundary zone of the injured cortex in rats after infusion via the tail vein on day 3 after pMCAO. There are more CD45-positive cells (D) around the infarcted area than CD34 cells (C) (n = 4 rats per group). Scale bar = 50 μm.

Fig. 2

Fig. 2

The number of transplanted microglia and BM-MNCs in vivo. There are more BrdU/double-stained CD45 and Iba-1 cells than BrdU/double-stained CD34 around the infarcted area at 3 days after pMCAO (A–I). Scale bar = 50 μm.

Fig. 3

Fig. 3

The morphologic characteristics of transplanted primary microglia in vivo. The transplanted primary microglia did not show a ramified or an activated/amoeboid morphology at 3 days after pMCAO and only a few of them show a ramified or an activated/amoeboid morphology from 7 days after pMCAO. More infused primary microglia can be detected to show a ramified or an activated/amoeboid morphology (A–I). Scale bar = 50 μm.

Fig. 4

Fig. 4

Effect of BM-MNC and microglia treatment on brain water content. Statistical analysis showed significant difference among the five groups (F = 7.37, n = 6 rats per group, P < 0.001). Post hoc analysis revealed that only BM-MNC treatment produced a significant reduction in brain water content. *P < 0.05 vs. untreated, vehicle-treated, and microglia-treated groups.

Fig. 5

Fig. 5

Treatment with BM-MNCs reduces infarct volume after pMCAO. (A) Representative images of TTC-stained brain slices from vehicle-treated (top), microglia-treated rats (middle) and BM-MNC-treated rats (bottom) at 14 days post-pMCAO. (B) Quantification shows that the infarct volume of BM-MNC-treated rats was significantly smaller than that of untreated, vehicle-treated, and microglia-treated rats (F = 30.80, n = 6 rats per group, P < 0.001). *P < 0.05 vs. any other group.

Fig. 6

Fig. 6

Treatment with BM-MNCs reduces neurologic deficit after pMCAO. ANOVA revealed a significant difference in neurologic function among untreated, vehicle-treated, microglia-treated, and BM-MNC-treated groups on days 1, 3, 7 and 14 after pMCAO (F value for tests of between-subject effect = 9.33, P < 0.001). Treatment with BM-MNCs significantly improved neurologic function on day 14 compared to that in untreated, vehicle-treated, and microglia-treated groups (n = 10 rats per group). *P < 0.05 vs. all other groups.

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