Neuroprotection by cord blood stem cells against glutamate-induced apoptosis is mediated by Akt pathway

Dasari, Venkata Ramesh; Veeravalli, Krishna Kumar; Saving, Kay L.; Gujrati, Meena; Fassett, Dan; Klopfenstein, Jeffrey D.; Dinh, Dzung H.; Rao, Jasti S.

doi:10.1016/j.nbd.2008.09.005

Cited by 55 publications

(48 citation statements)

References 42 publications

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“…This protective effect may come from the stimulation of Erβ, which activates the estrogen response element of the Bcl-2 gene, and then increases transcription and translation to up regulate the expression of Bcl-2 [35]. Dasari et al [65] found that intravenous administration of HUCB-MSCs modulates the expression of proteins involved in cell survival. Also, HUCB-MSCs were found to up regulate Bcl-2 protein expression in the cerebellum of ataxic rats, which enhanced the survival of different types of neurons, including those of the granular layer.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Mesenchymal Stem Cells vs. Estradiol Benzoate or Avosoya on the Cerebellar Cortex of Ovariectomized Adult Albino Rats

Ahmed¹,

Abdelrahman²,

Shalaby³

2017

J Cytol Histol

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Alterations in hormone levels during menopause affect cognitive function and brain chemistry. Stem cell therapy in nervous system disorders is a growing field. The present research aimed to compare the effect of MSCs with that of estradiol benzoate or avosoya on the cerebellum of ovariectomized rats. Fifty eight adult female Wistar albino rats were classified into five groups. Control group (Group I) and four ovariectomized groups. Group II (ovariectomized rats received no treatment), Group III (injected subcutaneously with estradiol benzoate), Group IV (received avosoya orally) and Group V (treated with human umbilical cord blood derived mesenchymal stem cells [HUCBMSCs]). Cerebellar sections were stained with hematoxylin and eosin and cresyl fast violet. Immunoperoxidase reaction of glial fibrillary acidic protein (GFAP), estrogen receptor beta (Erβ) and Bax protein was also done. HUCBMSCs homing in rat cerebellum were detected by human albumin gene. Antioxidant enzyme levels were also measured in cerebellum homogenate. Decreased density of neurons in the three cortical layers with vacuolations and distorted Purkinje cells with pyknotic nuclei were observed in Group II. Group III cerebellar cortex showed normal architecture but some Purkinje cells had pyknotic nuclei. Group IV showed normal neuronal cells in the three cortical layers. Group V Purkinje cells were pyriform with vesicular nuclei, and basophilic cytoplasm. Small rounded cells with deeply stained nuclei appeared in the granular layer. In conclusion: estradiol benzoate and avosoya improve ovariectomy-induced cerebellar alteration, and MSCs show promising results in this field.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Mesenchymal Stem Cells vs. Estradiol Benzoate or Avosoya on the Cerebellar Cortex of Ovariectomized Adult Albino Rats

Ahmed¹,

Abdelrahman²,

Shalaby³

2017

J Cytol Histol

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“…These results suggest that cytokines could induce neuronal apoptosis through a variety of pathways. Dasari and his colleagues [35] found that the mechanism underlying hUCB neuroprotection involves the activation of the Akt signaling pathway. Their research identified the neuroprotective potential of hUCB against glutamate-induced apoptosis in cultured cortical neurons.…”

Section: Discussionmentioning

confidence: 99%

Human umbilical cord blood mesenchymal stem cell transplantation suppresses inflammatory responses and neuronal apoptosis during early stage of focal cerebral ischemia in rabbits

et al. 2014

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Aim: Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) have been shown to ameliorate cerebral ischemia in animal models. In this study we investigated the effects of hUCB-MSCs on inflammatory responses and neuronal apoptosis during the early stage of focal cerebral ischemia in rabbits. Methods: Focal cerebral ischemia was induced in male New Zealand rabbits by occlusion of MCA for 2 h. The blood samples were collected at different time points prior and during MCAO-reperfusion. The animals were euthanized 3 d after MCAO, and the protein levels of IL-1β, IL-6, IL-10, and TNF-α in the serum and peri-ischemic brain tissues were detected using Western blot and ELISA, respectively. Inflammatory cell infiltration, neuronal apoptosis and neuronal density were measured morphologically. hUCB-MSCs (5×10 6 ) were iv injected a few minutes after MCAO. Results: The serum levels of IL-1β, IL-6, and TNF-α were rapidly increased, and peaked at 2 h after the start of MCAO. hUCB-MSC transplantation markedly and progressively suppressed the ischemia-induced increases of serum IL-1β, IL-6, and TNF-α levels within 6 h MCAO-reperfusion. Focal cerebral ischemia decreased the serum level of IL-10, which was prevented by hUCB-MSC transplantation. The expression of IL-1β, IL-6, IL-10, and TNF-α in the peri-ischemic brain tissues showed similar changes as in the serum. hUCB-MSC transplantation markedly suppressed the infiltration of inflammatory cells, and increased the neuronal density around the ischemic region. Furthermore, hUCB-MSC transplantation significantly decreased the percentage of apoptosis around the ischemic region. Conclusion: hUCB-MSCs transplantation suppresses inflammatory responses and neuronal apoptosis during the early stage focal cerebral ischemia in rabbits.

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“…Upon phosphorylation, Akt transduces survival signals by inhibiting apoptotic cascades and promoting activation of cell survival pathways (11,12). Indeed, previous studies have shown that HUCB cells protect cultured neurons from excitotoxic injury through activation of Akt (13).…”

Section: Human Umbilical Cord Blood (Hucb)mentioning

confidence: 99%

Human Umbilical Cord Blood Cells Protect Oligodendrocytes from Brain Ischemia through Akt Signal Transduction

Rowe

Leonardo

Recio

et al. 2012

Journal of Biological Chemistry

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Background: Human umbilical cord blood cells are an effective experimental treatment for stroke. Results: These cells activate Akt to increase peroxiredoxin 4 and are essential for oligodendrocyte survival during ischemia. Conclusion: Akt and peroxiredoxin 4 are key molecules in transducing the cellular protection elicited by cord blood cells. Significance: Identifying this signaling pathway provides new pharmaceutical targets for stroke treatment.

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Neuroprotection by cord blood stem cells against glutamate-induced apoptosis is mediated by Akt pathway

Cited by 55 publications

References 42 publications

Therapeutic Potential of Mesenchymal Stem Cells vs. Estradiol Benzoate or Avosoya on the Cerebellar Cortex of Ovariectomized Adult Albino Rats

Therapeutic Potential of Mesenchymal Stem Cells vs. Estradiol Benzoate or Avosoya on the Cerebellar Cortex of Ovariectomized Adult Albino Rats

Human umbilical cord blood mesenchymal stem cell transplantation suppresses inflammatory responses and neuronal apoptosis during early stage of focal cerebral ischemia in rabbits

Human Umbilical Cord Blood Cells Protect Oligodendrocytes from Brain Ischemia through Akt Signal Transduction

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