Intranasal delivery of transforming growth factor-beta1 in mice after stroke reduces infarct volume and increases neurogenesis in the subventricular zone

Ma, Minmin; Ma, Yiming; Yi, Xiaolan; Guo, Ruibing; Zhu, Wusheng; Fan, Xin; Xu, Gelin; Frey, William H.; Liu, Xinfeng

doi:10.1186/1471-2202-9-117

Cited by 123 publications

(84 citation statements)

References 42 publications

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“…Overall, a neuroprotective activity of TGF-␤ signaling for retinal neurons is comparable to the neuroprotective activities of TGF-␤s that were reported for multiple types of neurons throughout the CNS such as in the striatum (Ma et al, 2008), spinal cord (Park et al, 2008), substantia nigra (Roussa et al, 2009), or hippocampus (Zhu et al, 2004. Our results indicate that the protective effects of TGF-␤ signaling on developmental programmed cell death may involve the Smad pathway, including the phosphorylation of Smad3, which decreases in the retina upon conditional inactivation of T␤RII.…”

Section: Tgfb1mentioning

confidence: 53%

TGF- Signaling Protects Retinal Neurons from Programmed Cell Death during the Development of the Mammalian Eye

Braunger

Pielmeier

Demmer

et al. 2013

Journal of Neuroscience

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We investigated the influence of transforming growth factor-␤ (TGF-␤) signaling on developmental programmed cell death in the mouse retina by direct and specific molecular targeting of TGF-␤ type II receptor (T␤RII) and Smad7 in retinal progenitor cells. Mice were generated carrying a conditional deletion of the T␤RII in cells that originate from the inner layer of the optic cup. The animals showed a significant decrease of phosphorylated Smad3 in both the central and peripheral retina, which indicates the diminished activity of TGF-␤ signaling. T␤RII deficiency significantly increased the apoptotic death of retinal neurons during embryonic and postnatal development without affecting their proliferation. In contrast, treatment with TGF-␤2 inhibited cell death of retinal ganglion cells in dissociated retinal cell cultures, an effect that was blocked by inhibiting the phosphorylation of Smad3. The increase in apoptosis during development resulted in a significant reduction in the number of neurons in adult T␤RII-deficient mice. The effect was most pronounced in the inner retina neurons and resulted in functional deficits as determined by electroretinography. In contrast, a conditional deletion of TGF-␤-inhibiting Smad7 in retinal neurons significantly enhanced Smad3 phosphorylation and significantly decreased apoptosis of retinal neurons in embryos and pups. Moreover, the number of retinal ganglion cells was significantly higher in Smad7-deficient mice compared with control littermates. T␤RII-deficient pups showed a lower level of nerve growth factor (NGF) in its mRNA; however, higher levels were observed in Smad7-deficient pups, which strongly suggests that the protective effects of TGF-␤ signaling on developmental cell death are mediated through NGF.

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Section: Tgfb1mentioning

confidence: 53%

TGF- Signaling Protects Retinal Neurons from Programmed Cell Death during the Development of the Mammalian Eye

Braunger

Pielmeier

Demmer

et al. 2013

Journal of Neuroscience

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“…However, other reports show that TGFβ increased neurogenesis in DG after adrenalectomy [121] or in SVZ after stroke [122].…”

Section: Neuronsmentioning

confidence: 83%

The Role of Smad Proteins for Development, Differentiation and Dedifferentiation of Neurons

Ueberham¹,

Arendt²

2013

Trends in Cell Signaling Pathways in Neuronal Fate Decision

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“…Not only intranasal administration is simple and noninvasive, but also avoids potentially dangerous systemic interactions [148][149][150][151] . Positive results were reported following the delivery of growth factors [152][153][154] and MSCs [155][156][157][158] following experimentallyinduced ischemic stroke in rodents. To our knowledge to date, no intranasal delivery trials were conducted on the treatment of ICH using MSCs.…”

Section: Preclinical Studies: An Heterogeneous Approach For An Heteromentioning

confidence: 89%

Stem cell therapy in intracerebral hemorrhage rat model

Cordeiro

Horn

2015

WJSC

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Intracerebral hemorrhage (ICH) is a very complex pathology, with many different not fully elucidated etiologies and prognostics. It is the most severe subtype of stroke, with high mortality and morbidity rates. Unfortunately, despite the numerous promising preclinical assays including neuroprotective, anti-hypertensive, and anti-inflammatory drugs, to this moment only symptomatic treatments are available, motivating the search for new alternatives. In this context, stem cell therapy emerged as a promising tool. However, more than a decade has passed, and there is still much to be learned not only about stem cells, but also about ICH itself, and how these two pieces come together. To date, rats have been the most widely used animal model in this research field, and there is much more to be learned from and about them. In this review, we first summarize ICH epidemiology, risk factors, and pathophysiology. We then present different methods utilized to induce ICH in rats, and examine how accurately they represent the human disease. Next, we discuss the different types of stem cells used in previous ICH studies, also taking into account the tested transplantation sites. Finally, we summarize what has been achieved in assays with stem cells in rat models of ICH, and point out some relevant issues where attention must be given in future efforts. Core tip: In this review, we first summarize intracerebral hemorrhage (ICH) epidemiology, risk factors, and pathophysiology. We then present different methods utilized to induce ICH in rats, and examine how accurately they represent the human disease. Next, we discuss the different types of stem cells used in previous ICH studies, also taking into account the tested transplantation sites. Finally, we summarize what has been achieved in assays with stem cells in rat models of ICH, and point out some relevant issues where attention must be given in future efforts.Cordeiro MF, Horn AP. Stem cell therapy in intracerebral hemorrhage rat model. World J Stem Cells 2015; 7(3): 618-629

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Intranasal delivery of transforming growth factor-beta1 in mice after stroke reduces infarct volume and increases neurogenesis in the subventricular zone

Abstract: Background: The effect of neurotrophic factors in enhancing stroke-induced neurogenesis in the adult subventricular zone (SVZ) is limited by their poor blood-brain barrier (BBB) permeability.

Cited by 123 publications

References 42 publications

TGF- Signaling Protects Retinal Neurons from Programmed Cell Death during the Development of the Mammalian Eye

TGF- Signaling Protects Retinal Neurons from Programmed Cell Death during the Development of the Mammalian Eye

The Role of Smad Proteins for Development, Differentiation and Dedifferentiation of Neurons

Stem cell therapy in intracerebral hemorrhage rat model

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