bFGF and EGF modulate trauma-induced proliferation and neurogenesis in juvenile organotypic hippocampal slice cultures

Laskowski, Alexandra; Schmidt, Werner; Dinkel, Klaus; Martinez-Sanchez, Monica; Reymann, Klaus G.

doi:10.1016/j.brainres.2004.12.035

Cited by 31 publications

(18 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, we observed that EGF further enhances cell proliferation in the DG in injured animals. This is also supported by an organotypic hippocampal slice culture study, in which the authors demonstrated that following transection of CA2 Schaffer collaterals, EGF increased trauma-induced cell proliferation in the DG, but not neurogenesis (Laskowski et al, 2005). This disparity in the effects of EGF on cell proliferation in the DG could be due to differences between injured versus normal animals or the length of EGF administration, as well as differing sampling or quantification methods.…”

Section: Discussionsupporting

confidence: 51%

The Effect of Epidermal Growth Factor in the Injured Brain after Trauma in Rats

Sun

Bullock

Altememi

et al. 2010

Journal of Neurotrauma

105

View full text Add to dashboard Cite

Epidermal growth factor (EGF) is a known mitogen for neural stem and progenitor cells (NS=NPCs) in the central nervous system (CNS). In vitro, EGF maintains NS=NPCs in the proliferative state, whereas in the normal rodent brain it promotes their proliferation and migration in the subventricular zone (SVZ). Additionally, EGF administration can augment neuronal replacement in the ischemic-injured adult striatum. Recently we found that the SVZ and the hippocampus display an injury-induced proliferative response following traumatic brain injury (TBI) that is linked to increased EGF expression. As adult neurogenesis is associated with cognitive function, we hypothesized that post-TBI administration of EGF could affect neurogenesis and cognitive recovery. Adult rats were intraventricularly infused with EGF or vehicle for 7 days following TBI. 5-Bromo-2-deoxyuridine (BrdU) was administered to label proliferating cells and the animals were sacrificed at 1 or 4 weeks post-injury. Using immunohistochemistry and stereology, we found that at 1 week post-injury, compared to vehicle-infused animals EGF-infused animals had significantly more BrdU-positive cells in the SVZ and hippocampus concomitant with enhanced EGF receptor expression. At 4 weeks post-injury, the number of BrdUpositive cells in the hippocampus was similar in both groups, suggesting that EGF does not support long-term survival of newly generated cells. Furthermore, we found that the EGF-induced proliferative population differentiated preferentially toward astroglial phenotype. Nevertheless, animals treated with EGF showed significant improvement in cognitive function, which was accompanied by reduced hippocampal neuronal cell loss. Collectively, the data from this study demonstrate that EGF exerts a neuroprotective rather than neurogenic effect in protecting the brain from injury.

show abstract

Section: Discussionsupporting

confidence: 51%

The Effect of Epidermal Growth Factor in the Injured Brain after Trauma in Rats

Sun

Bullock

Altememi

et al. 2010

Journal of Neurotrauma

105

View full text Add to dashboard Cite

show abstract

“…51,52 In contradistinction to this reduction in GFAP expression, DCX mRNA expression was significantly increased in MSC-treated hippocampi compared with controls (Figure 4b), indicating an increased number of newly formed neurons in the hippocampus. Similarly, the mRNA of FGF-2, a potent modulator of hippocampal neurogenesis, 53,54 increased significantly in MSCtreated hippocampi compared with controls ( Figure 4b). In contradistinction to FGF-2, IGF-1 mRNA expression was slightly reduced in MSC-treated hippocampi (Figure 4b).…”

Section: Discussionmentioning

confidence: 84%

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

et al. 2009

View full text Add to dashboard Cite

Adult bone marrow-derived mesenchymal stem cells (MSCs) are regarded as potential candidates for treatment of neurodegenerative disorders, because of their ability to promote neurogenesis. MSCs promote neurogenesis by differentiating into neural lineages as well as by expressing neurotrophic factors that enhance the survival and differentiation of neural progenitor cells. Depression has been associated with impaired neurogenesis in the hippocampus and dentate gyrus. Therefore, the aim of this study was to analyze the therapeutic potential of MSCs in the Flinders sensitive line (FSL), a rat animal model for depression. Rats received an intracerebroventricular injection of culture-expanded and 1,1 0 -dioctadecyl-3,3,3 0 ,3 0 -tetramethylindocarbocyanine perchlorate (DiI)-labeled bone marrow-derived MSCs (10 5 cells). MSC-transplanted FSL rats showed significant improvement in their behavioral performance, as measured by the forced swim test and the dominant-submissive relationship (DSR) paradigm. After transplantation, MSCs migrated mainly to the ipsilateral dentate gyrus, CA1 and CA3 regions of the hippocampus, and to a lesser extent to the thalamus, hypothalamus, cortex and contralateral hippocampus. Neurogenesis was increased in the ipsilateral dentate gyrus and hippocampus of engrafted rats (granular cell layer) and was correlated with MSC engraftment and behavioral performance. We therefore postulate that MSCs may serve as a novel modality for treating depressive disorders.

show abstract

“…Hippocampal slice cultures were used as a target tissue, since i) they are well established and widely used as CNS organotypic cultures containing several well-described nerve fibers [10], and ii) they preserve regions of neurogenic activity and demonstrate neural progenitor proliferation and differentiation [11]. Hence, hippocampal slice cultures served as a host tissue for MSC / NPC transplantation and survival and differentiation of the transplanted NPCs were investigated.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells Promote Oligodendroglial Differentiation in Hippocampal Slice Cultures

Rivera

Siebzehnrubl²,

Kandasamy³

et al. 2009

Cell Physiol Biochem

View full text Add to dashboard Cite

We have previously shown that soluble factors derived from mesenchymal stem cells (MSCs) induce oligodendrogenic fate and differentiation in adult rat neural progenitors (NPCs) in vitro. Here, we investigated if this pro-oligodendrogenic effect is maintained after cells have been transplanted onto rat hippocampal slice cultures, a CNS-organotypic environment. We first tested whether NPCs, that were pre-differentiated in vitro by MSC-derived conditioned medium, would generate oligodendrocytes after transplantation. This approach resulted in the loss of grafted NPCs, suggesting that oligodendroglial pre-differentiated cells could not integrate in the tissue and therefore did not survive grafting. However, when NPCs together with MSCs were transplanted in situ into hippocampal slice cultures, the grafted NPCs survived and the majority of them differentiated into oligodendrocytes. In contrast to the prevalent oligodendroglial differentiation in case of the NPC/MSC co-transplantation, naïve NPCs transplanted in the absence of MSCs differentiated predominantly into astrocytes. In summary, the pro-oligodendrogenic activity of MSCs was maintained only after co-transplantation into hippocampal slice cultures. Therefore, in the otherwise astrogenic milieu, MSCs established an oligodendrogenic niche for transplanted NPCs, and thus, co-transplantation of MSCs with NPCs might provide an attractive approach to re-myelinate the various regions of the diseased CNS.

show abstract

bFGF and EGF modulate trauma-induced proliferation and neurogenesis in juvenile organotypic hippocampal slice cultures

Cited by 31 publications

References 44 publications

The Effect of Epidermal Growth Factor in the Injured Brain after Trauma in Rats

The Effect of Epidermal Growth Factor in the Injured Brain after Trauma in Rats

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

Mesenchymal Stem Cells Promote Oligodendroglial Differentiation in Hippocampal Slice Cultures

Contact Info

Product

Resources

About