Enhancement of endogenous neurogenesis in ephrin-B3 deficient mice after transient focal cerebral ischemia
Open accessAbstract
Cerebral ischemia stimulates endogenous neurogenesis. However, the functional relevance of this phenomenon remains unclear because of poor survival and low neuronal differentiation rates of newborn cells. Therefore, further studies on mechanisms regulating neurogenesis under ischemic conditions are required, among which ephrin-ligands and ephrin-receptors (Eph) are an interesting target. Although Eph/ephrin proteins like ephrin-B3 are known to negatively regulate neurogenesis under physiological conditions, their role in cerebral ischemia is largely unknown. We therefore studied neurogenesis, brain injury and functional outcome in ephrin-B3(-/-) (knockout) and ephrin-B3(+/+) (wild-type) mice submitted to cerebral ischemia. Induction of stroke resulted in enhanced cell proliferation and neuronal differentiation around the lesion site of ephrin-B3(-/-) compared to ephrin-B3(+/+) mice. However, prominent post-ischemic neurogenesis in ephrin-B3(-/-) mice was accompanied by significantly increased ischemic injury and motor coordination deficits that persisted up to 4 weeks. Ischemic injury in ephrin-B3(-/-) mice was associated with a caspase-3-dependent activation of the signal transducer and activator of transcription 1 (STAT1). Whereas inhibition of caspase-3 had no effect on brain injury in ephrin-B3(+/+) animals, infarct size in ephrin-B3(-/-) mice was strongly reduced, suggesting that aggravated brain injury in these animals might involve a caspase-3-dependent activation of STAT1. In conclusion, post-ischemic neurogenesis in ephrin-B3(-/-) mice is strongly enhanced, but fails to contribute to functional recovery because of caspase-3-mediated aggravation of ischemic injury in these animals. Our results suggest that ephrin-B3 might be an interesting target for overcoming some of the limitations of further cell-based therapies in stroke.
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Enhanced neurogenesis is associated with enhanced neuronal survival in most but not all conditions; in a study of ephrin-B3 deficiency, proliferation and survival of endogenous neural precursor cells were enhanced but ischaemic injury was exacerbated.
“Enhanced neurogenesis is associated with enhanced neuronal survival in most but not all conditions: in a recent study examining effects of ephrin-B3 deficiency, enhanced proliferation and survival of endogenous neural precursor cells but exacerbation of ischaemic injury were reported.99”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [99]
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- Authors
- Doeppner, T. R., Bretschneider, E., Doehring, M., Segura, I., Sentürk, A., Acker-Palmer, A., Hasan, M. R., ElAli, A., Hermann, D. M., & Bähr, M.
- Affiliations
- Universitätsmedizin Göttingen (DE)
- Goethe University Frankfurt (DE)
- University of Duisburg-Essen (DE)
- Corresponding author
- Doeppner, Thorsten R.
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2011-07-21
- Volume
- 122
- Issue
- 4
- Pages
- 429-42
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC3291816
- OpenAlex
- W2073574628
- Cited by
- 43
- References
- 48
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 10 · 2013: 5 · 2012: 4
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Acta Neuropathologica (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- GRO (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (DFG EXC115, (EXC 115).)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- ephrin-B3, endogenous neurogenesis, transient focal cerebral ischemia, stroke, Eph receptors, caspase-3, STAT1, infarct size, neuronal differentiation, cell proliferation, motor coordination deficits, cell therapy, knockout mice
- MeSH terms
- Animals, Brain Ischemia, Disease Models, Animal, Male, Time Factors, Up-Regulation, Mice, Knockout, Ephrin-B3, Mice, Neurogenesis
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