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Glial Cell Line-Derived Neurotrophic Factor and Focal Ischemic Stroke

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Abstract

Focal ischemic stroke (FIS) is a leading cause of human debilitation and death. Following the onset of a FIS, the brain experiences a series of spatiotemporal changes which are exemplified in different pathological processes. One prominent feature of FIS is the development of reactive astrogliosis and glial scar formation in the peri-infarct region (PIR). During the subacute phase, astrocytes in PIR are activated, referred to as reactive astrocytes (RAs), exhibit changes in morphology (hypotrophy), show an increased proliferation capacity, and altered gene expression profile, a phenomenon known as reactive astrogliosis. Subsequently, the morphology of RAs remains stable, and proliferation starts to decline together with the formation of glial scars. Reactive astrogliosis and glial scar formation eventually cause substantial tissue remodeling and changes in permanent structure around the PIR. Glial cell line-derived neurotrophic factor (GDNF) was originally isolated from a rat glioma cell-line and regarded as a potent survival neurotrophic factor. Under normal conditions, GDNF is expressed in neurons but is upregulated in RAs after FIS. This review briefly describes properties of GDNF, its receptor-mediated signaling pathways, as well as recent studies regarding the role of RAs-derived GDNF in neuronal protection and brain recovery. These results provide evidence suggesting an important role of RA-derived GDNF in intrinsic brain repair and recovery after FIS, and thus targeting GDNF in RAs may be effective for stroke therapy.

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Fig. 1

Adapted from reference Li et al.

Fig. 2

Adapted from Kramer and Liss

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Acknowledgements

This work was supported by the National Institute of Health [National Institute of Neurological Disorders and Stroke (NINDS) Grants R01NS069726 and R01NS094539 to SD] and the America Heart Association [Midwest Affiliate Grant-in-Aid (Grant No. 16GRNT31280014), and NCRG-IRG 16IRG27780023 to SD].

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Authors and Affiliations

  1. Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, MO, 65211, USA

    Zhe Zhang & Shinghua Ding

  2. Department of Biomedical, Biological and Chemical Engineering, University of Missouri-Columbia, Columbia, MO, 65211, USA

    Zhe Zhang & Shinghua Ding

  3. Department of Biochemistry, University of Missouri-Columbia, Columbia, MO, 65211, USA

    Grace Y. Sun

  4. Dalton Cardiovascular Research Center, Department of Biomedical, Biological and Chemical Engineering, University of Missouri-Columbia, 134 Research Park Drive, Columbia, MO, 65211, USA

    Shinghua Ding

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  1. Zhe Zhang
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ZZ-original draft preparation; GS-review and editing; SD-review, editing and supervision. All authors read and approved the final manuscript.

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Correspondence to Shinghua Ding.

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Zhang, Z., Sun, G.Y. & Ding, S. Glial Cell Line-Derived Neurotrophic Factor and Focal Ischemic Stroke. Neurochem Res 46, 2638–2650 (2021). https://doi.org/10.1007/s11064-021-03266-5

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