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Reactive Astrogliosis after Spinal Cord Injury—Beneficial and Detrimental Effects

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Abstract

Reactive astrogliosis is a pathologic hallmark of spinal cord injury (SCI). It is characterised by profound morphological, molecular, and functional changes in astrocytes that occur within hours of SCI and evolves as time elapses after injury. Astrogliosis is a defense mechanism to minimize and repair the initial damage but eventually leads to some detrimental effects. Reactive astrocytes secrete a plethora of both growth promoting and inhibitory factors after SCI. However, the production of inhibitory components surpasses the growth stimulating factors, thus, causing inhibitory effects. In severe cases of injury, astrogliosis results in the formation of irreversible glial scarring that acts as regeneration barrier due to the expression of inhibitory components such as chondroitin sulfate proteoglycans. Scar formation was therefore recognized from a negative perspective for many years. Accumulating evidence from pharmacological and genetic studies now signifies the importance of astrogliosis and its timing for spinal cord repair. These studies have advanced our knowledge regarding signaling pathways and molecular mediators, which trigger and modulate reactive astrocytes and scar formation. In this review, we discuss the recent advances in this field. We also review therapeutic strategies that have been developed to target astrocytes reactivity and glial scaring in the environment of SCI. Astrocytes play pivotal roles in governing SCI mechanisms, and it is therefore crucial to understand how their activities can be targeted efficiently to harness their potential for repair and regeneration after SCI.

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Abbreviations

BBB:

Blood–brain barrier

BSB:

Blood–spinal barrier

BMPs:

Bone morphogenetic proteins

ChABC:

Chondroitin sulfate proteoglycans

CSPGs:

Chondroitin sulfate proteoglycans

CNS:

Central nervous system

Eph:

Ephrin

ECM:

Extracellular matrix

GFAP:

Glial fibrillary acidic proteins

GAG:

Glycosaminoglycans

IL:

Interleukin

NPCs:

Neural precursor cells

OPCs:

Oligodendrocyte precursor cells

RPTP:

Receptor protein tyrosine phosphatases

SCI:

Spinal cord injury

Stat3:

Signal transducers and activators of transcription3

TGF:

Transforming growth factors

TNF-α:

Tumor necrosis factor-alpha

XT:

Xylosyltransferase

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  1. Regenerative Medicine Program, Departments of Physiology and Biochemistry and Medical Genetics, the Spinal Cord Research Center, University of Manitoba, 629 Basic Medical Sciences Building, Winnipeg, MB R3E 0J9, Canada

    Soheila Karimi-Abdolrezaee & Rohini Billakanti

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  1. Soheila Karimi-Abdolrezaee
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Correspondence to Soheila Karimi-Abdolrezaee.

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Karimi-Abdolrezaee, S., Billakanti, R. Reactive Astrogliosis after Spinal Cord Injury—Beneficial and Detrimental Effects. Mol Neurobiol 46, 251–264 (2012). https://doi.org/10.1007/s12035-012-8287-4

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