Reactive Astrogliosis after Spinal Cord Injury—Beneficial and Detrimental Effects

Karimi-Abdolrezaee, Soheila; Billakanti, Rohini

doi:10.1007/s12035-012-8287-4

Cited by 291 publications

(244 citation statements)

References 178 publications

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“…Reactive astrogliosis is a pathologic hallmark of spinal cord injury [31]. Astrogliosis is a defense response to minimize and repair the initial damage [32].…”

Section: Discussionmentioning

confidence: 99%

Soluble epoxide hydrolase inhibition provides multi-target therapeutic effects in rats after spinal cord injury

Chen

Huang

et al. 2015

Mol Neurobiol

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Multiple players are involved in motor and sensory dysfunctions after spinal cord injury (SCI). Therefore, therapeutic approaches targeting these various players in the damage cascade hold considerable promise for the treatment of traumatic spinal cord injury. Soluble epoxide hydrolase (sEH) is an endogenous key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids (EETs). sEH inhibition has been shown to provide neuroprotective effects upon multiple elements of neurovascular unit under cerebral ischemia. However, its role in the pathological process after SCI remains unclear. In this study, we tested the hypothesis that sEH inhibition may have therapeutic effects in preventing secondary damage in rats after traumatic SCI. sEH was widely expressed in spinal cord tissue, mainly confined to astrocytes, and neurons. Administration of sEH inhibitor AUDA significantly suppressed local inflammatory responses as indicated by the reduced microglia activation and IL-1 β expression, as well as the decreased infiltration of neutrophils and T lymphocytes. Meanwhile, reactive astrogliosis was remarkably attenuated. Furthermore, treatment of AUDA improved angiogenesis, inhibited neuron cells apoptosis, alleviated demyelination and formation of cavity and improved motor recovery. Together, these results provide the first in vivo evidence that sEH inhibition could exert multiple targets protective effects after SCI in rats. sEH may thereby serve as a promising multi-mechanism therapeutic target for the treatment of SCI.

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“…Reactive astrogliosis is a pathologic hallmark of spinal cord injury [31]. Astrogliosis is a defense response to minimize and repair the initial damage [32].…”

Section: Discussionmentioning

confidence: 99%

Soluble epoxide hydrolase inhibition provides multi-target therapeutic effects in rats after spinal cord injury

Chen

Huang

et al. 2015

Mol Neurobiol

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“…At the acute and subacute stages after SCi, the glial scar serves to seclude the lesion area from healthy tissue by limiting disruption of the blood-spinal cord barrier, the amplification of an overwhelming inflammatory response [83] and massive cellular degeneration [11] . Gradually, the glial scar has its detrimental effect, which is characteristically a long-lasting physical and chemical barrier to axonal regrowth during the chronic period [84,85] .…”

Section: Roles Of Glial Scars In Scimentioning

confidence: 99%

The glial scar in spinal cord injury and repair

2013

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Glial scarring following severe tissue damage and inflammation after spinal cord injury (SCi) is due to an extreme, uncontrolled form of reactive astrogliosis that typically occurs around the injury site. The scarring process includes the misalignment of activated astrocytes and the deposition of inhibitory chondroitin sulfate proteoglycans. Here, we first discuss recent developments in the molecular and cellular features of glial scar formation, with special focus on the potential cellular origin of scar-forming cells and the molecular mechanisms underlying glial scar formation after SCi. Second, we discuss the role of glial scar formation in the regulation of axonal regeneration and the cascades of neuro-inflammation. Last, we summarize the physical and pharmacological approaches targeting the modulation of glial scarring to better understand the role of glial scar formation in the repair of SCi.Keywords: glial scar; spinal cord injury; axonal regeneration; astrocyte activation; reactive astrogliosis; neuroinflammation IntroductionSpinal cord injury (SCi) is a common and devastating central nervous system (CNS) insult that results in disruption of cord microstructure and is followed by limited neuronal regeneration and insufficient functional recovery in adult mammals. After severe SCi, and in response to changes in the local microenvironment, astrocytes, the most abundant glial cells in the CNS, transform into reactive astrocytes and undergo dramatic morphological changes [1] as well as massive variations in gene expression [2] . Reactive astrocytes, the major component of glial scars, along with other cells in the spinal cord and blood-borne cells leaking from the damaged blood-spinal cord barrier, participate in the process of scar formation [3] .From the historical perspective, a glial scar is recognized as an impediment to the regeneration of axons in the cord because of the irregular rearrangement of hypertrophic astrocytic processes, as well as major components of the axonal inhibitory extracellular matrix (ECM), including chondroitin sulfate proteoglycans (CSPGs) that are secreted by the reactive astrocytes [4] . Currently, increasing evidence is advancing our knowledge of the mechanism of the formation of glial scars after a lesion and the roles of glial scars in the regulation of neuro-inflammation and repair processes [5,6] .This article reviews the following: (1) the molecular and cellular properties of glial scar formation following SCi;(2) the roles of glial scar formation in axonal regeneration and neuro-inflammation; and (3) the current status of scarmodulating therapeutic strategies for spinal cord repair after injury. Molecular and Cellular Properties of Glial Scars Characterization of Glial ScarsTraumatic damage of the spinal cord can result in seallike scar tissue in the lesion zone, which is filled with dense cellular components and a connective matrix. Generally, the scar tissue is classified into two parts, fibrotic and glial. 422The fibrotic scar, primarily composed of invading fibrobl...

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“…At the acute and subacute phases after SCI, the reactive astrocytes serve to separate the healthy tissue from the lesion area by restoring the blood-spinal cord barrier (75). This prevents the potential overwhelming inflammatory response (76), massive cellular degeneration and death (77), and tissue damage during the secondary injury (78). Therefore, a number scholars believe that astrogliosis after CNS injury is dependent on STAT3 activation, an indispensable step for the formation of glia scar and limitation of the spread of inflammation (70).…”

Section: Time-dependent Effects Of the Jak-stat Pathway In Reactive Amentioning

confidence: 99%

The role of the JAK-STAT pathway in neural stem cells, neural progenitor cells and reactive astrocytes after spinal cord injury

et al. 2014

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Abstract.Patients with spinal cord injuries can develop severe neurological damage and dysfunction, which is not only induced by primary but also by secondary injuries. As an evolutionarily conserved pathway of eukaryotes, the JAK-STAT pathway is associated with cell growth, survival, development and differentiation; activation of the JAK-STAT pathway has been previously reported in central nervous system injury. The JAK-STAT pathway is directly associated with neurogenesis and glia scar formation in the injury region. Following injury of the axon, the overexpression and activation of STAT3 is exhibited specifically in protecting neurons. To investigate the role of the JAK-STAT pathway in neuroprotection, we summarized the effect of JAK-STAT pathway in the following three sections: Firstly, the modulation of JAK-STAT pathway in proliferation and differentiation of neural stem cells and neural progenitor cells is discussed; secondly, the time-dependent effect of JAK-STAT pathway in reactive astrocytes to reveal their capability of neuroprotection is revealed and lastly, we focus on how the astrocyte-secretory polypeptides (astrocyte-derived cytokines and trophic factors) accomplish neuroprotection via the JAK-STAT pathway.

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Reactive Astrogliosis after Spinal Cord Injury—Beneficial and Detrimental Effects

Cited by 291 publications

References 178 publications

Soluble epoxide hydrolase inhibition provides multi-target therapeutic effects in rats after spinal cord injury

Soluble epoxide hydrolase inhibition provides multi-target therapeutic effects in rats after spinal cord injury

The glial scar in spinal cord injury and repair

The role of the JAK-STAT pathway in neural stem cells, neural progenitor cells and reactive astrocytes after spinal cord injury

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