Bridging the gap of axonal regeneration in the central nervous system: A state of the art review on central axonal regeneration

Costa, Gustavo; Ribeiro, Filipa F.; Sebastião, Ana M.; Muir, Elizabeth M.; Vaz, Sandra H.

doi:10.3389/fnins.2022.1003145

Cited by 11 publications

(4 citation statements)

References 214 publications

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“…Both beneficial and detrimental roles have been attributed to the glial scar and reactive astrocytes (reviewed in Ding et al (2021) ). Among the detrimental roles is the impediment of axonal regrowth, partly due to the release of inhibitory factors by reactive astrocytes [reviewed in Costa et al (2022)] . Astrocyte activation and astrogliosis are paralleled by increased GFAP expression.…”

Section: Resultsmentioning

confidence: 99%

Cypin Inhibition as a Therapeutic Approach to Treat Spinal Cord Injury–Induced Mechanical Pain

Singh,

Gandu,

et al. 2024

eNeuro

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Cypin (cytosolicpostsynaptic density protein 95interactor) is the primary guanine deaminase (GDA) in the central nervous system (CNS), promoting the metabolism of guanine to xanthine, an important reaction in the purine salvage pathway. Activation of the purine salvage pathway leads to the production of uric acid (UA). UA has paradoxical effects, specifically in the context of CNS injury as it confers neuroprotection, but it also promotes pain. Since neuropathic pain is a comorbidity associated with spinal cord injury (SCI), we postulated that small molecule cypin inhibitor B9 treatment could attenuate SCI-induced neuropathic pain, potentially by interfering with UA production. However, we also considered that this treatment could hinder the neuroprotective effects of UA, and in doing so, exacerbate SCI outcomes. To address our hypothesis, we induced a moderate mid-thoracic contusion SCI in female mice and assessed whether transient intrathecal administration of B9, starting at 1 day post injury (pi) until 7 days pi, attenuates mechanical pain in hindlimbs at 3 weeks pi. We also evaluated the effects of B9 on the spontaneous recovery of locomotor function. We found that B9 alleviates mechanical pain but does not affect locomotor function. Importantly, B9 does not exacerbate lesion volume at the epicenter. In accordance with these findings, B9 does not aggravate glutamate-induced excitotoxic death of SC neuronsin vitro. Moreover, SCI-induced increased astrocyte reactivity at the glial scar is not altered by B9 treatment. Our data suggest that B9 treatment reduces mechanical pain without exerting major detrimental effects following SCI.Statement of SignificanceNeuropathic pain is a debilitating comorbidity associated with spinal cord injury (SCI). Available pharmacological therapies are ineffective or have adverse effects. Development of new and targeted drugs that can effectively alleviate neuropathic pain is urgently needed. Cypin is the primary guanine deaminase in the central nervous system and an essential enzyme in the purine salvage pathway. Activation of the purine salvage pathway leads to production of uric acid, which promotes pain, but also, neuroprotection. We found that inhibition of cypin post-SCI alleviates mechanical pain. The inhibitor does not prevent the spontaneous recovery of locomotor function or exacerbate lesion volume and astrogliosis at the injury epicenter. Thus, cypin inhibitors could be promising therapies for the treatment of neuropathic pain.

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Section: Resultsmentioning

confidence: 99%

Cypin Inhibition as a Therapeutic Approach to Treat Spinal Cord Injury–Induced Mechanical Pain

Singh,

Gandu,

et al. 2024

eNeuro

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“…Cell-based therapies have shown great promise by targeting damaged axonal pathways. Still, the strategies proposed are not designed to restore long-distance axons; novel strategies enhance axons’ intrinsic ability to regenerate and create a permissive environment for axonal outgrowth [ 8 , 62 , 63 ]. Transplantable “scaffolds” have recently been used to facilitate axon regeneration.…”

Section: The Nervous Systemmentioning

confidence: 99%

Injectable Hydrogels for Nervous Tissue Repair—A Brief Review

Politrón-Zepeda,

Fletes-Vargas,

Rodríguez-Rodríguez

2024

Gels

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The repair of nervous tissue is a critical research field in tissue engineering because of the degenerative process in the injured nervous system. In this review, we summarize the progress of injectable hydrogels using in vitro and in vivo studies for the regeneration and repair of nervous tissue. Traditional treatments have not been favorable for patients, as they are invasive and inefficient; therefore, injectable hydrogels are promising for the treatment of damaged tissue. This review will contribute to a better understanding of injectable hydrogels as potential scaffolds and drug delivery system for neural tissue engineering applications.

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“…Localization of reactive astrocytes that display changed morphology depends on the proximity to the insult. Studies have shown that astrocytes close to the injury site have shown greater elongation of processes as compared to astrocytes that are localized further away from the injury site [240].…”

Section: Differences In Localization Age and The Type Of Injurymentioning

confidence: 99%

Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury

Czyżewski,

Mazurek,

Sakwa

et al. 2024

Cells

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Traumatic Brain Injury (TBI) represents a significant health concern, necessitating advanced therapeutic interventions. This detailed review explores the critical roles of astrocytes, key cellular constituents of the central nervous system (CNS), in both the pathophysiology and possible rehabilitation of TBI. Following injury, astrocytes exhibit reactive transformations, differentiating into pro-inflammatory (A1) and neuroprotective (A2) phenotypes. This paper elucidates the interactions of astrocytes with neurons, their role in neuroinflammation, and the potential for their therapeutic exploitation. Emphasized strategies encompass the utilization of endocannabinoid and calcium signaling pathways, hormone-based treatments like 17β-estradiol, biological therapies employing anti-HBGB1 monoclonal antibodies, gene therapy targeting Connexin 43, and the innovative technique of astrocyte transplantation as a means to repair damaged neural tissues.

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Bridging the gap of axonal regeneration in the central nervous system: A state of the art review on central axonal regeneration

Cited by 11 publications

References 214 publications

Cypin Inhibition as a Therapeutic Approach to Treat Spinal Cord Injury–Induced Mechanical Pain

Cypin Inhibition as a Therapeutic Approach to Treat Spinal Cord Injury–Induced Mechanical Pain

Injectable Hydrogels for Nervous Tissue Repair—A Brief Review

Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury

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