Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System

Bighinati, Andrea; Focarete, Maria Letizia; Gualandi, Chiara; Pannella, Micaela; Giuliani, Alessandro; Beggiato, Sarah; Ferraro, Luca; Lorenzini, Luca; Giardino, Luciana; Calzà, Laura

doi:10.1089/neu.2019.6949

Cited by 17 publications

(11 citation statements)

References 55 publications

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“…The areas directly affected by the Impactor tip included the gray matter (dorsal and part of the ventral horn) and the white matter with regard to the dorsal funiculus, which includes the ascending fasciculus gracilis and the descending corticospinal tracts. Following contusion injury, the lesion developed a cystic cavity at the center of the lesion, which spread coronally and longitudinally in both rostral and caudal directions from the 1.5 mm wide impact, extending for more than 4.0 mm across the center of the lesion at 3 DPL, then expanding further, surrounded by scar tissue, an evolution which corresponds to the literature in the field [4,[22][23][24]. Quantitative MRI indicated that most of the axons directly affected by the impact degenerated rostrally to the injury site, while minor damage was observed caudally [25].…”

Section: Discussionsupporting

confidence: 70%

Time-Course Changes of Extracellular Matrix Encoding Genes Expression Level in the Spinal Cord Following Contusion Injury—A Data-Driven Approach

Bighinati

Khalajzeyqami

Baldassarro

et al. 2021

IJMS

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The involvement of the extracellular matrix (ECM) in lesion evolution and functional outcome is well recognized in spinal cord injury. Most attention has been dedicated to the “core” area of the lesion and scar formation, while only scattered reports consider ECM modification based on the temporal evolution and the segments adjacent to the lesion. In this study, we investigated the expression profile of 100 genes encoding for ECM proteins at 1, 8 and 45 days post-injury, in the spinal cord segments rostral and caudal to the lesion and in the scar segment, in a rat model. During both the active lesion phases and the lesion stabilization, we observed an asymmetric gene expression induced by the injury, with a higher regulation in the rostral segment of genes involved in ECM remodeling, adhesion and cell migration. Using bioinformatic approaches, the metalloproteases inhibitor Timp1 and the hyaluronan receptor Cd44 emerged as the hub genes at all post-lesion times. Results from the bioinformatic gene expression analysis were then confirmed at protein level by tissue analysis and by cell culture using primary astrocytes. These results indicated that ECM regulation also takes place outside of the lesion area in spinal cord injury.

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Section: Discussionsupporting

confidence: 70%

Time-Course Changes of Extracellular Matrix Encoding Genes Expression Level in the Spinal Cord Following Contusion Injury—A Data-Driven Approach

Bighinati

Khalajzeyqami

Baldassarro

et al. 2021

IJMS

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“…The biomarkers profile, observed in the CSF, collected within 24 h from the injury, also reflects inflammation as the prevalent pathogenic mechanism at this stage of this progressive pathology, that will chronically evolve in neurodegeneration and demyelination. Inflammation is a major player in the so-called "secondary degeneration", that expands the initial damage, sustaining the chronic evolution of the lesion [35], and a recognized, effective target for early pharmacological intervention [36,37]. However, being the traumatic lesion itself, such as the tissue and systemic reaction, a highly personalized process, appropriate biomarker discovery strategy should be based on serial sampling of biological fluids, from injury to stabilization.…”

Section: Discussionmentioning

confidence: 99%

Early CSF Biomarkers and Late Functional Outcomes in Spinal Cord Injury. A Pilot Study

Capirossi¹,

Piunti²,

Fernández

et al. 2020

IJMS

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Although, biomarkers are regarded as an important tool for monitoring injury severity and treatment efficacy, and for predicting clinical evolution in many neurological diseases and disorders including spinal cord injury, there is still a lack of reliable biomarkers for the assessment of clinical course and patient outcome. In this study, a biological dataset of 60 cytokines/chemokines, growth factorsm and intracellular and extracellular matrix proteins, analyzed in CSF within 24 h of injury, was used for correlation analysis with the clinical dataset of the same patients. A heat map was generated of positive and negative correlations between biomarkers and clinical rating scale scores at discharge, and between biomarkers and changes in clinical scores during the observation period. Using very stringent statistical criteria, we found 10 molecules which correlated with clinical scores at discharge, and five molecules, which correlated with changes in clinical scores. The proposed methodology may be useful for generating hypotheses regarding “predictive” and “treatment effectiveness” biomarkers, thereby suggesting potential candidates for disease-modifying therapies using a “bed-to-bench” approach.

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“…Bighinati et al designed an implantable biomaterial containing ibuprofen and T3 that provided longterm release of T3 at the lesion site. The local delivery of T3 by the implantable biomaterial facilitated the maturation of myelinating oligodendrocytes and remyelination in the injured spinal cord, and reduced the spontaneous release of glutamate, which was excitotoxic to neurons (Bighinati et al, 2020). Therefore, a treatment combining T3 with biological materials potentially represents a promising therapy in future studies.…”

Section: Biological Materials Implanted With Ths For Appropriate Drugmentioning

confidence: 99%

“…Secondary injury is characterized as chronic damage caused by several pathological changes after injury, leading to the activation of the inflammatory response, oxidative stress, apoptosis, and necrosis of neurons (Zhou et al, 2019; Figure 1). Mechanistically, secondary injury induces the release of a cascade of neurotoxic factors in the lesion site, which not only aggravate the inflammatory response and cell death of damaged neurons but also elicit the formation of a glial scar, demyelination and axon degeneration, contributing to the deteriorating clinical outcome (Bighinati et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Endocrine Therapy for the Functional Recovery of Spinal Cord Injury

et al. 2020

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Spinal cord injury (SCI) is a major cause of physical disability and leads to patient dissatisfaction with their quality of life. Patients with SCI usually exhibit severe clinical symptoms, including sensory and motor dysfunction below the injured levels, paraplegia, quadriplegia and urinary retention, which can exacerbate the substantial medical and social burdens. The major pathological change observed in SCI is inflammatory reaction, which induces demyelination, axonal degeneration, and the apoptosis and necrosis of neurons. Traditional medical treatments are mainly focused on the recovery of motor function and prevention of complications. To date, numerous studies have been conducted to explore the cellular and molecular mechanism of SCI and have proposed lots of effective treatments, but the clinical applications are still limited due to the complex pathogenesis and poor prognosis after SCI. Endocrine hormones are kinds of molecules that are synthesized by specialized endocrine organs and can participate in the regulation of multiple physiological activities, and their protective effects on several disorders have been widely discussed. In addition, many studies have identified that endocrine hormones can promote nerve regeneration and functional recovery in individuals with central nervous system diseases. Therefore, studies investigating the clinical applications of endocrine hormones as treatments for SCI are necessary. In this review, we described the neuroprotective roles of several endocrine hormones in SCI; endocrine hormone administration reduces cell death and promotes functional repair after SCI. We also proposed novel therapies for SCI.

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Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System

Cited by 17 publications

References 55 publications

Time-Course Changes of Extracellular Matrix Encoding Genes Expression Level in the Spinal Cord Following Contusion Injury—A Data-Driven Approach

Time-Course Changes of Extracellular Matrix Encoding Genes Expression Level in the Spinal Cord Following Contusion Injury—A Data-Driven Approach

Early CSF Biomarkers and Late Functional Outcomes in Spinal Cord Injury. A Pilot Study

Endocrine Therapy for the Functional Recovery of Spinal Cord Injury

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