Acute baclofen administration promotes functional recovery after spinal cord injury

Sousa, Nídia de; Pinho, Andreia G.; Monteiro, Susana; Liberato, Valentina; Santos, Diogo J; Campos, Jonas; Cibrão, Jorge R.; Silva, Nuno; Barreiro‐Iglesias, Antón; Salgado, António J.

doi:10.1016/j.spinee.2022.09.007

Cited by 7 publications

(10 citation statements)

References 28 publications

(33 reference statements)

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“…[ 2 , 3 ] showed that baclofen (a GABAB receptor agonist) administration inhibits caspase activation and promotes axon regeneration in descending neurons of lampreys after a complete SCI. More recently, our group also showed that an acute baclofen treatment (starting on the day of injury) improves locomotor recovery and control of bladder function after SCI in mice [1] . Importantly, this correlates well with observational data in human patients revealing a positive association between baclofen administration and neurological recovery after SCI [ 4 , 5 ].…”

Section: Objectivementioning

confidence: 86%

“…During post-operative care, animals were also monitored for body temperature and recovery of general activities. Basso Mouse Scale (BMS) was used 48 h post-injury (hpi) as previously described [1] to confirm the SCI led to no motor movement in both hind paws (BMS score = 0). BMS scoring was performed as a quality control procedure for the surgery to exclude eventual partial lesions.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…Here, we used one of the baclofen treatment conditions (1 mg/kg administrated intraperitoneally once a day) previously used by de Sousa et al. [1] and performed an RNA-seq analysis of the spinal cord of control and baclofen treated mice 7 days after a T10-T11 compression SCI.…”

Section: Objectivementioning

confidence: 99%

“…Currently, there are no available pharmacological treatments to promote neurological recovery in SCI patients. Recent work from our group has shown that a baclofen treatment can promote functional recovery after a compression SCI in mice [1] . Here, we provide transcriptomic (RNA-seq) data from adult mouse spinal cords collected 7 days after a compression SCI and baclofen (vs vehicle) administration.…”

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confidence: 99%

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Spinal cord RNA-seq data after a baclofen treatment in mice with a spinal cord injury

et al. 2023

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Section: Objectivementioning

confidence: 86%

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Section: Objectivementioning

confidence: 99%

mentioning

confidence: 99%

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Spinal cord RNA-seq data after a baclofen treatment in mice with a spinal cord injury

et al. 2023

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“…The Von Frey test was used to determine tactile sensitivity by measuring how much force is required to elicit movement of the paw fingers, using the up-and-down method with Von Frey monofilaments, as previously described ( 26 ). The experimental setting consisted of placing the mice in an elevated mesh restrained inside a standard perforated box.…”

Section: Methodsmentioning

confidence: 99%

The secretome of macrophages has a differential impact on spinal cord injury recovery according to the polarization protocol

Lentilhas-Graça,

Santos,

Afonso

et al. 2024

Front. Immunol.

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IntroductionThe inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed.MethodsIn this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues.ResultsWe demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL-10 and TGF-β1 (M(IL-10+TGF-β1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-β1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-β1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-β1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation.DiscussionOverall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications.

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Effects of two external cooling strategies on physiological and perceptual responses of athletes with tetraplegia during and after exercise in the heat

Lôbo,

Wanner,

Guerreiro

et al. 2024

Journal of Thermal Biology

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Acute baclofen administration promotes functional recovery after spinal cord injury

Cited by 7 publications

References 28 publications

Spinal cord RNA-seq data after a baclofen treatment in mice with a spinal cord injury

Spinal cord RNA-seq data after a baclofen treatment in mice with a spinal cord injury

The secretome of macrophages has a differential impact on spinal cord injury recovery according to the polarization protocol

Effects of two external cooling strategies on physiological and perceptual responses of athletes with tetraplegia during and after exercise in the heat

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