Leuprolide Acetate, a GnRH Agonist, Improves the Neurogenic Bowel in Ovariectomized Rats with Spinal Cord Injury

Altamira‐Camacho, Moises; Medina-Aguiñaga, Daniel; Cruz, Yolanda; Calderón-Vallejo, Denisse; Kovács, K.; Rotondo, Fabio; Quintanar, J. Luis

doi:10.1007/s10620-019-05783-4

Cited by 8 publications

(3 citation statements)

References 26 publications

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“…In vitro experiments with culture of rat embryonic spinal cord neurons, it has been observed that incubation with GnRH induces a significant neuritic growth, as well as an increase in the expression of neurofilaments presenting a neurotrophic effect [5]. Likewise, the administration of LA improves the neurogenic bowel conditions caused by spinal cord injury in rats, indicating an effect on the peripheral nerve [6]. According to this background, it is possible that the treatment with LA induces a recovery in the peripheral nerves through the trophic effect on the neurofilaments, since these determine the axonal diameter and thus increase its conduction velocity.…”

Section: Discussionmentioning

confidence: 99%

"Electromyographic and Clinical Improvement in a Chronic Spinal Cord Injury Patient Treated with Leuprolide Acetate, a Case Report"

Quintanar¹

2022

BJSTR

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Patients with spinal cord injury (SCI) have central and peripheral nervous system damage and they exhibited an abnormal electromyography (EMG) response. Leuprolide acetate (LA) has been reported to induce neural regeneration after SCI in animal models and humans. The aim of this work was to analyze whether electromyography and clinical variables improved with treatment of LA in a patient with SCI. A 38-yearold woman had a car accident and a complete spinal cord section at C6 level was diagnosed. One year after the car accident, EMG and initial clinical evaluations were performed. Six months after these initial evaluations, treatment with LA started and consisted of an intramuscular injection (7.5 mg) each month during six months. At the end of this time, the electromyography and clinical signs were reevaluated. The patient treated with LA showed an increase nerve conduction velocity, encourage of muscle activity and higher muscle strength respect to initial evaluation. In conclusion, LA stimulate the recovery of muscle strength. These results are important because they offer an accessible pharmacological strategy that can improve the quality of life of patients with SCI.

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Section: Discussionmentioning

confidence: 99%

"Electromyographic and Clinical Improvement in a Chronic Spinal Cord Injury Patient Treated with Leuprolide Acetate, a Case Report"

Quintanar¹

2022

BJSTR

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“…Thus, it is important to develop novel neuroprotective or neuroregenerative treatments for mild HIE. Previously, it has been reported the effect of the leuprolide acetate (LA), an agonist of the gonadotropin releasing hormone (GnRH), as a neuroregenerative [8][9][10] and immunomodulator [11] in other nervous system injuries. The objective of this study was to evaluate the immunomodulatory effect of LA in the acute phase of mild HIE and its effects in motor and behavior in a subacute phase of the mild HIE.…”

Section: Introductionmentioning

confidence: 99%

Effect of Leuprolide Acetate, a GnRH Agonist, on Neuroinflammation and Anxiety-Like Behavior after Mild Hypoxic-Ischemic Encephalopathy in Rat Model

Pedroza-García,

Calderón-Vallejo,

Cervantes-García

et al. 2023

Neuroimmunomodulation

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Background: Mild hypoxic-ischemic encephalopathy (HIE) is a condition that predisposes to negative outcomes such as neuroanatomical injury, mood disorders, and motor or cognitive disabilities. The neuroinflammation plays an important role in the neurological damage; therefore, reducing it could provide neuroprotection. The leuprolide acetate (LA) has shown to have neuroregenerative and immunomodulator properties in other nervous system injuries. Objective: The aim of this study was to evaluate the immunomodulatory effect of LA in the acute phase of mild HIE and its effects in motor activity and behavior in a subacute phase. Method: Forty-five Wistar rats on postnatal day 7 were divided into Sham, HIE treated with saline solution (HIE-SS), and HIE-LA. The HIE was performed cutting of the right carotid artery followed by 60 min of hypoxia. The expression of the inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and the chemokine CXCL-1 were evaluated 72 h after HIE by RT-qPCR and the motor activity and behavior were evaluated by open field test at postnatal day 33. Results: HIE-SS animals showed increased expression of IL-1β, TNF-α, IFN-γ, and CXCL-1 genes in injured tissue. However, the HIE-LA group exhibited similar expression levels of IL-1β and TNF-α to the Sham group, while IFN-γ and CXCL-1 mRNA expression were attenuated with LA treatment. LA treatment also prevented anxiety-like behavior in the open field test. Conclusion: Treatment with LA partially reverses HIE-induced neuroinflammation and prevents anxiety-like behavior in neonatal rats.

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“…Moreover, chronic administration of GnRH or leuprolide acetate (LA)-a GnRH analog-for 5 weeks consistently improved urodynamic parameters and sensorimotor function in rats with SCI (Calderón-Vallejo and Quintanar, 2012;Calderón-Vallejo et al, 2015;Díaz Galindo et al, 2015). In humans, the presence of GnRH receptor (GnRHR) in spinal cord tissue has been confirmed and it is proposed that some of the beneficial actions observed in SCI rats and patients treated with LA are, at least, partially mediated through local GnRHR activation (Quintanar et al, 2018;Altamira-Camacho et al, 2020;Díaz-Galindo et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Gonadotropin-releasing hormone and growth hormone act as anti-inflammatory factors improving sensory recovery in female rats with thoracic spinal cord injury

et al. 2023

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The potential for novel applications of classical hormones, such as gonadotropin-releasing hormone (GnRH) and growth hormone (GH), to counteract neural harm is based on their demonstrated neurotrophic effects in both in vitro and in vivo experimental models and a growing number of clinical trials. This study aimed to investigate the effects of chronic administration of GnRH and/or GH on the expression of several proinflammatory and glial activity markers in damaged neural tissues, as well as on sensory recovery, in animals submitted to thoracic spinal cord injury (SCI). Additionally, the effect of a combined GnRH + GH treatment was examined in comparison with single hormone administration. Spinal cord damage was induced by compression using catheter insufflation at thoracic vertebrae 10 (T10), resulting in significant motor and sensory deficits in the hindlimbs. Following SCI, treatments (GnRH, 60 μg/kg/12 h, IM; GH, 150 μg/kg/24 h, SC; the combination of both; or vehicle) were administered during either 3 or 5 weeks, beginning 24 h after injury onset and ending 24 h before sample collection. Our results indicate that a chronic treatment with GH and/or GnRH significantly reduced the expression of proinflammatory (IL6, IL1B, and iNOS) and glial activity (Iba1, CD86, CD206, vimentin, and GFAP) markers in the spinal cord tissue and improved sensory recovery in the lesioned animals. Furthermore, we found that the caudal section of the spinal cord was particularly responsive to GnRH or GH treatment, as well as to their combination. These findings provide evidence of an anti-inflammatory and glial-modulatory effect of GnRH and GH in an experimental model of SCI and suggest that these hormones can modulate the response of microglia, astrocytes, and infiltrated immune cells in the spinal cord tissue following injury.

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Leuprolide Acetate, a GnRH Agonist, Improves the Neurogenic Bowel in Ovariectomized Rats with Spinal Cord Injury

Cited by 8 publications

References 26 publications

"Electromyographic and Clinical Improvement in a Chronic Spinal Cord Injury Patient Treated with Leuprolide Acetate, a Case Report"

"Electromyographic and Clinical Improvement in a Chronic Spinal Cord Injury Patient Treated with Leuprolide Acetate, a Case Report"

Effect of Leuprolide Acetate, a GnRH Agonist, on Neuroinflammation and Anxiety-Like Behavior after Mild Hypoxic-Ischemic Encephalopathy in Rat Model

Gonadotropin-releasing hormone and growth hormone act as anti-inflammatory factors improving sensory recovery in female rats with thoracic spinal cord injury

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