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

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.

Bioactive role of vitamins as a key modulator of oxidative stress, cellular damage and comorbidities associated with spinal cord injury (SCI).

Introduction: Spinal cord injury (SCI) cause significant disability and impact the quality of life of those affected by it. The nutritional status and diet are fundamental to diminish the progression of complications; vitamins modulate the inflammatory response and oxidative stress, promote blood-spinal cord barrier preservation and the prompt recovery of homeostasis. A deep knowledge of the benefits achieved from vitamins in patients with SCI are summarized. Information of dosage, time, and effects of vitamins in these patients are also displayed. Vitamins have been extensively investigated; however, more clinical trials are needed to clarify the scope of vitamin supplementation.Objective: The objective of this review was to offer relevant therapeutic information based on vitamins supplementation for SCI patients.Methods: Basic and clinical studies that have implemented the use of vitamins in SCI were considered. They were selected from the year 2000-2022 from three databases: PubMed, Science Direct and Google Scholar.Results: Consistent benefits in clinical trials were shown in those who were supplemented with vitamin D (prevents osteoporosis and improves physical performance variables), B3 (improves lipid profile) and B12 (neurological prophylaxis of chronic SCI damage) mainly. On the other hand, improvement related to neuroprotection, damage modulation (vitamin A) and its prophylaxis were associated to B complex vitamins supplementation; the studies who reported positive results are displayed in this review.Discussion: Physicians should become familiar with relevant information that can support conventional treatment in patients with SCI, such as the use of vitamins, a viable option that can improve outcomes in patients with this condition.

Gonadotropin-Releasing Hormone Receptor Expression in Human Spinal Cord.

The expression of the gonadotrophin-releasing hormone receptor expression on pituitary gonadotrophs in humans is well characterized. In nervous system they have also been found in hippocampi and cerebral cortex. However, gonadotrophin-releasing hormone receptor expression in human spinal cord has not been reported. This study was to analyze the gonadotrophin-releasing hormone receptor expression in human spinal cord by immunohistochemistry, mRNAs by reverse transcriptase polymerase chain reaction, cDNA cloning and Western blot. The results show immunoreactive material to gonadotrophin-releasing hormone receptor in motoneurons of the spinal cord. Further, the study revealed that spinal cord expressed the gonadotrophin-releasing hormone receptor mRNA. The amplicon sequence corresponds to 100% of identity to GenBank. In Western blot, a band of 37 kDa were found in extracts of spinal cord and placenta as a control. In conclusion, human spinal cord expresses gonadotrophin-releasing hormone receptor analyzed through immunohistochemistry, the expression of its mRNA, cloning its cDNA and Western blot analysis. The presence of gonadotrophin-releasing hormone receptor in the spinal cord suggests the possibility of an extrapituitary functional role independent of reproductive system.

Neurological improvement in patients with chronic spinal cord injury treated with leuprolide acetate, an agonist of GnRH.

It has been reported that gonadotropin­releasing hormone (GnRH), and its analogue leuprolide acetate (LA), have neurotrophic properties; particularly in the regeneration of injured spinal cord in animal models and in the case of a patient with spinal cord injury (SCI). The aim of this study was to establish whether treatment with LA improves sensitivity, motor activity and independence in patients with chronic SCI. Patients were treated LA once a month for six months. They were evaluated at the beginning and at the end of treatment; using a sensitivity and motor impairment scale, according to the American Spinal Injury Association (ASIA), and grade of independence scale; employing the spinal cord independence measure (SCIM). Statistical analysis showed a significant improvement in the ASIA sensory score and the SCIM score when comparing the initial versus final evaluation after six months of LA administration. Some patients showed an increase in frequency of bowel movements. Treatment with LA induces improvements in sensitivity, motor activity and independence in patients with chronic SCI. One advantage of this protocol is that it is a non-invasive method of easy and safe application, with few side effects.

Leuprolide acetate induces structural and functional recovery of injured spinal cord in rats.

Gonadotropin-releasing hormone (GnRH) and its synthetic analog leuprolide acetate, a GnRH agonist, have neurotrophic properties. This study was designed to determine whether administration of leuprolide acetate can improve locomotor behavior, gait, micturition reflex, spinal cord morphology and the amount of microglia in the lesion epicenter after spinal cord injury in rats. Rats with spinal cord compression injury were administered leuprolide acetate or saline solution for 5 weeks. At the 5(th) week, leuprolide acetate-treated rats showed locomotor activity recovery by 38%, had improvement in kinematic gait and exhibited voiding reflex recovery by 60%, as compared with the 1(st) week. By contrast, saline solution-treated rats showed locomotor activity recovery only by 7%, but voiding reflex did not recover. More importantly, leuprolide acetate treatment reduced microglial immunological reaction and induced a trend towards greater area of white and gray matter in the spinal cord. Therefore, leuprolide acetate has great potential to repair spinal cord injury.