Hormonal And Immunological Changes in Mice after Spinal Cord Injury

Abstract

Spinal cord injury (SCI) is associated with immune deficiencies and life-threatening infections. However, the specific mechanisms underlying this pathological condition remain unclear. In recent years, increasing evidence has suggested that anabolic hormones may be involved in immunological complications. Here, we monitored candidate hormone concentrations and immune cell counts, in CD1 mice, for 4 weeks after low-thoracic transection of the spinal cord (Tx). Serum dihydroepiandrosterone (DHEA), insulin, and parathyroid hormone (PTH) levels decreased throughout the time period studied compared with control, non-Tx mice. In turn, testosterone and growth hormone (GH) levels were only transiently changed, with a decrease of testosterone during the first 2 weeks and an increase of GH at 1 week post-Tx. A complete blood count revealed either unchanged or moderately decreased erythrocyte, platelet, hemoglobin and hematocrit levels. Total leukocyte, lymphocyte, and eosinophil counts also decreased, whereas neutrophils and monocytes did not change significantly. In the bone marrow, lymphocyte numbers decreased and neutrophils increased, whereas monocytes, eosinophils, and megakariocytes did not change significantly. These results revealed significant changes occurring rapidly (<1-2 weeks) after Tx in both hormonal and immunological systems, providing compelling evidence of a role for anabolic hormones in SCI-related immune deficiencies.

Early adaptive changes in chronic paraplegic mice: a model to study rapid health degradation after spinal cord injury

“…We found early transient changes in testosterone (decreased) and GH (increased) levels during the first 2 weeks post-Tx. 8 In contrast, DHEA, PTH and insulin levels were reduced throughout the time period studied. Specifically, levels of testosterone in Tx mice were reduced by 40 and 50% at 1 and 2 weeks post-Tx, respectively.…”

“…[5][6][7][8] All experimental procedures were conducted in accordance with the Canadian Council for Animal Care guidelines and accepted by the Laval University Animal Care, Use and Ethics Committee. In brief, adult male CD1 mice (Charles River Canada, St Constant, Quebec) weighing 30-40 g were used.…”

“…A complete blood count revealed unchanged or moderately decreased erythrocyte, platelet, hemoglobin and hematocrit levels. 8 In contrast, leukocyte counts were greatly reduced in Tx mice compared with controls. Total leukocyte numbers decreased by 35% (P ¼ 0.002) at 1 week post-Tx and remained low at 2, 3 and 4 weeks (Po0.05).…”

“…We found a general decrease in lymphocytes and mixed changes in neutrophils, monocytes and megakaryocytes after Tx. 8 These results can be compared, to some extent, with those from SCI patients where reduced lymphocyte levels (specifically lymphocytes-T and NK cells) were found at 3 months post-SCI, 23 which may perhaps contribute to the state of immune deficiency found generally in SCI patients.…”

Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

“…Testosterone in males is physiologically secreted by the testes and adrenal glands, and acts primarily via androgen receptors. Data suggests that testosterone levels are reduced in male patients and animals after SCI, especially in the acute period (Clark et al, 2008;Rouleau et al, 2007;Schopp et al, 2006). There is some evidence that testosterone is protective against central nervous system (CNS) damage such as neurodegenerative diseases (Bialek et al, 2004;Gold and Voskuhl, 2006;Hammond et al, 2001) and oxidative stress (Chisu et al, 2006).…”