Spinal Cord Injury Causes Sustained Disruption of the Blood-Testis Barrier in the Rat

Abstract

There is a high incidence of infertility in males following traumatic spinal cord injury (SCI). Quality of semen is frequently poor in these patients, but the pathophysiological mechanism(s) causing this are not known. Blood-testis barrier (BTB) integrity following SCI has not previously been examined. The objective of this study was to characterize the effects of spinal contusion injury on the BTB in the rat. 63 adult, male Sprague Dawley rats received SCI (n = 28), laminectomy only (n = 7) or served as uninjured, age-matched controls (n = 28). Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), BTB permeability to the vascular contrast agent gadopentate dimeglumine (Gd) was assessed at either 72 hours-, or 10 months post-SCI. DCE-MRI data revealed that BTB permeability to Gd was greater than controls at both 72 h and 10 mo post-SCI. Histological evaluation of testis tissue showed increased BTB permeability to immunoglobulin G at both 72 hours- and 10 months post-SCI, compared to age-matched sham-operated and uninjured controls. Tight junctional integrity within the seminiferous epithelium was assessed; at 72 hours post-SCI, decreased expression of the tight junction protein occludin was observed. Presence of inflammation in the testes was also examined. High expression of the proinflammatory cytokine interleukin-1 beta was detected in testis tissue. CD68+ immune cell infiltrate and mast cells were also detected within the seminiferous epithelium of both acute and chronic SCI groups but not in controls. In addition, extensive germ cell apoptosis was observed at 72 h post-SCI. Based on these results, we conclude that SCI is followed by compromised BTB integrity by as early as 72 hours post-injury in rats and is accompanied by a substantial immune response within the testis. Furthermore, our results indicate that the BTB remains compromised and testis immune cell infiltration persists for months after the initial injury.

Licofelone Modulates Neuroinflammation and Attenuates Mechanical Hypersensitivity in the Chronic Phase of Spinal Cord Injury

“…Animals received a laminectomy at spinal cord thoracic level 10 (T10), and the vertebral column was stabilized at T9 and T11. A moderate contusion injury (150 kdynes of force with 1 s dwell) was delivered to the spinal cord at T10 using the Infinite Horizon Impactor (Precision Systems and Instrumentation, LLC, Fairfax Station, VA), without opening the dura mater (Scheff et al, 2003; Dulin et al, 2011). The overlying muscles were immediately sutured and the skin was closed with stainless steel wound clips.…”

Sertoli cells – Immunological sentinels of spermatogenesis

“…The inflammatory response after SCI has been associated with tight junction disruption within the uroepithelium of the bladder. In an attempt to investigate whether the higher incidence of male infertility following traumatic SCI could be attributed to disruption of the BTB/SC barrier caused by SCI-associated inflammatory response, the integrity of the BTB/SC barrier and autoimmune response after SCI in rats was explored [34]. Increased permeability of the BTB/SC barrier to the small molecular weight molecule, gadopentate dimeglumine, following acute (72hrs) and chronic (10 month) SCI in adult rats indicated that the integrity of the BTB/SC barrier was breached.…”

“…Increased permeability of the BTB/SC barrier to the small molecular weight molecule, gadopentate dimeglumine, following acute (72hrs) and chronic (10 month) SCI in adult rats indicated that the integrity of the BTB/SC barrier was breached. Furthermore, increased antibody deposition, immune cell (mast cells and macrophages) infiltration within the testicular interstitium and seminiferous tubules and germ cell apoptosis in SCI rat testes was observed [34]. Collectively, the BTB/SC barrier creates a conducive environment necessary for completion of spermatogenesis and sequestering the auto-immunogenic germ cells from the immune system.…”

The Dual Cyclooxygenase/5-Lipoxygenase Inhibitor Licofelone Attenuates P-Glycoprotein-Mediated Drug Resistance in the Injured Spinal Cord

“…76 SCI surgeries were performed as previously described. 77,78 Incisions were made on the animals' dorsal skin and overlying muscles and the vertebral column was exposed. A laminectomy was performed at thoracic level 10 (T10) and the vertebral column was stabilized using forceps that grasp the ventral surface of the lateral spinous processes at vertebral levels T9 and T11.…”

“…The primary reason for the use of male rats in the latter studies is our emerging interest on the impact of SCI on the blood-testis barrier, 77 causing our laboratory to switch to the use of male rats during the course of this study. Although previous studies have indicated that there are gender-associated differences in Pgp transport activity in body tissues of experimental animals and humans, 110 we have not yet investigated whether there is a differential impact of SCI on Pgp expression and/or function in male and female rats.…”