Stage I Out-of-the-Box Award Winner: Raymond Grill


Summary:

Spinal cord injury (SCI) produces a significant loss of fertility in males.  This is characterized by a significant reduction in sperm production in the testes with remaining sperm exhibiting aberrant functional properties.  Unfortunately, the pathological mechanisms underlying the loss of male fertility remain poorly understood.  As a result, men who live with an SCI experience a loss of one of our most primal biological functions, procreation.  We recently published a study that describes a loss of blood-testis-barrier (BTB) integrity within the testis of rats after SCI.  The BTB is a specialized structure found within the testis that protects the compartments where sperm cells are generated and mature.  SCI induces an early, but sustained, failure of the BTB that can be detected out to 10 months post-SCI.  Loss of BTB integrity can open the testis to attack from the immune system, leading to the production of auto-antibodies against one’s own sperm.   We subsequently found that SCI creates and sustains a profound state of inflammation and oxidative stress within the testes; detectable early but found to be present as late as 90 days post-insult.  We hypothesize that this pathological environment supports/maintains infertility from early-to-chronic time periods post-SCI.  Recently, we observed that acute treatment with licofelone, a novel dual inhibitor of cyclooxygenase and 5-lipoxygenase, produced an immediate and significant suppression of SCI-induced inflammation and oxidative stress within the testes.  In addition, rats with an SCI followed by 14 days of oral licofelone treatment showed a sustained reduction of these pathological conditions when examined 90 days after SCI.  Based on these results, we currently wish to determine whether DELAYED treatment with licofelone, initiated 90 days after insult, can suppress inflammation and oxidative stress and improve sperm integrity in a chronic rat SCI model.  If successful, this would represent a novel, effective means of restoring fertility to males living with chronic SCI.

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