CD44 Knockout Alters the Cellular Response and Improves Locomotor Outcome After Spinal Cord Injury

Spinal cord injury (SCI) is a devastating condition that results in long-term functional impairments due to loss of tissue and limited regeneration. Investigating the factors that regulate the post-SCI response is critical to understanding the pathophysiology of this condition and developing treatments. One molecule of interest in the post-SCI response is CD44. CD44 is cell-surface protein with a well-established role in regulating cellular functions including cell migration and proliferation. CD44 is expressed in many cells that play a role in the post-SCI microenvironment but the effect of global CD44 KO on SCI outcomes has not previously been tested. Here, we investigate that role in a mouse unilateral cervical contusion SCI model. We predicted that CD44 KO would exert a predominant effect on glial progenitor/cell recruitment, inhibiting astroglial scar formation and thereby increasing lesion expansion and exacerbating locomotor deficits. In contrast, we found that CD44 KO mice exhibited increased numbers of astrocytes at the lesion epicenter, developed a more compact astroglial scar by 28 days after injury, showed improved locomotor function, and exhibited decreased recruitment of acutely activated immune cells vs WT mice. Together, these findings highlight the role of CD44 in diverse cell populations after SCI as a critical point of further investigation to understand the post-SCI response.