Glibenclamide treatment improved intraspinal blood volume, tissue sparing, and functional recovery after cervical spinal cord injury in rats.

Limiting the expansion of the primary injury after a traumatic spinal cord injury (SCI) can offer improved functional outcomes. Glibenclamide (glyburide) has been shown to limit intraspinal bleeding and promote vascular stability after SCI in rats, but its impact on intraspinal hemodynamics has not been investigated. Here, we hypothesized that acute glibenclamide treatment would improve intraspinal hemodynamics after a cervical contusion SCI in a rat model (200 kdyn). Intravital ultrafast contrast enhanced ultrasound (CEUS) imaging revealed that glibenclamide treatment significantly increased total blood volume (i.e., tissue perfusion) at 72-hours post-injury (hpi) compared to vehicle treated controls (p<0.05, Cohen's d >1.2). Histological data confirmed that glibenclamide treatment significantly lowered caspase-8-positive cells in the white matter at 72-hpi (p<0.05, Cohen's d>1.2). Weekly forelimb locomotor scoring revealed significant functional improvements in animals treated with glibenclamide at 4-weeks post injury (wpi) (p<0.001, Cohen's d>1.2), which continued through to 8-wpi compared to vehicle treated animals (p<0.05, Cohen's d>1.2). Glibenclamide intervention significantly reduced lesion size by 8-wpi compared to controls (p<0.05; Cohen's d>1.2). This study is the first to report in vivo improvements in intraspinal blood volume associated with glibenclamide treatment after acute cervical SCI in rats.