Clinic‐ready inhibitor of MMP‐9/‐12 restores sensory and functional decline in rodent models of spinal cord injury.

Since the rat DC injury model better recapitulates human SCI pathophysiology,1,5 the same profile of MMP-9 (Figure S10A) and MMP-12 (Figure S10B) mRNA expression was also observed. (D) Inhibition of MMP-9 and MMP-12 by oral AZD1236 attenuates mRNA levels of proinflammatory pain markers interleukin-1 (IL-1 ), tumour necrosis factor- (TNF- ) and interleukin-6 (IL-6) in the DC injury model. This study demonstrated that short-term inhibition of matrix metalloprotease (MMP)-9 and MMP-12 in both mouse and rat models of spinal cord injury (SCI) using the clinic-ready, orally bioavailable and specific inhibitor, AZD1236, attenuated injury-induced oedema, proinflammatory pain markers, pain sensation and blood-spinal cord barrier (BSCB) breakdown. (E) Inhibition of MMP-9 and MMP-12 by intrathecal AZD1236 also attenuates mRNA levels of proinflammatory pain markers IL-1 , TNF- and IL-6 in the DC injury model. [Extracted from the article]