Neuroprotective Effects of the Pannexin-1 Channel Inhibitor: Probenecid on Spinal Cord Injury in Rats

Abstract

Proinflammatory immune cell subsets constitute the majority in the local microenvironment after spinal cord injury (SCI), leading to secondary pathological injury. Previous studies have demonstrated that inflammasomes act as an important part of the inflammatory process after SCI. Probenecid, an inhibitor of the Pannexin-1 channel, can inhibit the activation of inflammasomes. This article focuses on the effects of probenecid on the local immune microenvironment, histopathology, and behavior of SCI. Our data show that probenecid inhibited the expression and activation of nucleotide-binding oligomerization domain receptor pyrindomain-containing 1 (NLRP1), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1, interleukin-1β (IL-1β), and caspase-3 proteins associated with inflammasomes, thereby suppressing the proportion of M1 cells. And consequently, probenecid reduced the lesion area and demyelination in SCI. Moreover, the drug increased the survival of motor neurons, which resulted in tissue repair and improved locomotor function in the injured SC. Altogether, existing studies indicated that probenecid can alleviate inflammation by blocking Pannexin-1 channels to inhibit the expression of caspase-1 and IL-1β, which in turn restores the balance of immune cell subsets and exerts neuroprotective effects in rats with SCI.

Serum levels of neurotensin, pannexin-1, and sestrin-2 and the correlations with sleep quality or/and cognitive function in the patients with chronic insomnia disorder

“…Up-regulation of pannexin-1 expression has been demonstrated to exert an essential influence in multiple brain injury diseases such as epilepsy ( 51 ), sepsis-associated encephalopathy ( 52 ), and subarachnoid hemorrhage ( 53 ). Pannexin-1 channel inhibitor can improve neurological dysfunction and exert neuroprotective effects by means of reducing inflammasomes activation ( 54 ). In line with the results in human traumatic brain injury, serum pannexin-1 concentrations increases after intracerebral hemorrhage, hinting that serum pannexin-1 may be at least partially originated from central nervous system ( 55 ).…”

Pharmacological Screening of Anti-arthritic Effect of Biological Synthesis ZnONPs by Syzygium aromaticum in Rats

“…Interleukin 10 (IL-10) is an immunoregulatory cytokine produced by Treg cells that is important in the prevention of tissue damage caused by inflammation (Li et al, 2023). The production of this substance is predominantly attributed to monocytes/macrophages, and it exerts a significant anti-inflammatory influence on the activities of T-lymphocytes and monocytes.…”

Role of dendritic cells in spinal cord injury

“…46 However, IL-10 is believed to inhibit early inflammation after SCI by preventing the activation of pro-inflammatory cells. 47 In summary, ILs are critical in regulating the immune system and responding to inflammation in SCI. A better understanding of their functions can help us comprehend the mechanisms underlying SCI, leading to effective treatments.…”

“…All of which accelerates the activation of inflammatory cells 46 . However, IL‐10 is believed to inhibit early inflammation after SCI by preventing the activation of pro‐inflammatory cells 47 . In summary, ILs are critical in regulating the immune system and responding to inflammation in SCI.…”