Effects of Cyclosporin-A, Minocycline, and Tacrolimus (FK506) on Enhanced Behavioral and Biochemical Recovery from Spinal Cord Injury in Rats

Abstract

Spinal cord injury (SCI) results into an immediate primary injury (physical damages) followed by secondary damages (prolonged posttraumatic inflammatory disorder) resulting into severe motor dysfunction including paralysis. The present chapter discusses and investigates the neuroprotective effects of cyclosporin-A (CsA), minocycline, and tacrolimus (FK506) and their therapeutic effectiveness in recovery from the animal model of SCI. Based on the available recent literature on these three drugs, as well as in perspective of the results obtained on some experimental behavioral, biochemical, and oxidative stress parameters in the present study, the therapeutical potential of these three drugs has been discussed. Furthermore, the animal model of SCI used herein has been reviewed and compared with other reported animal models for understanding the utility, suitability, and reproducibility of the methodology of the present model for screening purposes in quest of searching ideal therapeutic compounds for maximum recovery from SCI.

Antibiotics with therapeutic effects on spinal cord injury: a review

“…It can cross the brain–blood barrier and exert robust neuroprotective and neuroregenerative effects in different CNS diseases such as SCI ( Table 1 ) [1,89–95]. Tacrolimus promotes neuroprotection in addition to neural and axonal regeneration associated with functional recovery in SCI rodents [96–100]. This effect is mediated by inhibiting calcineurin [96–100], increasing neuronal growth‐associated protein (GAP)‐43 levels [91], inhibiting iNOS and superoxide radicals, preventing mitochondrial dysfunction and neuronal apoptosis signaling [101–103], inhibiting caspase 3 activity, and finally attenuating oligodendroglia apoptosis ( Figure ) [104].…”

“…Tacrolimus promotes neuroprotection in addition to neural and axonal regeneration associated with functional recovery in SCI rodents [96–100]. This effect is mediated by inhibiting calcineurin [96–100], increasing neuronal growth‐associated protein (GAP)‐43 levels [91], inhibiting iNOS and superoxide radicals, preventing mitochondrial dysfunction and neuronal apoptosis signaling [101–103], inhibiting caspase 3 activity, and finally attenuating oligodendroglia apoptosis ( Figure ) [104]. Other mechanisms underlying such effects of tacrolimus on SCI include attenuating invasion of pro‐inflammatory cells (e.g., macrophages) into the injured sites [105], decreasing glial fibrillary acidic protein (GFAP), COX‐2, and pro‐inflammatory cytokines (e.g., IL‐1β) levels [101], as well as inhibiting nuclear factor kappa B (NF‐kB) activation in microglia [90,93].…”