The Effects of Minocycline on Spinal Root Avulsion Injury in Rat Model

Abstract

Methods: The C7 nerve roots of the animals were avulsed via an anterior extravertebral approach. Traction force was used to transect the ventral motor nerve roots at the preganglionic level. Intraperitoneal and intrathecal minocycline (50 mg/kg for the first week and 25 mg/kg for the second week) were administered to promote motor healing. The spinal cord was harvested six weeks after the injury, and structural changes following the avulsion injury and pharmacological intervention were analysed.Results: Motor neuron death and microglial proliferation were observed after the administration of minocycline via two different routes (intraperitoneal and intrathecal) following traumatic avulsion injury of the ventral nerve root. The administration of intraperitoneal minocycline reduced the microglia count but increased the motor neuron count. Intrathecal minocycline also reduced the microglial count, with a greater reduction than in the intraperitoneal group, but it decreased the motor neuron count.Conclusions: Intraperitoneal minocycline increased motor neuron survival by inhibiting microglial proliferation following traumatic avulsion injury of the nerve root. The inhibitory effect was augmented by the use of intrathecal minocycline, in which the targeted drug delivery method increased the bioavailability of the therapeutic agent. However, motor neuron survival was impaired at a higher concentration of minocycline via the intrathecal route due to the more efficient method of drug delivery. Microglial suppression via minocycline can have both beneficial and damaging effects, with a moderate dose being beneficial as regards motor neuron survival but a higher dose proving neurotoxic due to impairment of the glial response and Wallerian degeneration, which is a pre-requisite for regeneration.

Nerve Root Reimplantation in Brachial Plexus Injuries

“…The timing of NR reimplantation is crucial, as a longer waiting period will correlate with a greater amount of MNs undergoing apoptosis [20,27,91,93,[101][102][103]. The percentage of dead MNs increases from 20% by 10-12 days post-avulsion [13,65,69] to 50% by 4 weeks [104,105], 85% by 6 weeks [106] and 90% by 20 weeks [27,83,93,107]. Early NR reimplantation seems to have neuroprotective effects [27,83,89,93,108,109], but some MN loss will happen even if repair occurs immediately after avulsion [93,101].…”

“…Minocycline can cross the blood-brain barrier and has anti-inflammatory properties [120]. In rats, it has been administered intraperitoneally and intrathecally, with better results through the latter route [106]. At low doses, minocycline has neuroprotective properties, but at high concentrations it is neurotoxic [164], among other reasons, because glial proliferation and Wallerian degeneration are a sine qua non for nerve regeneration [106].…”

“…For the dorsal root, CNTF [87] applied directly to the section of the posterior SC where the sensory rootlets get in combined with oral N-acetyl cysteine [155] allows maximal sensory neuron survival. Other agents could be added, such as oral minocycline [106,120], tacrolimus [151] or recombinant erythropoietin [118,165]to reduce the reactive glial proliferation that impairs the axonal regeneration. ISP should be administered subcutaneously to minimize astrocyte inhibition of axonal regeneration [126,167].…”

“…To improve the results, CNTF [87] should apply locally to the posterior SC at the DREZ associated with N-acetyl cysteine [155] orally to allow maximal sensory neuron survival. Oral minocycline [106,120], oral tacrolimus [151] or subcutaneous recombinant erythropoietin [118,165] could be also administered to reduce the reactive glial proliferation that acts as a barrier against dorsal root axonal regeneration.…”

Role of Soluble Fas Ligand in Severity of Dengue Disease

“…The recent study showed that soluble Fas ligand can be used as a potential marker of severity of dengue infection because the study showed that there was a significant increase in the soluble Fas ligand level in DHF patients compared to DF patients [33].…”