Neuroprotective Effects of N-Acetyl-Cysteine and Acetyl-L-Carnitine after Spinal Cord Injury in Adult Rats

Abstract

Following the initial acute stage of spinal cord injury, a cascade of cellular and inflammatory responses will lead to progressive secondary damage of the nerve tissue surrounding the primary injury site. The degeneration is manifested by loss of neurons and glial cells, demyelination and cyst formation. Injury to the mammalian spinal cord results in nearly complete failure of the severed axons to regenerate. We have previously demonstrated that the antioxidants N-acetyl-cysteine (NAC) and acetyl-L-carnitine (ALC) can attenuate retrograde neuronal degeneration after peripheral nerve and ventral root injury. The present study evaluates the effects of NAC and ALC on neuronal survival, axonal sprouting and glial cell reactions after spinal cord injury in adult rats. Tibial motoneurons in the spinal cord were pre-labeled with fluorescent tracer Fast Blue one week before lumbar L5 hemisection. Continuous intrathecal infusion of NAC (2.4 mg/day) or ALC (0.9 mg/day) was initiated immediately after spinal injury using Alzet 2002 osmotic minipumps. Neuroprotective effects of treatment were assessed by counting surviving motoneurons and by using quantitative immunohistochemistry and Western blotting for neuronal and glial cell markers 4 weeks after hemisection. Spinal cord injury induced significant loss of tibial motoneurons in L4–L6 segments. Neuronal degeneration was associated with decreased immunostaining for microtubular-associated protein-2 (MAP2) in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker GFAP and microglial marker OX42 was increased. Treatment with NAC and ALC rescued approximately half of the motoneurons destined to die. In addition, antioxidants restored MAP2 and synaptophysin immunoreactivity. However, the perineuronal synaptophysin labeling was not recovered. Although both treatments promoted axonal sprouting, there was no effect on reactive astrocytes. In contrast, the microglial reaction was significantly attenuated. The results indicate a therapeutic potential for NAC and ALC in the early treatment of traumatic spinal cord injury.

The neuroprotective effect of N-acetylcysteine in spinal cord-injured rats

“…They showed that both substances restored the density of dendritic branches and axons in the ventral horn of hemisected rat spinal cords. 22 However, Kaynar et al reported that a single dose of NAC administered intraperitoneally was ineffective after experimental spinal cord injury with an aneurysm clip in rats. 23 Naziroglu et al examined the effects of NAC and selenium on apoptosis and oxidative stress in the hippocampus of rats following brain injury.…”

Thymoquinone Attenuates Trauma Induced Spinal Cord Damage in an Animal Model

“…[16,17] A variety of known antioxidants and anti-inflammatory agents have shown protective effects on traumatic SCI in experimental models and clinical trials. [18][19][20][21][22][23][24] Toklu et al [18] have found that alpha-lipoic acid reduces oxidative stress on traumatic SCI. Sahin et al [19] have shown significant protective effects of curcumin on traumatic spinal cord tissues against oxidative damage.…”

“…Sahin et al [19] have shown significant protective effects of curcumin on traumatic spinal cord tissues against oxidative damage. Karalija et al [20] have demonstrated better pathological findings by Nacetyl-cysteine and acetyl-L-carnitine in the early treatment of traumatic SCI by using quantitative immunohistochemistry and western blotting for neuronal and glial cell markers, and indicated a therapeutic potential for NAC and ALC in the early treatment of traumatic SCI. Cemil B et al [21] have put forward better pathological findings by aged garlic extract in the traumatic SCI against oxidative damage.…”

Mitochondrial-Based Therapeutics for the Treatment of Spinal Cord Injury: Mitochondrial Biogenesis as a Potential Pharmacological Target

“…ALC also increases the production of glutathione (GSH), giving it a bipartite effect and further increasing its therapeutic appeal (Pettegrew et al, 2000;Karalija et al, 2012). ALC is shown to have beneficial effects for a number of neurodegenerative diseases, including Parkinson disease, Alzheimer disease, and multiple sclerosis (Puca et al, 1990;Pettegrew et al, 2000;Tomassini et al, 2004).…”