Administration of N‐acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke

Abstract

Free radicals and inflammatory mediators are involved in transient focal cerebral ischemia (FCI). Preadministration of N-acetylcysteine (NAC) has been found to attenuate the cerebral ischemia-reperfusion injury in a rat model of experimental stroke. This study was undertaken to investigate the neuroprotective potential of NAC administered after ischemic events in experimental stroke. FCI was induced for 30 min by occluding the middle cerebral artery (MCA). NAC (150 mg/kg) was administered intraperitoneally at the time of reperfusion followed by another dose 6 hr later. Animals were sacrificed after 24 hr of reperfusion. The cerebral infarct consistently involved the cortex and striatum. Infarction was assessed by staining the brain sections with 2,3,5-triphenyltetrazolium chloride. Animals treated with NAC showed a significant reduction in infarct area and infarct volume and an improvement in neurologic scores and glutathione level. Reduction in infarction was significant even when a single dose of NAC was administered at 6 hr of reperfusion. Immunohistochemical and quantitative real-time PCR studies demonstrated a reduction in the expression of proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta) and inducible nitric oxide synthase (iNOS) in NAC compared to that in vehicle-treated animals. The expression of activated macrophage/microglia (ED1) and apoptotic cell death in ischemic brain was also reduced by NAC treatment. These results indicate that in a rat model of experimental stroke, administration of NAC even after ischemia onset protected the brain from free radical injury, apoptosis, and inflammation, with a wide treatment window.

Lipopolysaccharide-induced peroxisomal dysfunction exacerbates cerebral white matter injury: Attenuation by N-acetyl cysteine

“…NAC is probably one of the most widely investigated agents that serves as a precursor of glutathione and has both antioxidant and anti-inflammatory properties. NAC has been shown to attenuate inflammation in various disease models such as ischemia-reperfusion injury in brain (Sekhon et al, 2003;Khan et al, 2004), lethal endotoxemia (Victor et al, 2003), animal model of multiple sclerosis (Lehmann et al, 1994;Stanislaus et al, 2005), and hypoxic-ischemic brain injury in neonatal brains (Jatana et al, 2006;Wang et al, 2007). In addition, we and others have reported the attenuation of brain white matter injury by NAC in the systemic maternal infection model of PVL (Cai et al, 2000;).…”

S-Nitrosoglutathione Reduces Inflammation and Protects Brain against Focal Cerebral Ischemia in a Rat Model of Experimental Stroke

“…Furthermore, the treatment with GSNO in vitro inhibited the cytokine and/or LPS-induced iNOS expression and cytokine and/or LPS-mediated NF-kB luciferase activity both in rat primary astrocytes and BV2 cells (Figures 7 and 8), indicating that GSNO is an antiinflammatory agent. Inflammatory components in stroke may be amenable to treatment by antiinflammatory agents (Barone and Feuerstein, 1999) including Nacetylcysteine (Khan et al, 2004;Sekhon et al, 2003). Cerebral ischemia promotes activation of glial cells (resident microglia and astrocytes) and infiltration of blood-borne cells including monocytes (del Zoppo et al, 2000;Garcia et al, 1994;Stoll et al, 1998), leading to inflammation.…”

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

“…Their results showed that NAC protected against free oxygen radical injury, apoptosis, and inflammation. 24 However, Thomale et al found that after brain contusion, NAC was not effective at reducing the area of injury and did not influence post-traumatic brain edema formation. 25 Cakir et al investigated the effect of NAC on spinal cord ischemia-reperfusion injury in rabbits.…”