Neuroprotective Effects of N-acetylcysteine on Experimental Closed Head Trauma in Rats

Abstract

N-acetylcysteine (NAC) is a precursor of glutathione, a potent antioxidant, and a free radical scavenger. The beneficial effect of NAC on nervous system ischemia and ischemia/reperfusion models has been well documented. However, the effect of NAC on nervous system trauma remains less understood. Therefore, we aimed to investigate the therapeutic efficacy of NAC with an experimental closed head trauma model in rats. Thirty-six adult male Sprague-Dawley rats were randomly divided into three groups of 12 rats each: Group I (control), Group II (trauma-alone), and Group III (trauma+NAC treatment). In Groups II and III, a cranial impact was delivered to the skull from a height of 7 cm at a point just in front of the coronal suture and over the right hemisphere. Rats were sacrificed at 2 h (Subgroups I-A, II-A, and III-A) and 12 h (Subgroups I-B, II-B, and III-B) after the onset of injury. Brain tissues were removed for biochemical and histopathological investigation. The closed head trauma significantly increased tissue malondialdehyde (MDA) levels (P < 0.05), and significantly decreased tissue superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities (P < 0.05), but not tissue catalase (CAT) activity, when compared with controls. The administration of a single dose of NAC (150 mg/kg) 15 min after the trauma has shown protective effect via decreasing significantly the elevated MDA levels (P < 0.05) and also significantly (P < 0.05) increasing the reduced antioxidant enzyme (SOD and GPx) activities, except CAT activity. In the trauma-alone group, the neurons became extensively dark and degenerated into picnotic nuclei. The morphology of neurons in the NAC treatment group was well protected. The number of neurons in the trauma-alone group was significantly less than that of both the control and trauma+NAC treatment groups. In conclusion, the NAC treatment might be beneficial in preventing trauma-induced oxidative brain tissue damage, thus showing potential for clinical implications.

Immunohistochemical investigation of caspase-3 in neuronal apoptosis after experimental closed head trauma

“…In this study, closed head trauma caused severe degenerative changes, shrunken cytoplasma and extensively dark picnotic nuclei in neurons of the frontal cortex tissues. This observation is in agreement with previous studies, which suggest that closed head trauma caused severe degenerative changes in neurons of frontal cortex and NAC treatment prevented this neuronal damage (Hicdonmez et al, 2006).…”

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

“…They reported favorable effects of NAC treatment on the oxidative brain tissue injury induced by the trauma. 27 However, in a study on rats with moderate left focal cortical contusion trauma, Thomale et al found that 163 mg/kg of NAC applied intraperitoneally 2-4 h after the brain injury was ineffective against post-traumatic perfusion, brain edema or contusion volume. 28 Cuzzocrea et al investigated the effect of NAC on brain ischemic injury in gerbils.…”

Roles of Pro- and Anti-inflammatory Cytokines in Traumatic Brain Injury and Acute Ischemic Stroke

“…N-acetylcysteine has been shown to have anti-inlammatory and antioxidant actions, increasing glutathione synthesis to scavenge ROS, decreasing IL-1β and TNF-α levels in brain injury, decreasing caspase-3 levels, and shifting microglia towards M2 anti-inlammatory phenotypes [268][269][270][271].…”