Efficacy of N-Acetyl Cysteine in Traumatic Brain Injury

Eakin, Katharine; Baratz-Goldstein, Renana; Pick, Chiam G.; Zindel, Ofra; Balaban, Carey D.; Hoffer, Michael E.; Lockwood, Megan; Miller, Jonathan P.; Hoffer, Barry J.

doi:10.1371/journal.pone.0090617

Cited by 89 publications

(80 citation statements)

References 40 publications

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“…Previous studies 55,56 have supported antioxidants as neuroprotective agents in rats and humans, revealing that administration of N -acetylcysteine reduces brain damage and improves recovery after TBI. N -acetylcysteine is the cellular precursor to glutathione.…”

Section: Therapeutic Modulation Of Tbi Pathogenesismentioning

confidence: 91%

Inflammation and Neuroprotection in Traumatic Brain Injury

2015

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IMPORTANCE Traumatic brain injury (TBI) is a significant public health concern that affects individuals in all demographics. With increasing interest in the medical and public communities, understanding the inflammatory mechanisms that drive the pathologic and consequent cognitive outcomes can inform future research and clinical decisions for patients with TBI.OBJECTIVES To review known inflammatory mechanisms in TBI and to highlight clinical trials and neuroprotective therapeutic manipulations of pathologic and inflammatory mechanisms of TBI.

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Section: Therapeutic Modulation Of Tbi Pathogenesismentioning

confidence: 91%

Inflammation and Neuroprotection in Traumatic Brain Injury

2015

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“…N-acetylcysteine administered 30 min post-TBI in rats resulted in improved MWM performance to near sham-injured levels [273]. When administered 60 min post-weight drop injury in mice, functional deicits in novel object recognition and Y-maze were signiicantly improved [273]. In combination with minocycline, N-acetylcysteine has been shown to act synergistically to reduce TBI-induced demyelination, augment M2 microglia activation in white mater and modulate TBI-induced neuroinlammation, increasing microglial activation yet decreasing the number of injury-induced phagocytic CD68+ macrophages in the corpus callosum.…”

Section: N-acetylcysteinementioning

confidence: 92%

Section: N-acetylcysteinementioning

confidence: 99%

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

Dugue¹,

Nath²,

Dugue³

et al. 2017

Mechanisms of Neuroinflammation

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This chapter will introduce the reader to the pathophysiology of two devastating neurologic events, traumatic brain injury (TBI) and acute ischemic stroke (AIS). Here we focus on the role of key pro-inlammatory and anti-inlammatory cytokines. Several experimental interventions have been found to modulate cytokine production and brain injury after AIS or TBI. Here minocycline, biological response modiiers, hormonal therapies, omega-3 faty acids, N-acetylcysteine, and cannabinoids will be discussed. In addition, the role of cytokine-induced inlammasomes in both TBI and AIS will be addressed and followed by discussion of pro-inlammatory cytokines (e.g., TNF-α, IL-1β, IL-18, and IFN-γ). Finally, the main anti-inlammatory cytokines, IL-33, IL-10, IL-6, and IL-4, will be discussed in the context of both TBI and AIS. It should be noted that the role of these cytokines is diverse and the dichotomization of classically pro-versus anti-inlammatory cytokines is being re-examined, as many of these cytokines have been found to play dual roles in TBI and AIS brain injury.Keywords: traumatic brain injury, ischemic stroke, cytokines, interleukins, inlammasome Pathophysiology of traumatic brain injuryTraumatic brain injury (TBI) is a major cause of death and disability worldwide [1,2]. It is one of the most commonly diagnosed neurological disorders in the United States, impacting people of a variety of ages and segments of society [3]. In Europe, the economic cost of © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.TBI is over 33 billion euros per year [4]. Continued surveillance and research is being done to reduce primary and secondary TBI [as well as acute ischemic stroke(AIS)]-induced brain injury [1].The pathophysiology of TBI begins with the initial brain trauma (i.e., the primary injury). This primary injury results from mechanical damage that disrupts the blood-brain barrier (BBB), alters the vasculature and damages brain tissue. The resulting injured glia and neurons release their intracellular contents (i.e., damage-associated molecular paterns; (DAMPs)) into the extracellular space and activate neighboring glia and neurons. Activated glia and neurons then produce molecular signals that can both exacerbate and mend the acute injury and contribute to long-term recovery [5][6][7][8][9]. These downstream molecular and cellular processes (i.e., the secondary injury in TBI) are the focus of many pre-clinical and clinical therapeutic studies. Secondary injury in TBI involves a host of molecular and cellular responses to the The pathophysiology of AIS and TBI share common mechanisms. The initial insult in AIS, an occlusion of blood low resulting in a core infarct zone surrounded by a poorly perfused penumbra, versus the initial primary physical impact in TBI both result in pe...

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“…103 NAC effects on TBI are controversial, with some studies showing extended behavioral recovery after injury. 104,105 Enzogenol is well tolerated and may reduce self-perceived cognitive failures in patients 3 to 12 mo postmTBI 106 and can improve clinical outcomes after TBI. 105 Cerebrolysin is a parenterally administered neuropeptide preparation that can penetrate the BBB and can act in a manner similar to endogenous neurotrophic factors.…”

Section: Secondary Insults Related To the Dopamine Systemmentioning

confidence: 99%

“…This may contribute to the pathophysiology of cerebral damage following brain injury that is responsive to antioxidant treatments such as N-acetyl cysteine. 104,113 Even mTBI induces changes in immunoreactivity for inducible transcription factors (e.g., c-Fos, c-Jun, JunB and Krox-24, etc.) in areas related to fear condition (e.g., amygdala), reward effects, and working memory (e.g., hippocampus, striatum, NAC, etc.…”

Section: Secondary Insults Related To the Dopamine Systemmentioning

confidence: 99%

Impact of traumatic brain injury on dopaminergic transmission

et al. 2017

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Brain trauma is often associated with severe morbidity and is a major public health concern. Even when injury is mild and no obvious anatomic disruption is seen, many individuals suffer disabling neuropsychological impairments such as memory loss, mood dysfunction, substance abuse, and adjustment disorder. These changes may be related to subtle disruption of neural circuits as well as functional changes at the neurotransmitter level. In particular, there is considerable evidence that dopamine (DA) physiology in the nigrostriatal and mesocorticolimbic pathways might be impaired after traumatic brain injury (TBI). Alterations in DA levels can lead to oxidative stress and cellular dysfunction, and DA plays an important role in central nervous system inflammation. Therapeutic targeting of DA pathways may offer benefits for both neuronal survival and functional outcome after TBI. The purpose of this review is to discuss the role of DA pathology in acute TBI and the potential impact of therapies that target these systems for the treatment of TBI.

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Efficacy of N-Acetyl Cysteine in Traumatic Brain Injury

Cited by 89 publications

References 40 publications

Inflammation and Neuroprotection in Traumatic Brain Injury

Inflammation and Neuroprotection in Traumatic Brain Injury

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

Impact of traumatic brain injury on dopaminergic transmission

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