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. 2018 Jan 15;8:744. doi: 10.3389/fneur.2017.00744

Table 3.

Outcome measures and summary of findings in 20 animal studies (21 experiments).

Reference Outcome(s) measured Summary of findings in N-acetylcysteine treated animals compared to controls
Abdel-Baki et al. (37) Variants of place avoidance task (56)
  • 1

    NAC + minocycline: improvement of active place avoidance (F4,25 = 34.68; p = 0.01).
Chen et al. (38) NH-kB; IL-1β; TNF-α; IL-6; ICAM-1 micro-vessels; brain water; BBB; cell apoptosis
  • 1

    NF-kB, UL-1β, IL-6, TNF-α, ICAM-1: upregulated following TBI and suppressed with NAC

  • 2

    NAC: ↓ Brain edema, barrier permeability, and apoptosis
Du et al. (39) 4-HNE; c-fos; amyloid beta (A4); APP; GFAP; NF-68; caspase 3
  • 1

    Blast exposure: upregulated 4-HNE, c-fos, GFAP, APP, and HNF 68

  • 2

    NAC: reduced the levels of all biomarkers in specific brain areas
Eakin et al. (40) MWM: hidden platform, probe trial, visible platform
  • 1

    Treatment group: Improved performance in MWM tasks, probe trial, and visible platform tasks (p < 0.05)
Eakin et al. (40) Novel object recognition; Y maze paradigm
  • 1

    Treatment group: significantly improved performance for both tasks (p < 0.05)
Ellis et al. (41) Mean arterial pressure
  • 1

    Cats receiving NAC demonstrated vasoconstriction (one of mechanism involved in oxidative stress)
Ewert et al., (42) ABR; DPOE level shifts; hair cell loss on cochlear histology
  • 1

    ABR threshold was 10 dB less at 24 h. Difference in thresholds was around 20 dB at 7 and 21 days between the treated and control group

  • 2

    DPOE levels shift recovered around 7d in treated group

  • 3

    Hair cell loss was significantly less in treated group
Gunther et al. (43) Fluro-Jade B; TUNEL; MnSOD; Ox-42; iNOS; 3-NT; NFkB; Caspase 3; Cytochrome C; bcl-2; Cy3; Alexa 488; Biotinyl
  • 1

    Significant lower levels of necrotic cell death and apoptosis

  • 2

    Levels of antioxidant enzyme MnSOD were significantly higher
Haber et al. (44) Four variants of place avoidance tasks (56). Brain sections of injured area
  • 1

    NAC + minocycline: performed better on conflict active place avoidance task and limited memory deficits

  • 2

    NAC + minocycline: associated with decreased CD68 expression and increased microglial activation.
Hicdonmez et al. (45) MDA; SOD activity; GPx activity; catalase activityNumber of neurons (/mm2); caspase 3 activity
  • 1

    Treatment group: significant increased activity of SOD and GPx at 12 h

  • 2

    Treatment group: significant GPx activity at 2 h

  • 3

    Morphology of neurons was well protected in the NAC group
Kawoos et al. (46) Intracranial pressure monitoring
  • 1

    Single NACA dose reduced ICP after single BOP induced injury

  • 2

    Single NACA dose was not effective in reducing ICP after multiple BOP

  • 3

    Two NACA doses were effective in reducing ICP after multiple BOP

  • 4

    A pre-injury NACA dose was most effective in reducing ICP after multiple BOP
Naziroglu et al. (47) Intracellular Ca2+; apoptosis; caspase activity, and ROS in hippocampal cells
  • 1

    NAC group: ↓ Intracellular free Ca2+, apoptosis, caspase 3 and 9 activity, and ROS levels

  • 2

    Se group: some effect, but NAC group had a much greater effect
Pandya et al. (48) Exp 1—tissue sparing; Exp 2—oxidative stress; Exp 3—mitochondrial bioenergetics and glutathione content; Exp 1–3 cognitive behavioral assessment
  • 1

    NACA: better than NAC for tissue sparing and cognitive behavior.

  • 2

    NACA: ↓ oxidative stress, improved mitochondrial bioenergetics, and maintenance of GSH
Senol et al. (20) Lipid peroxidation; GSH; GSH peroxidase; protein assay; brain cortex β-Carotene, Vitamins A, C, and E
  • 1

    NAC group: significantly higher levels of GSH, Vitamin A, Vitamin E, and total oxidant status
Silva et al., (49) Drug induced seizures; Na + K + ATPase activity; TBAR; protein carbonyl
  • 1

    NAC group: more protection from drug induced seizures and Na + , K + ATPase inhibition
Thomale et al. (50) Brain edema, ABG; ICP; contusion volume No differences were observed
Thomale et al. (51) MAP; ABG; CBF; ICP; water content; contusion volume No differences were observed
Xiong et al. (52) Mitochondrial activity; Ca + 2 content and transport; GSH
  • 1

    NAC: significant impact on mitochondrial bioenergetics and Ca uptake

  • 2

    NAC: restored GSH levels during the 14-day observation period
Xiong et al. (53) Apoptosis-related proteins; shortened bcl-2 and Bax; cytochrome c
  • 1

    NAC: diminished levels of shortened bcl-2 and Bax
Yi and Hazell (54) HO-1 activity in specific brain regions; volume of injury
  • 1

    NAC: lower levels of HO-1 in cerebral cortex, thalamus, and hippocampus

  • 2

    NAC: associated with significantly decreased volume of injury
Yi et al. (55) Complexin I and II; neuronal cell loss
  • 1

    NAC: reversed increased in Complexin levels in the injured cortex

  • 2

    NAC: significantly less neuronal cell loss

HNE, 4-hydroxy-2-nonenal; SOD, superoxide dismutase; ABG, arterial blood gas; ABR, auditory brain stem; BB, blood–brain barrier; BOP, blast overpressure; CBF, cerebral blood flow; c-fos, genetic biomarker; COWA, controlled oral word association test; DPOE, distortion product optoacoustic emissions; GPx, glutathione peroxidase; HO-1, hemeoxygenase -1; ICP, intracranial pressure; ICAM, intercellular adhesion Molecule-1; IL-1β, interleukin 1-beta; IL-6, interleukin 6; MPO, myeloperoxidase; MDA, melandialdehyde; NAC, N-acetylcysteine; NACA, N-acetylcysteine amide; NH-kB, nuclear factor kappa B; ROS, reactive oxygen species; Se, selenium; SOD, superoxide dismutase; TBAR, thiobarbituric acid reactive substances; TBI, traumatic brain injury; TNF-α, tumor necrosis factor alpha.