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Updated: Jul 19, 2025
Detecting Behavioral Deficits in Rats After Traumatic Brain Injury
Published on: January 30, 2018
HDAC inhibitor attenuates rat traumatic brain injury induced neurological impairments
Yiming Lu1, Yiming Chen1, Siyi Xu1
1Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Abstract:
Oxidative stress plays an important role in the secondary neuronal damage after traumatic brain injury (TBI). Inhibition of histone deacetylases (HDACs) has been shown to reduce reactive oxygen species (ROS) production and NADPH oxidases (Nox) transcription. Vorinostat is an HDAC inhibitor. This study investigated the influence of vorinostat on neurological impairments in a rat model of TBI induced by lateral fluid percussion injury (LFPI). Different concentrations of vorinostat (5, 25, and 50 mg/kg) were administered via intraperitoneal injection. Neurological deficits were evaluated by modified neurological severity scoring (mNSS). Evans blue extravasation was performed to assess blood-brain barrier (BBB) permeability. Morris water maze assay was performed to evaluate cognitive impairments. Protein levels were evaluated through ELISA and Western blot. Vorinostat was found to attenuate TBI induced brain edema and BBB permeability in rats. Vorinostat also alleviated TBI-induced neurological impairments and anxiety-like behavior in rats. Vorinostat attenuated TBI induced apoptosis and oxidative stresses in ipsilateral injury cortical tissue. Vorinostat inhibited HDAC1, HDAC3, and Nox4 while activated AMPK signaling in ipsilateral injury cortical tissue. In conclusion, administration of vorinostat alleviates the secondary damage of TBI in rat model. The oxidative stress in the ipsilateral injury cortical tissues is decreased by the inhibition of Nox4 expression and the activation of AMPK.
Insights
Vorinostat, an inhibitor of histone deacetylases (HDACs), reduces secondary brain damage after traumatic brain injury (TBI). This study shows vorinostat treatment improves neurological function and decreases oxidative stress in a rat TBI model.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Oxidative stress contributes to secondary neuronal damage following traumatic brain injury (TBI).
- Histone deacetylase (HDAC) inhibition can reduce reactive oxygen species (ROS) and NADPH oxidase (Nox) expression.
- Vorinostat is an FDA-approved HDAC inhibitor with potential neuroprotective properties.
Purpose of the Study:
- To investigate the therapeutic effects of vorinostat on neurological impairments in a rat model of TBI.
- To evaluate vorinostat's impact on oxidative stress, blood-brain barrier (BBB) permeability, and cognitive function post-TBI.
Main Methods:
- Traumatic brain injury was induced using lateral fluid percussion injury (LFPI) in rats.
- Vorinostat was administered intraperitoneally at varying doses (5, 25, 50 mg/kg).
- Neurological deficits, BBB permeability, cognitive function, apoptosis, oxidative stress, and protein levels (HDAC1, HDAC3, Nox4, AMPK) were assessed.
Main Results:
- Vorinostat administration attenuated TBI-induced brain edema and BBB permeability.
- Treatment with vorinostat alleviated neurological deficits, anxiety-like behavior, and apoptosis.
- Vorinostat inhibited HDAC1, HDAC3, and Nox4, while activating AMPK signaling in injured cortical tissue, reducing oxidative stress.
Conclusions:
- Vorinostat effectively alleviates secondary damage following TBI in a rat model.
- The neuroprotective effects are associated with the inhibition of Nox4 expression and activation of AMPK signaling, leading to reduced oxidative stress.
