Source Paper
Guohua Wang, Yejie Shi, Xiaoyan Jiang, Rehana K. Leak, Xiaoming Hu et al.
Proceedings of the National Academy of Sciences • 2015
Significance Moderate or severe traumatic brain injury (TBI) damages white matter, thereby contributing to long-term neurological deficits. Currently, there are no satisfactory therapies to mitigate this white matter injury (WMI). Here we show that inhibition of histone deacetylases (HDACs) exerts robust structural and functional protection of white matter in a murine model of TBI/WMI by polarizing microglia/macrophages toward the beneficial M2 phenotype. HDAC inhibition shifted microglia/macrophage phenotype by up-regulating glycogen synthase kinase 3 beta (GSK3β), which inactivated phosphatase and tensin homologue (PTEN) through phosphorylation, thereby promoting PI3K/Akt signaling. The GSK3β-dependent M2 phenotype exerted potent anti-inflammatory effects that protected myelin-forming oligodendrocytes and diminished WMI. These results reveal a previously unexplored role for GSK3β/PTEN/PI3K signaling in the regulation of microglia/macrophages and demonstrate the promise of HDAC inhibition in the treatment of TBI/WMI.
Objective: To evaluate structural and functional protection of white matter in a murine model of traumatic brain injury using HDAC inhibition and assess microglia/macrophage polarization
This is a Traumatic Brain Injury Model protocol using mouse as the model organism. The procedure involves 10 procedural steps, 1 equipment items, 1 materials. Extracted from a 2015 paper published in Proceedings of the National Academy of Sciences.
Model and subjects
mouse • Not specified in provided text • unknown • Not specified in provided text • Not specified in provided text
Study window
~5 week study window
Core workflow
Traumatic Brain Injury Induction • HDAC Inhibitor Treatment • Assessment of Neurofilament Phosphorylation
Primary readouts
Key equipment and reagents
Verified items
0
Direct vendor links
0
Use this page as an execution guide, then fall back to the source paper whenever you need exact exclusions, dosing details, or assay-specific caveats.
Confirm first
Use the page like this
Start here. The step list is optimized for running the experiment, with direct vendor links available inline when you need to source a cited item.
Induce moderate or severe traumatic brain injury in murine subjects to create white matter injury model
Note: Model designed to damage white matter and contribute to long-term neurological deficits
“Moderate or severe traumatic brain injury (TBI) damages white matter, thereby contributing to long-term neurological deficits”
Administer Scriptaid to inhibit histone deacetylases and promote white matter protection
Note: Treatment shifts microglia/macrophage polarization toward M2 phenotype
“Scriptaid protects white matter up to 35 d after TBI, as shown by reductions in abnormally dephosphorylated neurofilament protein”
Measure abnormally dephosphorylated neurofilament protein levels as indicator of white matter protection
Note: Reductions in abnormal dephosphorylation indicate protective effects
“reductions in abnormally dephosphorylated neurofilament protein, increases in myelin basic protein”
Measure myelin basic protein levels to assess myelin preservation
Note: Increases in myelin basic protein indicate white matter protection
“increases in myelin basic protein, anatomic preservation of myelinated axons, and improved nerve conduction”
Evaluate anatomic preservation of myelinated axons through histological or imaging analysis
Note: Direct assessment of structural white matter integrity
“anatomic preservation of myelinated axons, and improved nerve conduction”
Measure nerve conduction velocity or function as functional indicator of white matter integrity
Note: Improved nerve conduction indicates functional protection
“improved nerve conduction”
Assess microglia/macrophage polarization toward M2 phenotype following Scriptaid treatment
Note: M2 phenotype associated with anti-inflammatory effects and white matter protection
“Scriptaid shifted microglia/macrophage polarization toward the protective M2 phenotype and mitigated inflammation”
Conduct in vitro studies using primary cocultures of microglia and oligodendrocytes to assess mechanism
Note: Scriptaid increases GSK3β expression in microglia, which phosphorylates and inactivates PTEN
“In primary cocultures of microglia and oligodendrocytes, Scriptaid increased expression of microglial glycogen synthase kinase 3 beta (GSK3β)”
Measure signaling pathway activation including GSK3β upregulation, PTEN phosphorylation, and PI3K/Akt enhancement
Note: GSK3β phosphorylates and inactivates PTEN, enhancing PI3K/Akt signaling
“GSK3β, which phosphorylated and inactivated phosphatase and tensin homologue (PTEN), thereby enhancing phosphatidylinositide 3-kinases (PI3K)/Akt signaling”
Evaluate preservation of oligodendrocytes in response to M2-polarized microglia
Note: Increased preservation of neighboring oligodendrocytes associated with microglial M2 phenotype
“increased preservation of neighboring oligodendrocytes. These findings are consistent with recent findings that microglial phenotypic switching modulates white matter repair”
This section explains what the experiment is doing, which readouts matter, what the data artifacts usually look like, and how the analysis should flow from raw capture to reported result.
To evaluate structural and functional protection of white matter in a murine model of traumatic brain injury using HDAC inhibition and assess microglia/macrophage polarization
Objective
To evaluate structural and functional protection of white matter in a murine model of traumatic brain injury using HDAC inhibition and assess microglia/macrophage polarization
Subjects
From papermouse • Not specified in provided text • unknown • Not specified in provided text • Not specified in provided text
Cohort notes
From paperMurine model used for TBI/WMI studies
Traumatic Brain Injury Induction (Not specified in provided text)
HDAC Inhibitor Treatment (Assessment conducted up to 35 days post-TBI)
Assessment of Neurofilament Phosphorylation (Not specified in provided text)
Assessment of Myelin Basic Protein (Not specified in provided text)
Reductions in abnormally dephosphorylated neurofilament protein
From paperNot specified in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Increases in myelin basic protein levels
From paperNot specified in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Anatomic preservation of myelinated axons
From paperNot specified in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Improved nerve conduction velocity/function
From paperNot specified in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Reductions in abnormally dephosphorylated neurofilament protein
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Increases in myelin basic protein levels
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Anatomic preservation of myelinated axons
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Improved nerve conduction velocity/function
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
Preprocessing / cleaning
Not specified in provided text
Scoring or quantification
Quantify the primary readouts for this experiment: Reductions in abnormally dephosphorylated neurofilament protein; Increases in myelin basic protein levels; Anatomic preservation of myelinated axons; Improved nerve conduction velocity/function.
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Reductions in abnormally dephosphorylated neurofilament protein, Increases in myelin basic protein levels, Anatomic preservation of myelinated axons, Improved nerve conduction velocity/function.
Source links and direct wording from the methods section for validation and deeper review.
Citation
Guohua Wang et al. (2015). HDAC inhibition prevents white matter injury by modulating microglia/macrophage polarization through the GSK3β/PTEN/Akt axis. Proceedings of the National Academy of Sciences
“”
“”
“”
“”
Direct vendor pages are linked from the protocol above. This section stays focused on the full comparison view and the prep checklist.
Gather these items before starting the experiment. Check off items as you prepare.
Not specified in provided text • Not specified in provided text • Not specified in provided text • Not specified in provided text
Not specified in provided text • Not specified in provided text • Not specified in provided text • Not specified in provided text
Not specified in provided text • Not specified in provided text
Use this section as the page quality checkpoint. It keeps section navigation, evidence access, readiness, and verification meaning in one place.
Current status surfaces were computed from experiment data updated Mar 14, 2026.
Source access
Jump back into the original paper or the methods evidence section when you need exact wording, exclusions, or method-specific caveats.
This protocol has structured steps plus evidence quotes, and is ready for canonical sync.
Steps
10
Evidence Quotes
12
Protocol Items
2
Linked Products
0
Canonical Sync
Pending
What this means
The completeness score reflects how much structured protocol data is present: steps, methods evidence, listed materials, linked products, and paper provenance.
Computed from the current experiment record updated Mar 14, 2026.
Canonical Sync shows whether a ConductGraph-backed protocol is available for this experiment route right now. It is a sync-status signal, not a claim that every downstream vendor link or step detail is perfect.
Steps
10
Evidence
12
Specific Products
0/0
Canonical Sync
Pending
What this score means
The verification score reflects evidence coverage, subject detail, paper provenance, step depth, and whether linked products resolve to specific item pages instead of generic searches.
Computed from the current experiment record updated Mar 14, 2026.
A page can have structured steps and still need review when evidence is thin, product links are generic, or canonical protocol coverage is still pending.
What still needs work