Abstract Details

Title Restoration of Barnes maze, Protein Kinase M? and MAP2 by Minocycline plus N-Acetylcysteine when first dosed 72 hours after experimental traumatic brain injury

Topic Neuro-rehabilitation

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 7-014

Objective

We investigated whether the drug combination of minocycline plus N-acetylcysteine dosed 72 hours after injury (MN72) altered the expression of MAP2 and PKMζ, two key proteins that mediate synaptic function and plasticity.

Background Traumatic Brain Injury (TBI) produces long-term deficits in cognition and memory. Most therapeutic options rapidly lose potency as time to first dose increases; this is one reason why there are currently no drugs to treat TBI. We previously showed that MN72 allows mice to learn Barnes maze, a task that requires one functioning hippocampus. Examination of long-term synaptic plasticity in both hippocampi showed plasticity was restored only in the hippocampus contralateral to the injury site.

Design/Methods We tested whether MN72 either maintained or restored expression by examining how MAP2 and PKMζ expression changed after injury in the ipsilateral and contralateral hippocampus of injured mice treated with saline or MN72.

Results Neither the saline nor MN72 groups recovered expression of MAP2 or PKMz in the ipsilateral hippocampus between 3 and 60 days post-injury (DPI). At 14DPI, the contralateral hippocampus of the MN72-treated mice increased MAP2 expression to sham-injured levels; in contrast, saline-treated mice only increased MAP2 expression at 60DPI. These data suggest acceleration of MAP2 recovery by MN72 in the contralateral hippocampus. The saline and MN72 groups had reduced PKMζ expression at 3 and 7 DPI in the contralateral hippocampus. PKMζ expression in the MN72 group increased at 14 and 60DPI. In contrast to MAP2, PKMζ expression in the contralateral hippocampus of the saline group never recovered by 60DPI.

Conclusions

These data suggest that MN72 accelerated MAP2 recovery yet restored PKMζ protein levels in the contralateral hippocampus. The de novo recovery of PKMζ expression suggests that MN72 repaired the contralateral hippocampus and reversed the deficits in synaptic plasticity, cognition and memory produced by head injury.

Authors/Disclosures
Syed Rahman PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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