pone.0221163.g001.tif (3.55 MB)

Schematic of experimental workflow and pilot studies.

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posted on 23.08.2019 by Stacy L. Sell, Deborah R. Boone, Harris A. Weisz, Cesar Cardenas, Hannah E. Willey, Ian J. Bolding, Maria-Adelaide Micci, Michael T. Falduto, Karen E. O. Torres, Douglas S. DeWitt, Donald S. Prough, Helen L. Hellmich

(A) The original hypothesis that diverse drugs with neuroprotective properties share common molecular mechanisms was validated by analysis of genome-wide microRNA expression profiles induced by three different drugs in rat brains after TBI. Unexpectedly, we found these microRNA profiles to be similar to those induced by antidepressant drugs. (B) Stereological assessment of neuronal injury after JM6 treatment reveals neuroprotective effect of JM6. JM6 treated rats had reduced numbers of FJC+ neurons in the CA1 (p = 0.19) and CA3 (p = 0.07) sub-regions of the hippocampus. The overall average (CA1 and CA3 taken together) was significantly different *p = .038 vs untreated. (C) Immunohistochemistry using CD11b (OX-42) shows JM6 reduced microglial activation after TBI. Increased microglial activation after TBI (left) is ameliorated by treatment with JM6 (right) in the rat hippocampus (upper) and cortex (lower). Note, in sham-injured brains (not shown), staining was undetectable.