Mature and Myelinating Oligodendrocytes Are Specifically Vulnerable to Mild Fluid Percussion Injury in Mice

• Published in: Neurotrauma reports 2023-06, Vol.4 (1), p.433-446
• Main Authors: Adams, Alexandra A, Wood, Teresa L, Kim, Haesun A
• Format: Article
• Language: English
• Subjects: BCAS1; CC1; corpus callosum; FluoroMyelin?; GST-?; mild TBI; Original
• ISSN: 2689-288X; 2689-288X
• DOI: 10.1089/neur.2023.0037

Myelin loss and oligodendrocyte death are well documented in patients with traumatic brain injury (TBI), as well as in experimental animal models after moderate-to-severe TBI. In comparison, mild TBI (mTBI) does not necessarily result in myelin loss or oligodendrocyte death, but causes structural alterations in the myelin. To gain more insight into the impact of mTBI on oligodendrocyte lineage in the adult brain, we subjected mice to mild lateral fluid percussion injury (mFPI) and characterized the early impact (1 and 3 days post-injury) on oligodendrocytes in the corpus callosum using multiple oligodendrocyte lineage markers (platelet-derived growth factor receptor [PDGFR]-α, glutathione -transferase [GST]-π, CC1, breast carcinoma-amplified sequence 1 [BCAS1], myelin basic protein [MBP], myelin-associated glycoprotein [MAG], proteolipid protein [PLP], and FluoroMyelin™). Two regions of the corpus callosum in relation to the impact site were analyzed: areas near (focal) and anterior (distal) to the impact site. mFPI did not result in oligodendrocyte death in either the focal or distal corpus callosum, nor impact on oligodendrocyte precursors (PDGFR-α ) and GST-π oligodendrocyte numbers. In the focal but not distal corpus callosum, mFPI caused a decrease in CC1 as well as BCAS1 actively myelinating oligodendrocytes and reduced FluoroMyelin intensity without altering myelin protein expression (MBP, PLP, and MAG). Disruption in node-paranode organization and loss of Nav1.6 nodes were observed in both the focal and distal regions, even in areas without obvious axonal damage. Altogether, our study shows regional differences in mature and myelinating oligodendrocyte in response to mFPI. Further, mFPI elicits a widespread impact on node-paranode organization that affects regions both close to and remotely located from the site of injury.