The neuronal cytoskeleton is at risk after mild and moderate brain injury

Recent studies have described alterations in cytoskeletal proteins such as microtubule-associated protein 2 (MAP-2) and neurofilament (NF) resulting f rom moderate and severe experimental brain injury; however, few have invest igated the consequences of mild injury, which is associated clinically and experimentally with cognitive dysfunction and neuronal damage, To contrast cytoskeletal changes within 7 days following mild injury with those followi ng moderate injury, we subjected anesthetized, adult rats to mild (1.1-1.3 atm) or moderate (2.3-2.5 atm) lateral fluid percussion brain injury or sha m injury, Rats were sacrificed at 6 h (n = 4 mild; n = 4 moderate; n = 2 sh am), 24 h (n = 4 mild; n = 4 moderate; n = 1 sham), or 7 days (n = 5 mild; n = 4 moderate; rt = 1 sham) following injury, and immunohistochemistry was performed for MAP-2 and NF, Both mild and moderate injury produced notable cytoskeletal changes in multiple brain regions; however, mild injury gener ally resulted in a lesser degree of MAP-2 and NF loss over a smaller spatia l extent, When compared to moderately injured animals, animals subjected to mild injury showed substantially delayed MAP-2 and NF alterations within t he cortex and hippocampal dentate gyrus and no evidence of MAP-2 loss in th e hippocampal CA3 region, While mild and moderate injury resulted for the m ost part in similar patterns of axonal injury, tissue tears in the fimbria and loss of NF immunoreactivity in regions containing injured axons were on ly observed following moderate injury. Elucidating the effects of modulatin g injury severity may yield insight into the mechanisms involved in traumat ic damage to the cytoskeleton and guide future treatment strategies.