Administration of the immunophilin ligand FK506 differentially attenuates neurofilament compaction and impaired axonal transport in injured axons following diffuse traumatic brain injury.

摘要

Traumatic axonal injury (TAI) following traumatic brain injury (TBI) remains a clinical problem for which no effective treatment exists. TAI was thought to involve intraaxonal changes that universally led to impaired axonal transport (IAT), disconnection and axonal bulb formation. However, recent, immunocytochemical studies employing antibodies to amyloid precursor protein (APP), a marker of IAT and antibodies to neurofilament compaction (NFC), RM014, demonstrated that NFC typically occurs independent of IAT, indicating the existence of different populations of damaged axons. FK506 administration has been shown to attenuate IAT. However, in light of the above, the ability of FK506 to attenuate axonal damage demonstrating NFC requires evaluation. The current study explored the potential of FK506 to attenuate both populations of damaged axons. Rats were administered FK506 (3 mg/kg) or vehicle 30 min preinjury. Three hours post-TBI, tissue was prepared for the visualization of TAI using antibodies targeting IAT (APP) or NFC (RMO14) or a combined labeling strategy. Confirming previous reports, FK506 treatment reduced the number of axons demonstrating IAT in the CSpT, from 411 +/- 54.70 to 91.00 +/- 33.87 (P