Experimental neurology
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Experimental neurology · Feb 2006
Comparative StudyAdministration of the immunophilin ligand FK506 differentially attenuates neurofilament compaction and impaired axonal transport in injured axons following diffuse traumatic brain injury.
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 treatment failed to reduce the number of axons demonstrating NFC in either the CSpT or ML. FK506's failure to attenuate NFC suggests that additional therapeutic agents may be necessary to blunt the full burden of TAI. Because FK506 targets IAT, calcineurin appears to be a major target for neuroprotection in damaged axons demonstrating IAT.