کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3057632 1186605 2006 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Administration of the immunophilin ligand FK506 differentially attenuates neurofilament compaction and impaired axonal transport in injured axons following diffuse traumatic brain injury
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Administration of the immunophilin ligand FK506 differentially attenuates neurofilament compaction and impaired axonal transport in injured axons following diffuse traumatic brain injury
چکیده انگلیسی

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 ≤ 0.05) and in the ML from 78.62 ± 16.87 to 41.00 ± 5.80 (P ≤ 0.05). 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 197, Issue 2, February 2006, Pages 353–362
نویسندگان
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