FK506 Protects Neurons Following Peripheral Nerve Injury Via Immunosuppression |
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Authors: | Kapil Saxena Nisha Patro Ishan Patro |
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Institution: | (1) School of Studies in Neuroscience, Jiwaji University, Gwalior, Madhya Pradesh, 474011, India;(2) Institute of Applied Science and Computer Applications, ITM Universe, Gwalior, 474011, India;(3) School of Studies in Zoology, Jiwaji University, Gwalior, 474011, India |
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Abstract: | In this study, we have evaluated neuroprotective effect of an immunosuppressant immunophilin ligand, FK506, in the sciatic
nerve injury model in rats. FK506 was injected to the sciatic nerve transected 3-month-old female Wistar rats (2 mg/kg/day
starting 1 day prior to sciatic nerve injury up to 7 day post operation). Equal number of sciatic nerve transected animals
served as injured untreated controls. The contralateral side served as respective control. L4-L5 region of the spinal cord
was removed on day 1, 3, 7, 14, 21, and 28, post operation and then processed for cryo-sectioning and paraffin sectioning.
The cryocut sections were used for immunohistochemistry for localizing all microglia (using anti-Iba-1) and MHC-II expressing
microglia (with OX-6). The physical dissector method was applied on Nissl stained paraffin sections for absolute motor neuron
counting in the L4-L5 region of spinal cord. FK506 treated animals presented 88.7% neuronal survival while the injured alone
had 79.12%, which is significantly less than the treated animals. FK506 caused early proliferation of microglia at 1 and 3 days
post operation. FK506 also significantly restricted transformation of these cells in to phagocytes. Colocalization of activated
microglia by anti-Iba-1 and OX-6 antibodies, confirms that the MHC-II expressing cells in injured spinal cord are none other
than microglial cells and MHC-II expressing cells are significantly less in treated as compared to untreated injured animals.
We propose that immunosuppression is one of the main mechanisms by which FK506 protects the central neurons following peripheral
injury. |
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Keywords: | FK506 Microglia Sciatic nerve injury Immunosuppression Neuroprotection |
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