Retrograde neuronal cell death in the facial nucleus after axotomy in the brainstem -alteration of MMPs expression, cell migration and axonal regrowth-

• Project/Area Number: 14571302
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: KANAZAWA UNIVERSITY
• Principal Investigator: HASEGAWA Mitsuhiro Kanazawa University, Graduate School of Medical Science, Associate Professor, 医学系研究科, 助教授 (70218460)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: MMPs / facial nerve injury / retrograde degeneration / Schwann cell / brainstem / facial nucleus / peripheral nerve transplantation

Research Abstract

The aim of this study is to establish a model to investigate the unknown mechanism of retrograde neuronal cell death in the facial nucleus after axotomy at various lesions.In addition, the neuroprotective effects of autografted peripheral nerve tissues, and alteration of MMPs expression are investigated.The models include brainstem injury model ; the genu of the facial nerve tract in the brainstem is stereotactically transected, control injury model ; the brainstem near the facial nucleus is injured without transection of the facial nerve tract, distal injury model ; the facial nerve is cut at the stylomastoid foramen, proximal injury model ; the facial nerve is avuked at the stylomastoid foramen resulting in more proximal transection than the distal injury model, and transplanted model ; PNS autograft is transplanted to the injury site of the brainstem injury model.On day 7, compared with the contralateral side, the survival ratio of motoneurons of the facial nuclei is 105.8±3.8% in t he control injury group, 102.4±5.2% in the distal injury group; 94.6±7.4% in the proximal injury group, 30.9±8.3% in the brainstem injury group, 43.7±6.2% in the transplanted group. On day 28, the survival ratio is 96.4±5.0% in the control injury group, 90.2±3.0% in the distal injury group, 49.7±6.3% in the proximal injury group, 2.3±1.2% in the brainstem injury group, 20.4±5.1% in the transplanted group. In gelatin zymography and immunobistochemistry MIMiP-9 was expressed in injury site on day 1 with a peak on day 3.MMP-2 was expressed on day 1 and lasted for 7 days. In situ zymography showed gelatinase activity at the lesion site.These results suggest that the brainstem lesion model used in this study causes a massive neuronal cell death and this was partialiy rescued by the PNS autograft transplantation. MIMPs may play a role to regulate migration of inflammatory cells at the early stage of the injury.The transplantation of the PNS autograft has significant neuroprotective effects for retrograde degeneration.