Yam, P. S. , Dunn, L. T., Graham, D. I., Dewar, D. and McCulloch, J. (2000) NMDA receptor blockade fails to alter axonal injury in focal cerebral ischemia. Journal of Cerebral Blood Flow and Metabolism, 20(5), pp. 772-779. (doi: 10.1097/00004647-200005000-00003) (PMID:10826527)
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Abstract
The ability of the NMDA receptor antagonist, MK-801, to protect myelinated axons after focal cerebral ischemia has been examined. Amyloid precursor protein (APP) immunocytochemistry was used to assess the anatomic extent of axonal injury, and conventional histopathology was used to assess the volume of ischemic damage to neuronal perikarya. The middle cerebral artery was permanently occluded in 16 cats. The cats were treated with either vehicle or MK-801 as a 0.5-mg/kg bolus at 15 minutes before middle cerebral artery occlusion, followed by an infusion of 0.14 mg/kg per hour. After 6 hours, the animals were killed and the brains processed for histology and immunocytochemistry. The volume of neuronal necrosis was determined from 16 preselected coronal levels of the brain. The circumscribed zones of APP accumulation in axons were mapped onto images at the same 16 coronal levels, and quantitative analysis was performed using a transparent counting grid, randomly placed over each image. The histologic appearance and anatomic location of axons with increased APP immunoreactivity was similar in animals treated with vehicle and MK-801. MK-801 failed to reduce the hemispheric APP score significantly. In vehicle-treated animals, there was a significant association between the volume of neuronal necrosis and the amount of APP immunoreactivity. MK-801 significantly reduced the slope of the association between the volume of neuronal necrosis and the amount of APP immunoreactivity compared with that observed in vehicle-treated animals. As a result, the ratio of hemispheric APP score and volume of neuronal necrosis was significantly increased with MK-801 treatment. The inability of NMDA receptor antagonists to protect axons may limit their functional efficacy in improving functional outcome after stroke.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Dunn, Mr Laurence and Dewar, Dr Deborah and Graham, Professor David Ian and Yam, Dr Philippa and McCulloch, Mr James |
| Authors: | Yam, P. S., Dunn, L. T., Graham, D. I., Dewar, D., and McCulloch, J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | Journal of Cerebral Blood Flow and Metabolism |
| Publisher: | SAGE Publications |
| ISSN: | 0271-678X |
| ISSN (Online): | 1559-7016 |
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