Topographical and quantitative assessment of white matter injury following a focal ischaemic lesion in the rat brain

Yam, P.S. , Patterson, J., Graham, D.I., Takasago, T., Dewar, D. and McCulloch, J. (1998) Topographical and quantitative assessment of white matter injury following a focal ischaemic lesion in the rat brain. Brain Research Protocols, 2(4), pp. 315-322. (doi: 10.1016/S1385-299X(98)00005-1) (PMID:9630700)

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Abstract

Axonal injury following cerebral ischaemia has attracted less attention than damage in grey matter. However, it is becoming increasingly recognised that axons are highly vulnerable to focal ischaemia [D. Dewar, D.A. Dawson, Changes of cytoskeletal protein immunostaining in myelinated fibre tracts after focal cerebral ischaemia in the rat, Acta. Neuropathol., 93 (1997) 71–77] [2]; [L. Pantoni, J.H. Garcia, J.A. Gutierrez, Cerebral white matter is highly vulnerable to ischemia, Stroke, 27 (1996) 1641–1647] [10]; [P.S. Yam, T. Takasago, D. Dewar, D.I. Graham, J. McCulloch, Amyloid precursor protein accumulates in white matter at the margin of a focal ischaemic lesion, Brain Res., 760 (1997) 150–157] [15]. Since white matter does not contain neuronal cell bodies or synapses it is likely that the mechanisms of injury and strategies for its protection are different from those in grey matter. In order that the effect of therapeutic intervention on the protection of axons can be assessed, a method by which axonal injury can be mapped and quantified is required. For this purpose, we investigated immunocytochemical methods using amyloid precursor protein (APP) following permanent middle cerebral artery occlusion in the rat. APP is transported by fast anterograde axonal transport [E.H. Koo, S.S. Sisodia, D.R. Archer, L.J. Martin, A. Weidemann, K. Beyreuther, P. Fischer, C.L. Masters, D.L. Price, Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport, Proc. Natl. Acad. Sci. U.S.A. 87 (1990) 1561–1565] [7]and has been shown to accumulate following a variety of insults to axons, indicative of dysfunction of axonal transport [R.N. Kalaria, S.U. Bhatti, E.A. Palatinsky, D.H. Pennington, E.R. Shelton, H.W. Chan, G. Perry, W.D. Lust, Accumulation of the beta amyloid precursor protein at sites of ischemic injury in rat brain, Neuroreport, 4 (1993) 211–214] [4]; [T. Kawarabayashi, M. Shoji, Y. Harigaya, H. Yamaguchi, S. Hirai, Expression of APP in the early stage of brain damage, Brain Res., 563 (1991) 334–338] [5]; [N. Otsuka, M. Tomonaga, K. Ikeda, Rapid appearance of beta-amyloid precursor protein immunoreactivity in damaged axons and reactive glial cells in rat brain following needle stab injury, Brain Res., 568 (1991) 335–338] [9]; [K. Shigematsu, P.L. McGeer, Accumulation of amyloid precursor protein in neurons after intraventricular injection of colchicine, Am. J. Pathol., 140 (1992) 787–794] [12]. We have been able to map the topographical relationship between APP accumulation and region of infarction using immunocytochemistry and image analysis techniques. Additionally, using a semi-quantitative scoring system, we have demonstrated that there is a relationship between the amount of APP accumulation and the volume of infarction following middle cerebral artery occlusion. These methods will be useful in the future for the assessment of therapeutic interventions on the protection of axons following ischaemic injury.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dewar, Dr Deborah and Graham, Professor David Ian and Patterson, Dr James and Yam, Dr Philippa and McCulloch, Mr James
Authors: Yam, P.S., Patterson, J., Graham, D.I., Takasago, T., Dewar, D., and McCulloch, J.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Brain Research Protocols
Publisher:Elsevier
ISSN:1385-299X
Published Online:07 December 1998

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