Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Topographical and quantitative assessment of white matter injury following a focal ischaemic lesion in the rat brain. 963 Jul

All three major isoforms of nitric oxide synthase (NOS) are expressed in the brain. Because of complex and overlapping expression patterns (Marletta, 1994; Nathan and Xie, 1994), the particular NOS isoform involved in many processes is not clear. In fact, NO generated by separate isoforms may have different roles and potentially opposing effects (Iadecola et al., 1994). We have taken a genetic approach, to disrupt or knockout the genes for NOS isoforms to circumvent some of the limitations of pharmacologic agents. This approach allows the study of each individual NOS isoform in physiologic processes in the context of intact animals. It gives insights into possible developmental roles for NO and parallel processes that may compensate for the absence of each NOS isoform. We have made nNOS and eNOS knockout mice, as well as double knockout mice that lack both nNOS and eNOS isoforms (Huang et al., 1993; Huang et al., 1995; Son et al., 1996). In this chapter, we review some of the physiologic roles for NO that have been elucidated making use of these mice, including regulation of cerebral blood flow, response to cerebral ischemia, regulation of neurotransmitter release in the brain, and development of synaptic plasticity. Other chapters will discuss results using NOS knockout animals in studies of long term potentiation (see Hawkins, this volume), neuronal development (see Mize, this volume), and potential mechanisms for protection in nNOS knockout mice (Moskowitz, M.A.; Dawson, V.L, this volume).
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PMID:Genetic analysis of NOS isoforms using nNOS and eNOS knockout animals. 993 31