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9 - Imaging in experimental neurology
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- By Marc Fisher, Department of Neurology University of Massachusetts Medical School UMASS/Memorial Health Care 119 Belmont Street Worcester, MA 01605 USA, Eng H. Lo, Departments of Neurology and Radiology Harvard Medical School Boston, MA 02115 USA, Michael Lev, Department of Radiology Harvard Medical School Boston, MA 02115 USA
- Edited by Turgut Tatlisumak, Marc Fisher
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- Book:
- Handbook of Experimental Neurology
- Published online:
- 04 November 2009
- Print publication:
- 05 October 2006, pp 132-146
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Summary
Introduction
The availability of advanced imaging techniques has revolutionized the evaluation of many clinical neurological disorders. Similarly, the availability of advanced imaging techniques has enhanced the utility of animal models related to the study of these disorders. Currently, the most available and useful imaging techniques in animal models of neurological disorders are those related to magnetic resonance imaging (MRI) applications, computerized tomography (CT), and positron emission tomography (PET). This chapter will introduce the basic concepts related to these various imaging modalities and then discuss their application to neurological disorders with a focus on acute ischemic brain injury.
Magnetic resonance imaging
A wide variety of MRI techniques are currently available for use in animals and patients. The range of MRI modalities and their main uses are provided in Table 9.1. The initial MRI modalities employed were T1- and T2-weighted imaging that evaluated the density of water proton spins. Water protons in relatively unrestricted fluid spaces have higher T1 and T2 values, while these protons in more restricted environments such as brain edema, hemorrhages, or tumors have lower values. These two MRI modalities are associated with an increase in interstitial water content of the brain, as seen with the development of vasogenic edema. Conventional T1 and T2 MRI have been used widely in clinical imaging for two decades and have also been used extensively in animal models of brain ischemia, tumors, traumatic injury, and multiple sclerosis (MS).
16 - Tissue plasminogen activator and hemorrhagic brain injury
- from Part V - Hemorrhage, edema and secondary injury
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- By Minoru Asahi, Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA, Rick M. Dijkhuizen, Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA; NMR Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, Xiaoying Wang, Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA, Bruce R. Rosen, NMR Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, Eng H. Lo, Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA
- Edited by Pak H. Chan, Stanford University, California
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- Book:
- Cerebrovascular Disease
- Published online:
- 02 November 2009
- Print publication:
- 28 March 2002, pp 181-191
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Summary
Effects of tissue-type plasminogen activator in acute clinical stroke
A rational approach to cerebral ischemia involves reperfusion of occluded arteries. Recent clinical trials have shown that thrombolytic therapy with tissue-type plasminogen activator (tPA) may be effective for acute ischemic stroke. However, there is also an elevated risk of cerebral hemorrhage and further brain injury. In all three of the major clinical trials (National Institute of Neurological Disorders and Stroke, European Cooperative Acute Stroke Study I and II), the odds ratio for intracerebral hemorrhage after tPA therapy was increased by about three-fold compared with placebo. The precise mechanisms that underlie these negative effects of tPA remain unclear, but are clearly related to severity of the ischemic insult as well as to the timing of tPA-induced reperfusion. In this chapter, the literature on the neurotoxic effects of tPA will be briefly discussed, and data from our own laboratory will be provided with which we examine some of these mechanisms.
Effects of tPA in experimental cerebral ischemia
Although tPA-induced reperfusion of ischemic brain tissue is expected to salvage tissue, recent reports from the experimental literature have suggested that tPA may have neurotoxic effects as well. Wang and colleagues have shown that infusion of tPA increased infarct size in a mouse model of focal cerebral ischemia. Potentially negative effects of tPA may be based on its ability to activate plasminogen and induce damaging extracellular proteolytic pathways. Specifically, non-fibrin substrates for plasmin, such as laminin, may be degraded.