Why do all drugs work in animals but none in stroke patients? 2 Neuroprotective therapy

Why do all drugs work in animals but none in stroke patients? 2 Neuroprotective therapy From the Department of Neurology. University of Texas Medical School at Houston, TX. USA Introduction The implication of the title of this paper is that animal models are not relevant to human stroke. In this paper, I will review neuronal-protective therapy and how animal models have helped us unravel the biochemical abnormalities occurring as a result of cerebral ischaemia and upon which neuronal-protective therapies are based. However, we will also discuss the limits of animal models, which have to be understood in relationship to the complexities of the clinical problem of stroke. Most neuronal-protective therapies are based on the pivotal role of calcium in causing post-ischaemic neuronal injury. As a result of membrane depolarization and release of excitatory neurotransmitters, calcium enters neurons through both voltage-operated and receptor-operated channels. In concert with the release of sequestered intracellular calcium, various proteolytic enzymes, protein kinases, and phospholipases are activated. Numerous cellular perturbations ensue, including production of nitric oxide and generation of free radicals secondary to breakdown of membrane phospholipids. Whilst the molecular biology of these post-ischaemic events is still only partially understood, pharmacotherapy has been designed to block each of the steps along this cascade of events. Before we discuss each http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Internal Medicine Wiley

Why do all drugs work in animals but none in stroke patients? 2 Neuroprotective therapy

Journal of Internal Medicine, Volume 237 (1) – Jan 1, 1995

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Publisher
Wiley
Copyright
1995 Blackwell Publishing Ltd
ISSN
0954-6820
eISSN
1365-2796
D.O.I.
10.1111/j.1365-2796.1995.tb01145.x
Publisher site
See Article on Publisher Site

Abstract

From the Department of Neurology. University of Texas Medical School at Houston, TX. USA Introduction The implication of the title of this paper is that animal models are not relevant to human stroke. In this paper, I will review neuronal-protective therapy and how animal models have helped us unravel the biochemical abnormalities occurring as a result of cerebral ischaemia and upon which neuronal-protective therapies are based. However, we will also discuss the limits of animal models, which have to be understood in relationship to the complexities of the clinical problem of stroke. Most neuronal-protective therapies are based on the pivotal role of calcium in causing post-ischaemic neuronal injury. As a result of membrane depolarization and release of excitatory neurotransmitters, calcium enters neurons through both voltage-operated and receptor-operated channels. In concert with the release of sequestered intracellular calcium, various proteolytic enzymes, protein kinases, and phospholipases are activated. Numerous cellular perturbations ensue, including production of nitric oxide and generation of free radicals secondary to breakdown of membrane phospholipids. Whilst the molecular biology of these post-ischaemic events is still only partially understood, pharmacotherapy has been designed to block each of the steps along this cascade of events. Before we discuss each

Journal

Journal of Internal MedicineWiley

Published: Jan 1, 1995

References

  • Glutamate and the pathophysiology of hypoxic‐ischemic brain damage
    Rothman, Rothman; Olney, Olney
  • The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system
    Monaghan, Monaghan; Bridges, Bridges; Cotman, Cotman
  • CGS 19755. a competitive NMDA receptor antagonist, reduces calcium–calmodulin binding and improves outcome after global cerebral ischemia
    Grotta, Grotta; Picone, Picone; Ostrow, Ostrow; Strong, Strong; Earls, Earls; Yao, Yao

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