Saturday, October 03, 2015

Musing: The Science of Stroke - Mechanisms in Search
      of Treatments Dr. Michael A. Moskowitz

Dean Reinke
Deans’ Stroke Musing
Monday, March 7, 2011

When I first saw this referred to in ten steps forward in stroke research I knew I had to find it. I was unable to locate a free copy on the web so I contacted my local library and the librarian agreed to find me a copy from a partner library, but she ended up finding a free copy on the web; This is just the introduction, check out the URL if you want to read more.


Few neurological conditions are as complex and devastating as stroke, the second leading cause of death worldwide. Also called a brain attack, victims may suddenly experience paralysis, impaired speech, or loss of vision due to interruption of blood flow (ischemia) caused by thrombosis or embolism. Less frequently (<15%), strokes are caused by hemorrhage or cardiac arrest. On average, strokes in the USA strike once every 40 s and cause death every 4 min, with an estimated 41.6% death rate in 2007 (absolute numbers are likely to rise).

Among survivors, work capacity is compromised in 70% of victims, and 30% need assistance with self-care. Hence, the disease burden is great. The estimated cost for stroke is 73.7 billion dollars in 2010 (USA) and projected to be 1.52 trillion dollars in 2050 (in 2005 dollars) are spared, and the problem is global. For example, in the Russian Federation and China, the estimated death rates per 100,000 population are five to ten times higher than in the USA mankind. For the above considerations and more, there is a compelling need to accelerate efforts to interrogate the stroke process and define the links that exist with other conditions such as vascular and neurodegenerative dementia. It is also crucial to expand the narrow repertoire of therapeutic opportunities for these devastating conditions. To accomplish this, novel approaches are required that expand upon our evolving mechanistic understanding of the fundamentals of cell survival and death processes as well as tissue repair. The future depends upon how successful we are in deciphering these mechanisms and bringing clarity to the complex interactions between the multiplicity of cell and tissue types within brain with this knowledge and its successful therapeutic application, the field of stroke could be transformed.

In this spirit then, this brief review addresses selected issues fundamental to the science of ischemic stroke and vascular dementia. It begins with posing questions about stroke risk factors followed by a discussion of key cell and tissue mechanisms that render brain susceptible as well as tolerant to ischemic injury, including those promoting tissue protection and repair. The review ends by highlighting promising treatment strategies, inspired by these endogenous mechanisms, which present the opportunity to open new avenues in stroke therapy.

Selected section titles are here:
  • Parenchymal Failure: Why and How Does the Brain Die during Ischemia?
  • Salvageable versus Nonsalvageable Tissue: Salvageable Tissue Is the Target for Therapy
What Are the Prominent Mechanisms Leading to Cell and Tissue Demise?
  • Excitotoxicity
  • Calcium Dysregulation
  • Oxidative and Nitrosative Stress
  • Cortical Spreading Depolarizations
  • Inflammation
  • Necrosis, Necroptosis, and Autophagy: The Execution
  • What Causes the White Matter Damage Underlying VCI?
  • Why Does Stroke Increase the Risk of Dementia? This is worth reading although we need prevention.
  • How Does the Brain Repair Itself after Stroke?
  • Repair and Remodeling Processes after Stroke
  • Moving Forward: Charting a Course toward New Stroke Therapies
  • Additional Strategies for Repair and Recovery: Trophic Factors and Cell-Based Therapies

Someday I'll compare Dr. Moskowitz's theories with Dr. Clarkes Clarkes' stroke protocol. These two are the best I've seen and  wonder why there aren't more references to them. We have to get away from the only acute stroke medication is tPA. Everyone of your doctors should know about this, my opinion only.

See the original article:

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