Matrix fragments trigger fatal excitement

December 30, 2008

Shredded extracellular matrix (ECM) is toxic to neurons. Chen et al. reveal a new mechanism for how ECM demolition causes brain damage. The study will appear in the December 29, 2008 issue of The Journal of Cell Biology (www.jcb.org).

A stroke or head injury kills large numbers of neurons through a process called excitotoxicity. A surge of the neurotransmitter glutamate jolts receptors such as the kainate receptor and stimulates cell death. Enzymes add to the death toll by chopping up ECM near the injury site. How ECM breakdown takes out neurons was mysterious. The standard view was that neurons perished because they got separated from the ECM as it dissolved.

Chen et al. found otherwise when they engineered mice to lack the ECM component laminin in the hippocampus, a brain region often damaged by stroke or injury. If cells languished after parting from the ECM, the researchers reasoned that mice missing laminin would suffer more damage from excitotoxicity. But when excitotoxicity was spurred with an injection of kainate-a molecule that, like glutamate, activates the kainate receptor-the laminin-lacking mice showed less brain damage. After a dose of diced laminin, however, the mutant mice were vulnerable to kainate, indicating that the fragments are the culprit in cell death.

The researchers discovered that chopped-up ECM kills cells by ramping up production of one subunit of the kainate receptor, known as KA1. They speculate that hiking the amount of KA1 subunits might make the receptor more sensitive and thus more likely to trigger an overreaction by the cell.

Although drugs that obstruct the glutamate receptor slow brain cell death, they can lead to serious cognitive impairment and even coma. The study suggests that drugs that block KA1 might provide an alternative way to save brain cells after stroke or head trauma.

Rockefeller University Press

---

---

	Brain Damage: A Trip Through Hell by Broslin Press A short novel based on the screenplay for Brain Damage by Frank Henenlotter
	Mindstorms: Living with Traumatic Brain Injury by John W. Cassidy MD (Author), Lee Woodruff (Foreword) If your loved one has experienced a traumatic brain injury (TBI), you know that its effects can be devastating and often difficult to understand It may feel as if your world has shifted on its axis, and you’ll never get your bearings. Navigating your way through the morass of doctors, medical terms, and the healthcare system can be daunting, especially when you want only what’s best for the person you love. Dr. John Cassidy has devoted the past twenty-five years to helping families cope with traumatic brain injury; Mindstorms is his compassionate, comprehensive manual to demystifying this often frightening and life-changing condition.More than 6.3 million Americans live with a severe disability caused by a traumatic brain injury. In fact, because it’s so commonplace, but little...
	Brain Injury Survival Kit: 365 Tips, Tools and Tricks to Deal with Cognitive Function Loss by Cheryle Sullivan (Author) More and more Iraq war veterans are returning Stateside with brain injuries, drawing public attention to this condition. This practical, easy-to-use book gives brain injury survivors, their families, and their loved ones the strategies they need to boost brain function and live well. The book is a compendium of tips, techniques, and life-task shortcuts that author Cheryle Sullivan, a medical doctor and brain injury survivor, has compiled from personal experience. With a different tip for each day of the year, the book explains balancing a checkbook, using medication alarms, compensating for impaired memory, locating things that have been put away, finding the right word, concentration exercises, and much more. From basic principles to unique solutions for saving time and energy, this book...
	Murder on the Brain by Vanessa Gray Bartal Sabrina Farris likes her world in perfect order. Her cat is her only friend, and that's how she wants it. When she wakes up in a hospital, she discovers she was repeatedly hit in the head with a board and spent three weeks in a coma. Now an emotional wreck who can't stop crying, the only person in her new world is Maddox, the computer geek she loathed before she was attacked. Maddox is dealing with his own heartbreak. The last thing he needs is to try and put Sabrina the-dragon-lady Farris back together again, but she doesn't have anyone else. And Maddox begins to realize that this Sabrina is far different than she was before. Working together, they must figure out what in Sabrina's spotty memory led to her attack before her would-be killer strikes again. And along the way they...
	Damages and the reptilian brain: the 'reptilian brain' governs our survival responses. Tort 'reformers' have long used these responses dishonestly to ... misconduct.: An article from: Trial by David Ball (Author) This digital document is an article from Trial, published by American Association for Justice on September 1, 2009. The length of the article is 3093 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available immediately after purchase. You can view it with any web browser. Citation Details Title: Damages and the reptilian brain: the 'reptilian brain' governs our survival responses. Tort 'reformers' have long used these responses dishonestly to their advantage. This introduction to a new kind of advocacy will help you show jurors that the real danger is from the defendant's misconduct. Author: David Ball Publication: Trial (Magazine/Journal) Date: September 1, 2009 Publisher: American Association...
	The Brain That Changes Itself: Stories of Personal Triumph from the Frontiers of Brain Science by Norman Doidge (Author) An astonishing new science called "neuroplasticity" is overthrowing the centuries-old notion that the human brain is immutable. In this revolutionary look at the brain, psychiatrist and psychoanalyst Norman Doidge, M.D., provides an introduction to both the brilliant scientists championing neuroplasticity and the people whose lives they've transformed. From stroke patients learning to speak again to the remarkable case of a woman born with half a brain that rewired itself to work as a whole, The Brain That Changes Itself will permanently alter the way we look at our brains, human nature, and human potential.
	Dieting Causes Brain Damage: How to Lose Weight without Losing Your Mind by Bradley Trevor Greive (Author) "When you start a diet, the first thing you lose is your mind." --Bradley Trevor GreiveWith his trademark wit and humorous animal photographs, BTG explains that the true motivation for losing excess weight and keeping it off is purely to enjoy a better quality of life, to get the most out of our brief time on this earth.Dieting Causes Brain Damage identifies the most common causes of weight gain as well as the perils of extreme dieting, suggesting that the number-one lesson is to "Keep your mouth shut." This reduces the number of calories consumed and stops you from constantly whining and making excuses about your appearance.You don't need a PhD., millions of dollars, plastic surgery, a library of fad diet books, or a Day-Glo Lycra bodysuit to get into shape. Eating well, enjoying quality...
	Brain Injury Workbook: Exercises for Cognitive Rehabilitation by Trevor Powell (Author)
	Adam's Fall, Traumatic Brain Injury, the First 365 Days by Robert V. Bullough Jr. (Author) On a warm summer's evening, while riding his bicycle with his girlfriend down a gentle slope something inexplicable happened. Suddenly, Adam flew over his handle bars, bounced on the street, and crushed the back of his head. TBI--traumatic brain injury. In that moment, Adam's life and the life of his family changed forever. Like tens of thousands of other young people who probably rode their bikes that day, Adam was not wearing a helmet. Adam s Fall tells a very personal story of a young man's struggle to survive first while in prolonged coma and then to heal and to recover himself. It is a story of the heroic efforts of doctors, nurses and therapists who saved his life and of those who have since supported his healing. But mostly, it is a story of a family facing every parent's worst...
	Textbook of Traumatic Brain Injury by Jonathan M. Silver (Author), Thomas W. McAllister (Author), Stuart C. Yudofsky (Author) As soldiers and combat veterans have returned from the wars in Iraq and Afghanistan traumatic brain injury (TBI) has been identified as the signature injury of those wars. This new edition of Textbook of Traumatic Brain Injury has been thoroughly revised and updated from the 2005 first edition to reflect the exponential expansion of research and clinical data amassed in the intervening years. Each chapter was written and reviewed by the foremost authorities in neuropsychiatry, neurology, rehabilitation medicine, and the other specialties who assess, diagnose, and treat these patients. This textbook addresses epidemiology and pathophysiology; neuropsychiatric disorders; neuropsychiatric symptomatologies; special populations and issues; and treatment. Many of the foremost scholars and...