AHA Grants Will Accelerate Search for New Stroke Therapies
Wednesday, June 27, 2018
A series of awards from the American Heart Association (AHA) to a team of researchers at the University of Rochester Medical Center (URMC) will focus on the development of new treatments to thwart the damage in the brain caused by stroke.
One of the research projects brings together experts in stroke, cardiovascular biology, platelet biology, and peptide chemistry. Marc Halterman, M.D., Ph.D., with the URMC Center for Neurotherapeutics Discovery, Scott Cameron, M.D., Ph.D., and Craig Morrell, D.V.M., Ph.D., with the URMC Aab Cardiovascular Research Institute, and Bradley Nilsson, Ph.D., with the University of Rochester Department of Chemistry will focus on the role that platelets play in acute brain injury and inflammation during stroke.
Platelets serve an important role in protecting against blood loss and repairing injured blood vessels. However, during a stroke the inflammatory properties of platelets can interfere with the restoration of blood flow once the clot in the brain is removed, particularly in micro-vessels, which can lead to permanent damage of brain tissue.
The research team will build synthetic peptides that activate platelets to study the phenomenon – which is called no-reflow – in an effort to identify specific switches within platelets that can be turned off and limit the cells’ inflammatory functions without blocking their ability to prevent bleeding.
Two AHA pre-doctoral fellowship awards Kathleen Gates and Jonathan Bartko in Halterman’s lab will support research that examines the link between an immune system response triggered by stroke in the lungs that can exacerbate damage in the brain and investigate the cellular mechanisms that determine whether or not brain cells die following stroke.
A final AHA award to the Halterman lab will seek to identify new drug targets by focusing on specific proteins activated during stroke that are suspected to play an important role in determining the survival of neurons.
Collectively, the AHA Collaborative Sciences Award, Pre-Doctoral, and Innovation awards represent $1.09 million in funding.Read More: AHA Grants Will Accelerate Search for New Stroke Therapies
Biological Sex Tweaks Nervous System Networks, Plays Role in Shaping Behavior
Thursday, March 8, 2018
By Mark Michaud
New research published today in the journal Current Biology demonstrates how biological sex can modify communication between nerve cells and generate different responses in males and females to the same stimulus. The findings could new shed light on the genetic underpinnings of sex differences in neural development, behavior, and susceptibility to diseases.
“While the nervous systems of males and females are virtually identical, we know that there is a sex bias in how many neurological diseases manifest themselves, that biological sex can influence behavior in animals, and that some of these differences are likely to be biologically driven,” said Douglas Portman, Ph.D., an associate professor in the Departments of Biomedical Genetics, Neuroscience, and the Center for Neurotherapeutics Discovery at the University of Rochester Medical Center (URMC) and lead author of the study. “This study demonstrates a connection between biological sex and the control and function of neural circuits and that these different sex-dependent configurations can modify behavior.”
The findings were made in experiments involving the nematode C. elegans, a microscopic roundworm that has long been used by researchers to understand fundamental mechanisms in biology. Many of the discoveries made using these worms apply throughout the animal kingdom and this research has led to a broader understanding of human biology. In fact, three Nobel Prizes in medicine and chemistry have been awarded for discoveries involving C. elegans.
The study focuses on the different behaviors of male and female worms. There are two sexes of C. elegans, males and hermaphrodites. Although the hermaphrodites are able to self-fertilize, they are also mating partners for males, and are considered to be modified females.
The behavior of C. elegans is driven by sensory cues, primarily smell and taste, which are used by the worms to navigate their environment and communicate with each other. Female worms secrete a pheromone that is known to attract males who are drawn by this signal in search of a mate. Other females, however, are repelled by the same pheromone. It is not entirely understood why, but scientists speculate that that the pheromone signals to females to avoid areas where there may be too much competition. Read More: Biological Sex Tweaks Nervous System Networks, Plays Role in Shaping Behavior
Lungs Mays Hold Key to Thwarting Brain Damage after a Stroke
Wednesday, January 31, 2018
By Mark Michaud
The harm caused by a stroke can be exacerbated when immune cells rush to the brain an inadvertently make the situation worse. Researchers at the University of Rochester Medical Center (URMC) are studying new ways to head off this second wave of brain damage by using the lungs to moderate the immune system’s response.
“It has become increasingly clear that lungs serve as an important regulator of the body’s immune system and could serve as a target for therapies that can mitigate the secondary damage that occurs in stroke,” said URMC neurologist Marc Halterman, M.D., Ph.D. “We are exploring a number of drugs that could help suppress the immune response during these non-infection events and provide protection to the brain and other organs.”
Halterman’s lab, which is part of the Center for NeuroTherapeutics Discovery, has been investigating domino effect that occurs after cardiac arrest. When blood circulation is interrupted, the integrity of our intestines becomes compromised, releasing bacteria that reside in the gut into the blood stream. This prompts a massive immune response which can cause systemic inflammation, making a bad situation worse.
While looking at mouse models of stroke, his lab observed that a similar phenomenon occurs. During a stroke blood vessels in the brain leak and the proteins that comprise the wreckage of damaged neurons and glia cells in the brain make their way into blood stream. The immune system, which is not used to seeing these proteins in circulation, responds to these damage-associated molecular patterns and ramps up to respond. Mobilized immune cells make their way into the brain and, finding no infection, nevertheless trigger inflammation and attack healthy tissue, compounding the damage.
The culprit in this system-wide immune response is neutrophils, a white cell in the blood system that serves as the shock troops of the body’s immune system. Because our entire blood supply constantly circulates through the lungs, the organ serves as an important way station for neutrophils. It is here that the cells are often primed and instructed to go search for new infections. The activated neutrophils can also cause inflammation in the lungs, which Halterman suspects may be mistakenly identified as post-stroke pneumonia. The damage caused by activated neutrophils can also spread to other organs including the kidneys, and liver.Read More: Lungs Mays Hold Key to Thwarting Brain Damage after a Stroke