Exosomes as potential biomarkers of radiation exposure

Exosomes = potential biomarkers of radiation in the Read more

Before the cardiologist goes nuclear w/ stress #AHA17

Measuring troponin in CAD patients before embarking on stress testing may provide Read more

Virus hunting season open

Previously unknown viruses, identified by Winship + UCSF scientists, come from a patient with a melanoma that had metastasized to the Read more

Robert Gross

Cell therapy clinical trial in stroke

Emory neurosurgeon Robert Gross was recently quoted in a Tennessee newspaper article about a clinical trial of cell therapy for stroke. He used cautionary language to set expectations.

“We’re still in the very early exploratory phases of this type of work,” Gross told the Chattanooga Times Free Press. “In these cases, a significant area of the brain has been damaged, and simply putting a deposit of undifferentiated cells into the brain and magically thinking they will rewire the brain as good as new is naive. None of us think that.”

A more preliminary study (just 18 patients) using the same approach at Stanford and University of Pittsburgh was published this summer in Stroke, which says it was the “first reported intracerebral stem cell transplant study for stroke in North America.” The San Diego Union Tribune made an effort to be balanced in how the results were described:

Stroke patients who received genetically modified stem cells significantly recovered their mobility… Outcomes varied, but more than a third experienced significant benefit.

The newspaper articles made us curious about what these cells actually are. They’re mesenchymal stromal cells, engineered with an extra modified Notch gene. That extra gene drives them to make more supportive factors for neurons, but it doesn’t turn them into neurons. Read more

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Tools for illuminating brain function make their own light

Optogenetics has taken neuroscience by storm in recent years because the technique allows scientists to study the brain conveniently in animals, activating or inhibiting selected groups of neurons at the flip of a switch.  Most often, scientists use a fiber optic cable to deliver light into the brain.

Researchers at Emory and Georgia Tech have developed tools that could allow neuroscientists to put aside the fiber optic cable, and use a glowing protein from coral as the light source instead.

Biomedical engineering student Jack Tung and neurosurgeon/neuroscientist Robert Gross, MD, PhD have dubbed these tools “inhibitory luminopsins” because they inhibit neuronal activity both in response to light and to a chemical supplied from outside.

A demonstration of the luminopsins’ capabilities was published September 24 in the journal Scientific Reports.  The authors show that these tools enabled them to modulate neuronal firing, both in culture and in vivo, and modify the behavior of live animals.

Tung and Gross are now using inhibitory luminopsins to study ways to halt or prevent seizure activity in animals.

“We think that this approach may be particularly useful for modeling treatments for generalized seizures and seizures that involve multiple areas of the brain,” Tung says. “We’re also working on making luminopsins responsive to seizure activity: turning on the light only when it is needed, in a closed-loop feedback controlled fashion.” More here. Read more

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The buzz of consciousness and how seizures disrupt it

These days, it sounds a bit old-fashioned to ask the question: “Where is consciousness located in the brain?” The prevailing thinking is that consciousness lives in the network, rather than in one particular place. Still, neuroscientists sometimes get an intriguing glimpse of a critical link in the network.

A recent paper in the journal Epilepsy & Behavior describes an epilepsy patient who had electrodes implanted within her brain at Emory University Hospital, because neurologists wanted to understand where her seizures were coming from and plan possible surgery. Medication had not controlled her seizures and previous surgery elsewhere had not either.

ElectrodesSmaller

MRI showing electrode placement. Yellow outline indicates the location of the caudate and thalamus. Image from Leeman-Markowsi et al, Epilepsy & Behavior (2015).

During intracranial EEG monitoring, implanted electrodes detected a pattern of signals coming from one part of the thalamus, a central region of the brain. The pattern was present when the patient was conscious, and then stopped as soon as seizure activity made her lose awareness.

The pattern of signals had a characteristic frequency – around 35 times per second – so it helps to think of the signal as an auditory tone. Lead author Beth Leeman-Markowski, director of EUH’s Epilepsy Monitoring Unit at the time when the patient was evaluated, describes the signal as a “buzz.”

“That buzz has something to do with maintenance of consciousness,” she says. Read more

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Brain surgery with a light touch

As part of reporting on neurosurgeon Robert Gross’s work with patients who have drug-resistant epilepsy, I interviewed a remarkable woman, Barbara Olds. She had laser ablation surgery for temporal lobe epilepsy in 2012, which drastically reduced her seizures and relieved her epilepsy-associated depression.

Emory Medicine’s editor decided to focus on deep brain stimulation, rather than ablative surgery, so Ms. Olds’ experiences were not part of the magazine feature. Still, talking with her highlighted some interesting questions for me.

Emory neuropsychologist Dan Drane, who probes the effects of epilepsy surgery on memory and language abilities, had identified Olds as a good example of how the more precise stereotactic laser ablation procedure pioneered by Gross can preserve those cognitive functions, in contrast to an open resection. Read more

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DBS for drug-resistant epilepsy

Space considerations in print forced us to slim down the feature on deep brain stimulation for drug resistant epilepsy, which appears in the Spring 2015 issue of Emory Medicine. While I encourage you to please read our story profiling playwright Paula Moreland, here are some take-away points:

*Surgery is a viable option for many patients with drug-resistant epilepsy, but not all of them, because the regions of the brain where the seizures start can have important functions. (Look for an upcoming post describing a patient I met for whom the surgical option was helpful.)

*Deep brain stimulation can reduce seizure frequency and improve quality of life for patients with drug-resistant epilepsy.

*In the large clinical trials on deep brain stimulation for epilepsy that have been run so far (SANTE and RNS), most participants do not see their seizures eliminated. Ms. Moreland is an exception.  Read more

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Recording seizures from within the brain

To go along with the (new) Spring 2015 Emory Medicine magazine set of features on deep brain stimulation for depression, movement disorders and epilepsy, here is a fascinating 2013 case report from Emory neurosurgeon Robert Gross and colleagues. The first author is electrical engineer Otis Smart.

It’s an example of the kinds of insights that can be obtained from implantable electrical stimulation devices, which can record signals from seizures inside the brain over long periods of time (more than a year).

As the authors write, “the technology can record brain activity while the patient is in a more naturalistic environment than a hospital, becoming an invasive ambulatory EEG.” Read more

Posted on by Quinn Eastman in Neuro 1 Comment

Lab Land looking back: Top ten themes for 2014

It is a privilege to work at Emory and learn about and report on so much quality biomedical research. I started to make a top 10 for 2014 and had too many favorites. After diverting some of these topics into the 2015 crystal ball, I corralled them into themes.
1. Cardiac cell therapy
PreSERVE AMI clinical trial led by cardiologist Arshed Quyyumi. Emory investigators developing a variety of approaches to cardiac cell therapy.
2. Mobilizing the body’s own regenerative potential
Ahsan Husain’s work on how young hearts grow. Shan Ping Yu’s lab using parathyroid hormone bone drug to mobilize cells for stroke treatment.
3. Epigenetics
Many colors in the epigenetic palette (hydroxymethylation). Valproate – epigenetic solvent (anti-seizure –> anti-cancer). Methylation in atherosclerosis model (Hanjoong Jo). How to write conservatively about epigenetics and epigenomics.
4. Parkinson’s disease therapeutic strategies
Container Store (Gary Miller, better packaging for dopamine could avoid stress to neurons).
Anti-inflammatory (Malu Tansey, anti-TNF decoy can pass blood-brain barrier).
5. Personal genomics/exome sequencing
Rare disease diagnosis featured in the New Yorker. Threepart series on patient with GRIN2A mutation.
6. Neurosurgeons, like Emory’s Robert Gross and Costas Hadjpanayis, do amazing things
7. Fun vs no fun
Fun = writing about Omar from The Wire in the context of drug discovery.
No fun (but deeply moving) = talking with patients fighting glioblastoma.
8. The hypersomnia field is waking up
Our Web expert tells me this was Lab Land’s most widely read post last year.
9. Fine-tuning approaches to cancer
Image guided cancer surgery (Shuming Nie/David Kooby). Cancer immunotherapy chimera (Jacques Galipeau). Fine tuning old school chemo drug cisplatin (Paul Doetsch)
10. Tie between fructose effects on adolescent brain (Constance Harrell/Gretchen Neigh) and flu immunology (embrace the unfamiliar! Ali Ellebedy/Rafi Ahmed)
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Monitoring the brain’s temperature

It’s been a little while since we had an Intriguing Image. This video illustrates a surgical technique for the treatment of medication-resistant temporal lobe epilepsy.

In this procedure, which is designed to minimize cognitive side effects, the surgeon carefully uses a laser probe to heat and ablate the regions of the brain doctors think are important for seizures. Magnetic resonance imaging allows the temperature in the brain to be precisely monitored. The video was provided by Robert Gross, MD, PhD, and accompanies an upcoming paper in the journal Neurosurgery. More discussion of this procedure here and here.

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The classic epilepsy surgery case

The epilepsy patient Henry Molaison, known for most of the 20th century as H.M., is one of the most famous in neuroscience. His case played an important role in telling scientists about structures of the brain that are important for forming short-term and long-term memories.

To control H.M.’s epilepsy, neurosurgeon William Scoville http://www.raybandasoleit.com/ removed much of the hippocampi, amygdalae and nearby regions on both sides of his brain. After the surgery, H.M. suffered from severe anterograde amnesia, meaning that he could not commit new events to explicit memory. However, other forms of his memory were intact, such as short-term working memory and motor skills.Henry_Gustav_1

This classic case helps us understand the advances that neurosurgeons at Emory are achieving today. The surgeries now used to treat some medication-resistant forms of epilepsy are similar to what was performed on H.M., although they are considerably less drastic. Usually tissue on only one side of the brain is removed. Still, there can be cognitive side effects: loss of visual or verbal memory abilities, and deficiencies in the ability to name or recognize objects, places or people.

Neurosurgeon Robert Gross has been a pioneer in testing a more precise procedure, selective laser amygdalohippocampotomy (SLAH), which appears to control seizures while having less severe side effects. Neuropsychologist Daniel Drane reported at the recent American Epilepsy Society meeting on outcomes from a series of SLAH surgeries performed at Emory.

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