Neurosciences research includes basic and clinical research studies in the Departments of Neurology, Neurosurgery, Eye Care Services, and the Imaging Program. The basic science programs are described below.
Department of Neurology: Stroke, Brain Injury and Neurodegenerative Diseases
Almost 800,000 Americans are diagnosed with stroke each year, and approximately one-third of them die. Health care costs for stroke exceed $60 billion per year. The Henry Ford Department of Neurology is internationally acclaimed for its research in stroke and neural injury and is the major driving force in the development of restorative neurology. The department has pioneered research in restorative therapy for the treatment of stroke, traumatic brain injury, peripheral neuropathy and neurodegenerative diseases using both cell-based and pharmacologic therapies, and has now again pioneered the use of exosomes, nanoparticle containers released by many cells, for the restorative treatment of neurological injury, and disease. The goal is to remodel the central nervous system (CNS) to compensate for the injured brain tissue. Researchers have also made major contributions to the development of neuroprototective agents, such as tissue plasminogen activator (tPA), and have been major innovators in the development and use of magnetic resonance imaging (MRI) for understanding neurological disease.
The department has a successful track record for obtaining NIH R01, R21, R43, R44, SBIR and STTR research grants, NIH program project grants and funding from other agencies and foundations. The work of researchers is shared in numerous annual publications.
Stroke, peripheral neuropathy, cognitive dysfunction, and use of exosomes in treatment of these diseases.
Department of Neurology research has shown that administration of exogenous cells, such as bone marrow mesenchymal cells, cord blood, cord tissue, placental tissue, brain progenitor cells and adult stem cells derived from various organs, greatly improves neurologic outcome after stroke and neural injury. Driving this functional improvement is the remodeling of the CNS, including the generation of new brain cells (neurogenesis), formation of new blood vessels (angiogenesis), and creation of new electrical connections (synaptogenesis). Several pharmacologic agents also have the capacity to enhance recovery from brain injury and may restructure the injured CNS. These include erythropoietin, carbamylated erythropoietin, statins, nitric oxide donors, thymosin-β4, agents that increase cGMP such as sildenafil and tadalafil, and agents that increase high-density lipoproteins such as niacin and Niaspan. Many of these agents are being tested in clinical trials and show promise for future therapy. In major new work, our department has demonstrated that exosomes mediate the therapeutic efficacy of stem cell therapy for the treatment of disease and injury. We have therefore employed exosomes from a variety of cells, as well as “designer” exosomes in which the microRNA content (regulates genetic translation) are modified for the efficacious treatment of neurological disease and injury, as well as for the treatment of certain cancers. This novel therapeutic approach has the potential to greatly impact patient care.
The department’s work in restorative neurology has spawned fundamental research into the mechanism by which cells or drugs induce brain plasticity. Researchers have published extensively on the molecular mechanisms controlling the generation of new brain cells and blood vessels. In addition, the coupling of neurogenesis and angiogenesis has been studied, demonstrating that restorative therapy establishes a remodeling microenvironment within the compromised tissue that stimulates structural changes and rewiring to compensate for injury. Moreover, this research has demonstrated that after injury to the brain, rewiring and other dramatic changes occur in the spinal cord and the contralateral brain hemisphere. The degree of rewiring strongly correlates with recovery of function, and treatments that stimulate functional recovery also lead to rewiring of the spinal cord and the contralateral hemisphere. Insight gained from stroke models is now being extended to studies of traumatic brain injury, multiple sclerosis and diabetes-induced peripheral neuropathy.
Researchers have recently started to focus on the diabetic brain. Diabetes is a major risk factor for stroke, and diabetic patients have more severe stroke and poor outcomes. The laboratory is investigating the bases for these adverse effects of diabetes on stroke and is actively developing new therapies to treat the diabetic stroke brain. In addition, we have a strong emphasis on how diabetes affects cognitive function, particularly during aging. We have therefore developed novel ways to predict cognitive impairment and have demonstrated that MRI of the glymphatic system (brain “waste” removal system can identify and predict cognitive and learning dysfunction. This technology is presently being applied to a variety of neural injury in our laboratory.
The Henry Ford Neurology research laboratory has initiated a major effort into investigating the role of microRNAs (miRNA) and epigenetics in neurological disease and recovery. Results show that miRNAs regulate apoptosis (cell death) and stimulate brain plasticity and neurogenesis. This pioneering work may have a major impact on the treatment of many neurological diseases. The research on miRNAs has also greatly impacted our pioneering work on the therapeutic role of exosomes in the treatment of disease. Our department was also the first to demonstrate the importance of miRNA in how tumors alter their microenvironment to promote cancer. We are actively employing exosomes and miRNA as monotherapy or in combination for the treatment of multiple cancers.
For more than 25 years Henry Ford neurologists have used magnetic resonance imaging (MRI) for understanding neurological disease. Researchers have developed novel approaches to the MRI measurement of brain plasticity, including angiogenesis and restructuring of white matter in the injured brain, which appears to play a pivotal role in functional recovery. Techniques have been developed to measure new vessels, vessel density and white-matter structure in human and animal brains. This has the potential to create new diagnostic and prognostic tools for management of neurological disease, so that MRI will greatly augment efforts in restorative neurology.
Neurology researchers maintain a highly productive research effort on developing neuroprotective agents, with a focus on the treatment of the elderly brain. Agents have been identified that act synergistically with tPA to greatly extend its therapeutic window, enhance its efficacy and reduce adverse effects.
Contact info: Michael Chopp, Ph.D.
Multiple Sclerosis (MS) research lab.
This laboratory has comprehensively shown the ameliorating role of AMPK (adenosine monophosphate activated kinase), a master regulator of metabolism, in the pathogenesis of MS using preclinical mouse models and its potential as a therapeutic target. While studying the role of AMPK in MS pathobiology, our laboratory was intrigued by the metabolism of the disease itself, which led us to investigate how the metabolism would be altered by MS disease progression. Using cutting edge technologies in the field of metabolism, we identified blood based multiple metabolic pathways in MS patients, that can be used to monitor MS progression and response to therapy. Additionally, we are currently testing the therapeutic targeting of these metabolic pathways in various MS mouse models. We believe that our approach of bed to bench and back to bed for translational purposes will not only provide a better understanding of the pathogenesis of MS, but will also allow for development of novel therapeutic modalities to cure this disease.
To achieve our goal, we are working on three major interconnected themes: 1) to understand the role of metabolic derangement in MS using preclinical mouse models and MS patients; 2) to identify biofluids based predictive metabolic biomarkers that can aid in monitoring and therapeutic response of MS patients and 3) defining the role of AMPK (adenosine monophosphate activated kinase), a master regulator of metabolism, in the pathogenesis of EAE/MS and its potential as a therapeutic target.
Contact info: S. Giri, Ph.D.
Clinical Research and Clinical Trials
The Department of Neurology actively conducts and supports clinical trials for a wide spectrum of neurological disorders encompassing research phases I, II, III and IV. The clinical trial programs are funded by various sources such as the NIH, foundations and industry sponsors, or are initiated by department investigators and funded by the NIH, industry sponsors and philanthropic donations.
As leaders in the field of cerebrovascular treatment and neurocritical care, Henry Ford’s cerebrovascular team participates in both sponsored and physician initiated studies. The team includes stroke neurologists, cerebrovascular neurosurgeons, neuroendovascular specialists and neurointensivists. Research studies include treatment for acute ischemic stroke, chronic ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage and coagulation reversal in intracranial bleeds.
Epilepsy research (make a link to https://www.henryford.com/services/epilepsy/research) at Henry Ford includes laboratory studies and clinical trials of drug therapies that reduce the incidence and intensity of seizures with fewer side effects; new technology that improves the complex diagnostic process to pinpoint the source of the electrical misfiring in the brain; and innovative techniques, such as neurostimulation devices, that help patients whose seizures are not controlled with medication and who cannot undergo surgery.
The Parkinson’s Disease and Movement Disorders Center at Henry Ford has three decades of experience in the medical and surgical management of Parkinson’s Disease, essential tremor, dystonia, ataxia and other neurologic disorders that affect normal movement of the body. Clinical trials offered by the Parkinson’s Disease and Movement Disorders Center have included development of new medications and the first successful gene therapy clinical trial for Parkinson’s Disease. The Center has participated in academic consortia for investigating neuroprotective treatments, improve rating scales and symptomatic therapies for tremor and dystonia in addition to Parkinson’s Disease research.
Henry Ford Neurology programs for neurodegenerative, neuromuscular and neuroimmunologic diseases are currently participating in studies for treatment of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), neuromyelitis optic/neuromyelitis optica spectrums disorder (NMO/NMOSD) and dementia. The MS clinic has participated in recent landmark studies for oral treatments of disease modifying therapies as well as the first treatment for primary progressive multiple sclerosis.
Henry Ford has 1 of 29 magnetoencephalography (MEG) brain imaging systems in the country. In addition to studies with epilepsy patients, physicians and neurology scientists are also using the MEG to explore dyslexia, language processing, tinnitus, sensory gating in schizophrenia and generalized dystonia.
Our speech and language pathologists are working on several projects that include determining the effects of deep brain stimulation frequency on swallowing in individuals with Parkinson’s Disease as well as self-perception of dysphagia and vocal handicap in Parkinson’s Disease. More recent research currently in the planning stages will focus on testing of novel electrostimulation devices to improve swallowing disorders after brain injury.
Department of Neurosurgery: traumatic brain injury, brain hemorrhage, and brain tumor research
- Traumatic Brain Injury
Contact info: Ye Xiong, Ph.D.
- Cerebrovascular Research
Contact info: Donald Seyfried, M.D.
- Hermelin Brain Tumor Center Research
Contact info: Steven Kalkanis, M.D., Chair, Department of Neurosurgery
The Bioinformatics Program within the Department of Neurosurgery is an active area of research focused on analysis of genomics and epigenomics data as well as bioinformatic tool development. Large-scale genomic data generation requires expertise in handling, processing and analyzing the data, and our team of bioinformaticians is skilled in areas of molecular biology, statistics and computation. Not only do we provide support for pre-processing large molecular datasets, but we strive to improve the quality of life of cancer patients by comparing the genomic alterations from cancer tumor cells to patients clinical data to achieve a better understanding of the relationship between clinical outcome and tumor biology. These efforts are aimed at identifying biological markers for prognostic applications, as well as identifying possible drug targets for improved therapy for patients suffering from complex diseases. Institutional projects utilizing our bioinformatics expertise include the Image Analysis Laboratory, Departments of Neurology and public Health Sciences, and collaborators within the Henry Ford Cancer Institute Molecular Tumor Board.
Contact info: Houtan Noushmehr, Ph.D.
A relatively new Neurosurgery research program involves the discipline of nanomedicine and drug delivery with noninvasive molecular imaging. Nanomedicine, carrying therapeutic payloads and delivered within close proximity of the tumor, can be designed to play a significant role in increasing treatment effectiveness while decreasing severity of side effects. Specifically, this lab work focuses on developing small-sized nanoparticles that can cross tumor blood brain barrier and target primary glioblastoma multiform (GBM) selectively. This work has been aided by the development of a series of new dendrimer-based multifunctional nanoparticles that are detected by standard MR relativity methods or new MRI methods based on Paramagnetic Chemical Exchange Saturation Transfer (PARACEST). With the development of small nano-sized molecular imaging agents that can target GBM selectively, primary GBM tumor selective drug delivery and imaging can be accomplished by using these dendrimer-based nanoparticles that possess long blood half-lives. We have reformulated promising anti-cancer drugs that failed to reach clinical trials, or failed in clinical trials due to toxicity or poor bioavailability. These reformulations have reproduced usable, safe therapies using nanoparticles. We have also used state-of-the-art MRI methods to study tumor progression and the early responses to chemotherapies in pre-clinical animal models.
Contact info: Meser Ali, Ph.D.
Department of Research: Imaging Research Program
Research studies in the Image Analysis Laboratory are directed towards extraction of quantitative information from medical images using image processing, analysis, and visualization techniques. The quantitative information can be used in basic research as well as clinical research and eventually for enhanced diagnosis, treatment planning, treatment evaluation, and prognosis of patients. These techniques are developed into software packages containing programs for 2D and 3D image registration, correction of artifacts and non-uniformities associated with the imaging experiment, image restoration and enhancement, feature extraction and image segmentation, 2D and 3D morphological image analysis, cluster analysis, statistical analysis associated with region of interest and volume of interest, and 2D and 3D visualization based upon surface and volume rendering techniques. The image processing techniques were initially designed for use with Magnetic Resonance Imaging (MRI). However, they have been modified for use with other imaging modalities such as X-ray Computed Tomography (CT), Ultrasound, Nuclear Medicine, and Light images. For example, they have been extended to automatically extract quantitative information of vascular structures from medical images. The methods have also been extended to analyze multi-modality data. The software programs are made available to the researchers within the institution and outside.
Institutional projects utilizing the image processing tools include: collaborative projects analyzing MRI studies of neurological lesions (brain tumors and multiple sclerosis), as well as neurological disorders such as Parkinson’s and epilepsy patients involving the Departments of Neurology, Neurosurgery, and Biostatistics, and collaborative projects analyzing images of stroke patients, involving the Departments of Neurology and Biostatistics.
Contact info: Hamid Soltanian-Zadeh, Ph.D.
Ophthalmology and Eye Care Services Research
Artificial vision research
For individuals blinded by some forms of retinal diseases, a microelectronic retinal prosthesis (a.k.a. bionic eye) could be a promising option to restore sight. Although a few bionic eye products are commercially available, the best performance is still far away from normal vision. To improve the quality of artificial vision, we are developing an innovative bionic eye using transdisciplinary approaches. With our engineering expertise, we are designing new electrodes for better visual acuity. Also, in the neuroscience perspective, we are studying fundamental neuronal mechanisms underlying retinal responses to electric stimulation for more natural artificial vision.
Contact info: Maesoon Im, Ph.D.
Macula degeneration and diabetic retinopathy research
My laboratory investigates the molecular mechanisms underlying retinal angiogenesis, particularly neovascularization in age-related macular degeneration (AMD) and diabetic retinopathy (DR). We use various approaches at different levels including cell culture of human retinal vascular endothelial cells, macrophages, and retinal pigment epithelial cells; animal models of genetic mutant mice with spontaneous subretinal neovascularization or laser-induced choroidal neovascularization, and streptozotocin (STZ)-induced diabetic model; as well as clinical data and human tissue samples. The goal is to search for new targets and develop novel treatment strategy to inhibit neovascularization in the retina. Our recent finding indicates that AMPK activator has potent anti-inflammatory and anti-angiogenic effects in vitro and in vivo. The focus is to identify the signaling pathways mediating such protective effects which could be used to treat retinal neovascularization in both AMD and DR.
Contact info: Xiao-xi Qiao, M.D.
Please see the list of Bioscientific Staff for contact info for all scientists in Neurosciences Research (Depts. of Neurology, Neurosurgery, Eye Care and Imaging).