Cerebrovascular Biology and Neurovascular Unit
- Develop animal models expressing human gene mutations
- Use or develop models with cell specific manipulations: gene expression, caged compounds, etc.
- New imaging approaches in vivo and ex vivo
- Better access to human tissue
Hemostasis and Endothelial Cell Interaction
- Define responses of endothelial cells with a temporal relation to ischemia (pre, immediate post, and reparative phases)
- Understand disease modifiers in relation to ischemic susceptibility and intracerebral hemorrhage (e.g., Htn, age, DM)
- Develop and utilize selective models for studying stroke using reductionist and integrative approaches (e.g. cells, organ culture, animal models)
- Develop experimental platforms that link molecular to cellular to organ to human tissue systems that incorporate prevention of cell death and preservation of cell function.
- Develop region-specific NVU models and signals for gray and white matter.
- Link "omics"-derived biomarkers to actual pathophysiology and cross-talk targets.
- Dissect the transition zone from injury to repair.
- Invest in bioengineering
Neurovascular Protective Mechanisms
- Targeted financial support for development of animal models that focus on age, sex, background disease, long-term endpoints, and interventional devices.
- Support projects that highlight use of collaborative research with investigators outside our field and provide incentives for multidisciplinary research combinations.
Biology of Repair
- Support collaborative research (basic, preclinical, clinical) in post stroke recovery.
- Facilitate the movement of promising restorative therapies into the clinic.
- Investigate the impact of acute physiological management strategies (i.e. BP, temperature, glucose, seizures, osmolality, oxygen, vasospasm) on outcome
- Create a hemorrhagic stroke human tissue bank for basic science research focusing on blood-neuron-vessel interactions and vascular lesion formation.
- Develop better animal models which more closely resemble the human condition of hemorrhage and hemorrhagic transformation of ischemic stroke.
- Comprehensive, internet based, national outcome registry for ICH, SAH, and AVM.
Vascular Cognitive Impairment
- Experimental systems modeling human small vessel disease and VCI
- **Small- to moderate-scale human trials
- define high-risk populations
- validate radiographic and cognitive endpoints
- explore biomarkers
- identify candidate treatments
- Long-term prevention trials
- Establish a Stroke Research Study Group (SRSG) to define research priorities, characterize stroke phenotypes (quantitative endophenotypes, cognition, drug responsiveness, severity, recovery, etc), and rapidly execute large genetics studies in adult and pediatric stroke.
- Facilitate sample and data sharing, within and outside the SRSG using the NINDS Human Genetics Resource Center infrastructure.
- Promote the development of animal models to validate findings in human studies, going from association to causation.
- Support discovery-driven methodological approaches, like whole genome association, in the peer review of grant applications
- Harmonization criteria for phenotyping and data collection, presentation and storage for platform studies
- Training programs, including short courses at meetings, that bring together interdisciplinary audiences of biologists, bioinformaticians, clinician-investigators and trainees to address application of platform technologies to cerebrovascular disease
- Encourage (require?) consensus on data entry, format for NINDS-funded platform
- Richly phenotyped and characterized patient samples with attention to quantitative traits that will yield maximum information for exploratory analyses.
- Financial support to create infrastructure for neuroimaging research including dedicated cerebrovascular centers.
- Multicenter collaborations to conduct prospective hypothesis-driven studies and retrospective analyses of pooled datasets.
- Standardization of image analysis terminology and methodology (e.g. perfusion imaging) including support for NIH workshops.
- Development of a centralized, electronic neuroimaging repository to allow analysis of large, pooled datasets.
- Development of formal training programs (e.g. fellowships) for cerebrovascular imaging research.
- Integration of epi studies with common data elements, definitions, sharing plans, and central multi-dimensional repositories including imaging, blood and tissue
- Extension of epi studies to provide more robust longitudinal, secular, and temporal trend data
- Increase the opportunities for training in stroke epidemiology and clinical research methods and encourage multidisciplinary translational research collaborations to include epidemiologic expertise
- Target funding toward implementation research.
- Develop a two-step submission and review process for clinical trials and other large-scale grants with the first review focused on scientific and public health impact, and the second review after a collaborative effort to generate the optimal proposal.
- Increase interaction and collaboration between NINDS and potential partners, including CMS, FDA, insurers, and the pharmaceutical and device industries to identify synergies.
- Develop a program to support centers focused on multidisciplinary prevention research, modeled after the SPOTRIAS program.
Acute Stroke Treatment
- Waiver of Consent Workshop
- NINDS should take lead in coordinating NIH, FDA, and CMMS policies re: waiver in stroke trials
- ED Fellowship training in Vascular Neurology
- Endpoints Workshop
- Clinical and biomarker (serum, imaging)
- Analysis methods
- Methods for analysis of interaction among patient variables (R/G/age) and outcome
- Network of Interventionalists a la CRC or NETT to continue studies of endovascular revascularization
- Study utility of telemedicine for stroke trial enhancement
- RFA for studies of PSC and CSC efficacy and effectiveness
- Continue to require M/G enrollment reports. Consider gender as a stratification variable
- Get 50 to 80% of community medical centers certified as PSC
- Seek a funded CPT code for thrombolysis
- Support additional clinical trials in:
- acute ischemic and hemorrhagic stroke
- recovery and rehabilitation
- prevention of vascular-mediated cognitive decline
- pediatric stroke
- Address recruitment problems
- Improve trial efficiency:
- novel biomarkers / surrogate outcomes
- novel trial designs
- large, streamlined trials
Recovery and Rehabilitation
- RCT's of important parameters of conventional rehabilitation interventions:
- Timing, dosing schedule, half life of treatment effect, and differential effects of various training paradigms.
- Animal studies
- Validation as model of human recovery
- Key rehabilitation parameters
- Prolonging plastic period and reinstituting plasticity
- Develop interventions for chronically impaired persons.
- Phase II studies of cognitive rehabilitation strategies
- Studies that link neurologic impairment to disability and decreased social participation
Health Services Implementation
- Develop data dictionaries endorsed by key stakeholders, supported by easily adopted, clinically integrated, prospective data storage/shuttling systems.
- Go beyond "process" variables to include outcomes and patient physiologic/psychosocial variables that may contribute to long term results.
- Provider and system payment incentives (pay for performance), along with availability of cost-effective technology strategies.
- Public performance reporting if appropriate severity adjustment (not risk adjustment) measures can be assured.
- Use practice/professional organizations to support local development of cross-continuum relationships among providers of stroke care (reduce market competition and increase market cooperation).
- Grassroots initiatives to vertically integrate components of the health care system.
- Comprehensive Stroke Center certification with development of "hub" and "spoke" (Primary Stroke Centers) services.
- Increase expectations among certified/designated stroke centers for demonstrating community engagement:
- Shortened symptom onset to arrival times.
- Use of EMS for transport.
- Seamless transition to post-hospital care.
- Patients/families become advocates for their health (public mandate for improved access and evidence-based services).
- Understand the contribution of evidence-based, stroke care systems to reduction of stroke burden within the U.S. population.
- Effect of certified stroke centers on reduction of stroke burden;
- Identification of key characteristics supporting successful stroke centers/teams;
- Methods capable of galvanizing long-term community engagement in the prevention, early recognition, treatment and optimal societal reintegration of stroke. (e.g. educational strategies, public performance report cards / benchmarking, truthful public service announcements about patient outcomes associated with lack of treatment for stroke, etc.)
- Impact of innovative methods of stroke care delivery on access to medical services, cost and resource utilization, and ultimately patient physiologic and psychosocial outcomes. (e.g. telemedicine, e-ICU, use of APNs, etc.)