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This PAR replaces PAR-01-119. The NINDS is committed to identifying effective treatments for neurological disorders by supporting well-executed clinical trials. Before a definitive clinical trial can be designed, preliminary clinical studies are often required. The NINDS announces its interest in supporting studies required to obtain necessary information to establish clearly the clinical basis for proceeding to a definitive trial. The purpose of the PRELIMINARY INVESTIGATIONS LEADING TO OPTIMAL TRIALS IN NEUROLOGY grant (for brevity referred to as NINDS Preliminary Clinical Trials grant) is to obtain preliminary data and conduct studies to support the rationale for a subsequent definitive clinical trial of an intervention to treat or prevent neurological disease.

National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Drug Abuse (NIDA), the National Institute of Deafness and Other Communication Disorders (NIDCD) the National Institute of Alcohol Abuse and Alcoholism (NIAAA), and the National Institute on Aging (NIA) invite applications for studies on the cellular and molecular signaling between the local environment within organisms and stem and progenitor cells that are either introduced as transplants or are normally resident within host tissues and organs. The objective of this initiative is to promote a thorough exploration and characterization of the bi-directional communication between multipotent cells and the three-dimensional local milieu or niche that they encounter in vivo under normal and compromised states, such as with aging or following injury, disease or drug exposure. Of particular interest is the rigorous characterization of how interactions with localized cues in space and time regulate stem cell survival, migration, replication and 'plasticity' in the nervous system and other parts of the body. Projects that address comparisons between the responses of stem cells within niches in the developing and mature or aging nervous system in vivo, or in host microenvironments modified by injury, disease, or by exposure to drugs and alcohol would also be directly relevant to this Program Announcement with Set-aside (PAS), as are studies to compare different classes of stem cells or progeny at progressively more advanced stages of differentiation when placed in the same sites in vivo.

The National Institute of Neurological Disorders and Stroke (NINDS), along with the National Institute of Dental and Craniofacial Research (NIDCR), invite applications to advance our understanding of the neurobiology of persistent pain mediated by the trigeminal nerve and to develop effective therapeutic strategies to alleviate pain associated with disorders of myofascial, nervous, or skeletal tissues of the head and face, which are innervated by this nerve. The purpose of this initiative is to foster research that addresses the mechanisms of pain onset, chronic pain conditions, and responsiveness to pain therapy through novel basic and clinical research. Current knowledge of the neurobiology and neurochemistry of nociception, pain modulation and pain perception needs to be further developed and correlated with clinical manifestations of craniofacial pain to improve therapeutic strategies. This Program Announcement with Set-Aside funds (PAS) contributes to the goals of the NIH Pain Consortium, which is co- chaired by NINDS, NIDCR, and the National Institute of Nursing Research (NINR).

This Program Announcement (PA) replaces PA-00-105 and PA-00-106. Under this PA, the National Institute of Mental Health, National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, National Cancer Institute, National Institute of Child Health and Human Development, National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke invite research grant applications to expand basic and translational research on the processes and mechanisms involved in the experience and expression of emotion.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Eye Institute (NEI), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Nursing Research (NINR), National Institute of Child Health and Human Development (NICHD) invite the small business community to apply cutting edge technology to research to develop new approaches to prevent, treat, and cure type 1 diabetes and its complications. This RFA will utilize the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) mechanisms, but will be run in parallel with other requests for applications (RFAs) of similar scientific scope (DK- 03-015 for Innovative Partners and DK-03-001 for Bench to Bedside) that will utilize the traditional research project grant (R01), the exploratory/developmental grant (R21) or the exploratory/developmental grant phase II (R33) grant mechanisms.

The goal of this Program Announcement with set-aside funds (PAS) is to invite applications for studying the neurobiological and cerebrovascular mechanisms through which the neuroprotective blood-brain and blood-csf barriers function in the healthy and diseased adult, aged and pediatric brain. Blood-Brain Barrier (BBB) research embodies the true meaning of a "translational model" of neuroscience wherein breakthroughs in basic neuroscience are delivered to the clinic and require an agent delivery strategy and/or the ability to target specific areas of the brain. This PAS encourages studies focused on improving our understanding of the neuroprotective CNS barriers and enhancing the effectiveness of drug and gene delivery strategies for treatment of neurological diseases. Chief among the challenges to be addressed is the need to increase our knowledge about the molecular and cellular biology, cells of origin, gene and protein expression, and the regional differences of brain microvascular endothelial cells and pericytes and their interactions with adjacent brain cells.

Through this Program Announcement with set-aside funds (PAS), the National Institute of Neurological Disorders and Stroke invites applications to support research on reducing disparities in stroke through prevention of first and recurrent strokes among minority populations. For this PAS, minority group is defined by race/ethnicity, and includes African American, Hispanic American, Native American and Alaska Native, and Native Hawaiian and other Pacific Islanders. The purpose of the proposed grant program is to foster empirical research regarding interventions relating to the self-management of risk factors for first and recurrent stroke among members of minority populations.

The NINDS invites applications to validate animal models of pharmacoresistant epilepsy or intervention in the epileptogenic processes leading to chronic disease. The goal of this grant program is to validate proposed models of pharmacoresistant epilepsy and/or antiepileptogenic models for use in drug discovery. It will establish baseline data and introduce new methods for evaluating the therapeutic potential of novel compounds for the treatment of epilepsy.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute of Neurological Disorders and Stroke (NINDS) invite applications for basic and clinical studies to enhance understanding and prevention of hypoglycemia in patients with diabetes. Large clinical trials have demonstrated the efficacy of intensified glucose control in the prevention of the long-term vascular complication of diabetes. However, episodes of severe hypoglycemia may complicate intensified treatment and are often a major obstacle to the achievement of euglycemia in many patients. This RFA seeks basic and clinical studies to 1) enhance understanding of how the brain and other critical tissues sense and respond to hypoglycemia, 2) delineate the effects of hypoglycemia on brain function and 3) develop improved methodologies to prevent hypoglycemia, based on an understanding of physiological glucose sensing and counterregulation.

This is a reissuance of RFA DK-03-001. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Eye Institute (NEI), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Neurological Disorders and Stroke (NINDS), and the Office of Dietary Supplements (ODS) invite applications involving partnerships between clinical and basic biomedical researchers with the goal of translating advances in our understanding of the molecular basis of type 1 diabetes and its complications into new therapies for the prevention, treatment and cure of this disease. In these "bench to bedside" research partnerships, a team of clinical and basic scientists will conduct collaborative research that, if successful, will bring basic research advances from the laboratory to a point where a potential new therapy can be tested in patients or in preclinical studies in animal models.