NEURAL REGENERATION AND PLASTICITY AFTER SPINAL CORD INJURY

NIH GUIDE, Volume 21, Number 41, November 13, 1992



PA:  PA-93-018



P.T. 34



Keywords:

  Injury 

  Nervous System 

  Neuroscience 

  Gene Products 



National Institute of Neurological Disorders and Stroke



PURPOSE



The Division of Stroke and Trauma (DST), National Institute of

Neurological Disorders and Stroke (NINDS), invites applications for

support of research that will increase our knowledge of the mechanisms

underlying the neuronal regeneration and plasticity that can follow

spinal cord injury.



HEALTHY PEOPLE 2000



The Public Health Service (PHS) is committed to achieving the health

promotion and disease prevention objectives of "Healthy People 2000,"

a PHS-led national activity for setting priority areas.  This Program

Announcement (PA), Neural Regeneration and Plasticity after Spinal Cord

Trauma, is related to the priority area of unintentional injuries:

spinal cord injury.  Potential applicants may obtain a copy of "Healthy

People 2000" (Full Report:  Stock No. 017-001-00474-0) or "Healthy

People 2000" (Summary Report:  Stock No. 017-001-00473-1) through the

Superintendent of Documents, Government Printing Office, Washington, DC

20402-9325 (telephone 202-783-3238).



ELIGIBILITY REQUIREMENTS



Applications may be submitted by foreign and domestic institutions,

for-profit and non-profit organizations, public and private, such as

universities, colleges, hospitals, laboratories, units of State and

local governments, and eligible agencies of the Federal government.

Applications from minority institutions, minority individuals, and

women are particularly encouraged.



MECHANISMS OF SUPPORT



The support mechanism for grants in this area will be the traditional

investigator-initiated research project grant (R01).  The Principal

Investigator will plan, direct, and, along with any co-investigators,

perform the research.  Applicants are encouraged to contact the NINDS

representative listed below as early as possible in the planning

stages.



RESEARCH OBJECTIVES



Background



Injury to the spinal cord tragically affects hundreds of thousands of

victims in the United States, with approximately 10,000 new traumatic

injuries each year.  Early treatment and improved hospital care have

increased survival, but at great cost.  The estimated yearly cost of

long term, specialized care for paralyzed patients exceeds $2 billion.

The personal costs to patients and their families is beyond

calculation: planned education, career, marriage, and independence are

interrupted and often never regained.



The spinal cord, as part of the central nervous system (CNS),

coordinates movement and sensation for the entire body below the head.

Specialized cell populations within the cord are the substrates for

these functions.  Large motoneurons extend long axons peripherally to

innervate skeletal muscle.  Extensive arborizations of these

motoneurons receive information via descending tracts from the brain.

The long fibers of dorsal root ganglion cells connect peripheral

sensory receptors to spinal interneurons, to motoneurons, and to brain

centers.  This complex neuronal circuitry of the spinal cord is

supported by the glia of the CNS.  Radial glia enclose the cord like

the rim and spokes of a wheel, defining compartments for ascending and

descending fiber systems.  Astrocytes contribute to the blood-spinal

cord barrier and provide a wide variety of support functions.

Oligodendrocytes myelinate axons.



Traumatic injury disrupts all of these cell types and changes their

functions.  Axons degenerate, neurons die, astrocytes proliferate and

become reactive, radial glia enclose large cysts, and oligodendrocytes

cannot remyelinate damaged areas.  The anatomy of an injured spinal

cord shows profound pathology, but also reveals the sprouting of

uninjured fibers, the regeneration of damaged populations, the

reorganization of glia, and clearing away of debris.



Enhancement of these beginnings of regeneration and reorganization is

necessary.  Several trophic factors are known to affect survival of

neurons and extension of neurites.  Likewise, naturally occurring

substances may enhance supportive glial functions.  Components of the

extracellular matrix can support the growth of axons.  The growing

knowledge of cellular mechanisms of repair within the injured spinal

cord offers the hope of treatment for this devastating disorder.



Research Goals and Scope



Examples of investigator-initiated research grant applications for

basic, applied, and clinical studies related to the understanding and

enhancement of regeneration in the injured spinal cord may include, but

should not necessarily be limited to:



o  identification of the tissues, cells, and substrates critical to the

regenerative process;



o  behavioral, chemical, functional, and structural correlates of

restored or remodeled neural circuits;



o  gene and protein expression in neurons and support cells during

regeneration;



o  development of cellular transplants to augment or support

regeneration, restore lost function, or replace damaged cells;



o  immune responses to implants of neural tissues, cell lines, or

cellular products; and



o  pharmacological or biochemical approaches to prolong or enhance

regeneration.



Applicants are encouraged to develop and use new or refined

methodologies, instrumentation, and procedures that will reveal

mechanistic details of the regenerative process.  Basic, applied, or

clinical studies on interventions or manipulations to improve regrowth

of fibers, prevent pathophysiological changes, or aid in functional

recovery are welcome.



POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL

RESEARCH STUDY POPULATIONS



NIH policy is that applicants for NIH clinical research grants and

cooperative agreements will be required to include minorities and women

in study populations so that research findings can be of benefit to all

persons at risk of the disease, disorder, or condition under study;

special emphasis should be placed on the need for inclusion of

minorities and women in studies of diseases, disorders, and conditions

that disproportionately affect them.  This policy is intended to apply

to males and females of all ages.  If women or minorities are excluded

or inadequately represented in clinical research, particularly in

proposed population-based studies, a clear compelling rationale should

be provided.



The composition of the proposed study population must be described in

terms of gender and racial or ethnic group.  In addition, gender and

racial or ethnic issues should be addressed in developing a research

design and sample size appropriate for the scientific objectives of the

study.  This information should be included in the form PHS 398 in

Sections 1-4 of the Research Plan AND summarized in Section 5, Human

Subjects.  Applicants are urged to assess carefully the feasibility of

including the broadest possible representation of minority groups;

however, the NIH recognizes that it may not be feasible or appropriate

in all research projects to include representation of the full array of

Unites States racial or ethnic minority populations:  Native Americans

(including American Indians or Alaska Natives), Asian or Pacific

Islanders, Blacks, and Hispanics).  The rationale for studies on single

minority population groups should be provided.



For the purpose of this policy, clinical research includes human

biomedical and behavioral studies of etiology, epidemiology, prevention

(and prevention strategies), diagnosis, or treatment of diseases,

disorders, or conditions, including, but not limited to, clinical

trials.



The usual NIH policies concerning research on human subjects also

apply.  Basic research or clinical studies in which human tissues

cannot be identified or linked to individuals are excluded; however,

every effort should be made to include human tissues from women and

racial or ethnic minorities when it is important to apply the results

of the study broadly.  This directive should be addressed by

applicants.



For foreign awards, the policy on inclusion of women applies fully.

Since the definition of minority differs in other countries, the

applicant must discuss the relevance of research involving foreign

population groups to the United States' populations, including

minorities.



If the required information is not contained within the application,

the review will be deferred until the information is provided.



Peer reviewers will address specifically whether the research plan in

the application conforms to these policies.  If the representation of

women or minorities in a study design is inadequate to answer the

scientific question(s) addressed AND the justification for the selected

study population is inadequate, it will be considered a scientific

weakness or deficiency in the study design and will be reflected in

assigning the priority score to the application.



All applications for clinical research submitted to the NIH are

required to address these policies.  NIH funding components will not

award grants or cooperative agreements that do not comply with these

policies.



APPLICATION PROCEDURES



Applications are to be submitted on the grant application form PHS 398

(rev. 9/91) according to the instructions included in the application

package.  These application packages are available at the business

offices of most institutions eligible to receive Federal grants and

from the Office of Grants Inquiries, Division of Research Grants,

National Institutes of Health, Westwood Building, Room 449, Bethesda,

MD 20892, telephone 301/496-7441.



Receipt dates for new research project grant applications (R01) are

February 1, June 1, and October 1.



On page 1 of form PHS 398, check "yes" in Item 2a, enter the number of

this Program Announcement in the space provided, and provide the name

of this Program Announcement, Neural Regeneration and Plasticity after

Spinal Cord Injury in the blank space labeled "Title."



Use the mailing label provided in the application package to mail the

signed original and five exact copies of it to:



Division of Research Grants.

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**



REVIEW CONSIDERATIONS



Applications will be reviewed for scientific and technical merit by an

appropriate study section in the Division of Research Grants.  The

second level of review will be by the appropriate national advisory

council.  The standard review criteria will be used to assess the

scientific merit of applications.



AWARD CRITERIA



Applications will compete for available funds with other applications

assigned to an Institute or Center.  The following will be considered

when making funding decisions:



o  quality of the proposed projects as determined by peer review

o  availability of funds

o  program balance among research areas.



INQUIRIES



Questions concerning scientific aspects of this Program Announcement

may be addressed to:



Dr. Mary Ellen Michel

Division of Stroke and Trauma

National Institute of Neurological Disorders and Stroke

Federal Building, Room 8A13

Bethesda, MD  20892

Telephone:  (301) 496-4226

FAX:  (301) 480-1080



Questions concerning fiscal aspects of this Program Announcement may be

addressed to:



Mr. King P. Bond, Jr.

Division of Extramural Activities

National Institute of Neurological Disorders and Stroke

Federal Building, Room 1004

Bethesda, MD  20892

Telephone:  (301) 496-9231

FAX:  (301) 402-0219



AUTHORITY AND REGULATIONS



This program is described in the Catalogue of Federal Domestic

Assistance No. 93.853, Clinical Research Related to Neurological

Disorders, and No. 93.854, Biological Basis Research in the

Neurosciences.  Grants will be awarded under the authority of the

Public Health Service Act, Title IV, Section 301 (Public Law 78-410, as

amended: 42 USC 241) and administered under PHS grants policies and

Federal Regulations 42 CFR Part 52 and 45 CFR 74.  This program is not

subject to Health Services Agency Review of the intergovernmental

review requirements of Executive Order 12372.



.

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