Release Date:  December 20, 2000

NOTICE:  NS-01-004

The National Institute of Neurological Disorders and Stroke (NINDS), NIH is 
seeking to identify sources that are interested to develop capabilities for 
characterizing gene expression patterns in the mammalian spinal cord following 
traumatic injury.

Introduction and Background

The NINDS is the lead government agency for funding of research on spinal cord 
injury (SCI).  Over 250,000 Americans are now paralyzed because of this 
condition and require specialized care and accommodation for everyday life.  
Since injury to the central nervous system (CNS) is a very complex phenomenon, 
research has often been limited to very specific molecules or mechanisms.  New 
technology in the area of molecular biology greatly increases the ability to 
investigate many changes in gene expression that might occur under this 
circumstance. Under this solicitation, projects will develop capabilities for 
characterizing gene expression patterns in the mammalian spinal cord following 
traumatic injury.  Research efforts will employ available neural tissue-specific 
and/or species-specific cDNA reagents and contemporary high throughput 
methodologies to quantify expression profiles of genes in acute and chronic 
phases of SCI.  Changes in expression will be characterized at the injury site 
as well as in areas of the cord rostral and caudal to the lesion site.  In 
addition, regions of brain that represent areas that project to or receive input 
from the spinal cord will also be evaluated for alterations in gene expression.  
The injury paradigm will utilize a well-characterized and justified rodent model 
of spinal cord trauma.  Since the CNS is a complex structure, patterns of 
expression of specific genes will be characterized by in situ hybridization.

Precise spatial-temporal expression of genes during development is critical for 
determining and maintaining the structure and function of the mammalian nervous 
system.  Numerous studies have identified factors that influence cell fate, 
expression of transmitters or growth factors, and guidance cues for axonal 
growth and dendritic arborization.  These changes may be highly relevant to the 
adult system after trauma or during disease processes.  It is not clear, 
however, to what extent such developmentally active molecules may be 
re-expressed after injury or during regeneration. Certainly, the expression of a 
multitude of genes and gene products associated with neuronal 
development--relating to neurite outgrowth, sprouting of fibers, cell 
survival--may be  affected and changed at critical times after injury.  For many 
years, researchers in the field of SCI have hypothesized that the failure of 
regeneration in the adult CNS is due primarily to the creation of a hostile 
"injury milieu"; might changes in expression patterns be correlated with an 
environment that prevents regeneration?

Analysis of changes in the multitude of proteins or mRNA patterns after injury 
is a daunting task.  Up until now, investigators have studied particular 
proteins (i.e., GAP-43) or classes of proteins (i.e., cytoskeletal proteins, 
trophic factors) in the hope of finding evidence for involvement in 
regenerative responses.  The development of new technologies to screen large 
numbers of genes or known sequences for expression after injury may focus the 
search for the critical elements in acute, sub-acute and chronic stages of 
injury.  Obviously, a complex condition such as SCI has critical temporal and 
anatomic parameters.  Prevention of outgrowth may occur at the injured axon tip 
or at the cell body.  Negative or positive factors are likely expressed from the 
time of the injury through several stages of recovery and stabilization.  
Therefore, analysis should include comparative time frames after trauma, and 
various parts of the neuroaxis that may react differently to the injury, 
regeneration or stabilization phases.

Goals of the Contract

1. Chips and micro-arrays made with cDNA from rodent nervous system (rat and 
mouse), and from whole animal (mouse) are available, and can be used to create 
maps of gene expression after SCI.  This contract will require the development 
and application of high-throughput approaches and technologies to quantify 
expression profiles of genes in rodent spinal cord following trauma.  The 
investigators who undertake the project must understand and have available a 
relevant rodent model of adult SCI.

2. There will be systematic comparisons of expression patterns for different 
regions of the cord, as well as at different timepoints following injury.  The 
technology will be applied to at least 6 time points representing acute (hours 
to days), subacute (days to weeks), and chronic (weeks to months) time windows 
to capture degenerative, regenerative, or stabilized patterns of reaction to 
injury.  In addition, several different areas will be sampled with respect to 
the injury site, including areas immediately rostral and caudal to the lesion as 
well as other segments (i.e., if lesion is at thoracic level sample cervical and 
lumbar as well).  In order to maximize the information gained from the studies, 
mRNA samples should be collected from relevant regions of the neuroaxis to 
sample cell bodies of projection neurons (i.e. cortex, brain stem, dorsal root 
ganglia), as well as local spinal cord circuits.

3. It is not the purpose of this contract to duplicate large scale production of 
specific chip or array technology at participating centers.  Technology should 
be available for use or purchase.

4. Investigators will be required to provide data on gene expression, 
localization of gene products or other results of the contract to NIH databases 
for dissemination.

Feedback is sought from the research community on the following:

o The selection of time points after injury;
o Levels of sampling;
o Selection of genes;
o Methodologies (i.e. SAGE, micro-arrays, etc.)
o Databasing requirements; and
o Possible animal models of SCI and control tissues

This Request for Information (RFI) is for information and planning purposes only 
and shall not be construed as a solicitation or as an obligation on the part of 
the Government.  The Government does not intend to award a contract on the basis 
of responses nor otherwise pay for the preparation of any information submitted 
or the Government's use of such information.  Acknowledgment of receipt of 
responses will not be made, nor will respondents be notified of the Government's 
evaluation of the information received.  However, should such a requirement 
materialize, no basis for claims against the Government shall arise as a result 
of a response to this request for information or the Government's use of such 
information as either part of our evaluation process or in developing 
specifications for any subsequent requirement.

Responses will be held in a confidential manner.  Any proprietary information 
should be so marked.  
All respondents are asked to indicate the type and size of your business 
organization, e.g., Large Business, Small Business, Hubzone Small Business, 
Small Disadvantaged Business, Women-Owned Business, 8(a), Historically Black 
College or University/Minority Institution (HBCU/MI), educational institution, 
profit/non-profit hospital, or other nonprofit organization.

Responses should be identified with NINDS RFI No. 01-004, and are due by January 
5, 2001.  Please submit three (3) copies of your response, not to exceed 5 
pages, to the attention of: Laurie A. Leonard, Contracting Officer, Contracts 
Management Branch, National Institute of Neurological Disorders and Stroke, NIH, 
6001 Executive Boulevard, Room 3287, MSC 9531, Bethesda, Maryland 20892-9531.  
Facsimile (301-402-4225) responses will also be accepted as long as they do not 
exceed 5 pages in length.  E-mail responses, sent to, will also 
be accepted. 

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