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Spinal
Cord Injury
Spinal Cord Clinical Research
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Scientists in
the hospital's Center for Neural Recovery & Rehabilitation
Research have long been involved in basic research focused
on enabling the brain and spinal cord to recover from
traumatic injuries and illnesses. The CNRRR was established
as a neurobiological research center with the mission
of determining the causes that underlie neurological and
psychiatric diseases, and the reasons for cell death after
stroke or trauma, including spinal cord |
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injury. The scientist's approach is to research fundamental
mechanisms of the normal nervous system, in parallel
with clinical studies of disease and trauma. Together
these two avenues of research will be used to devise
and test new strategies for prevention, treatment, and
cure. The center currently holds over $1 million in
research funding from the National Institutes of Health.
Projects range from basic structure and function of
the nervous system to the mechanisms underlying spinal
cord injury and regeneration of nervous tissue.
Dr. Helen Scharfman is the Director of
the center. Other research scientists include Dr. Jeffrey
Goodman, Dr. Daniel McCloskey, Dr. Neil MacLusky, Nicholas
Makarenko, Kerry Stormes, Jane Schon, and Sudar Phani.
Students include Alon Mass, Nandini Nair, Andrew Ravenna,
and Katie Spero also participate in research.
Several major areas of research are ongoing.
The first is to clarify mechanisms underlying the regeneration
of the cord after injury. This work focuses on how new
neurons and glial cells are born, develop, migrate,
how they can be experimentally manipulated so that they
survive after injury and how can we ensure that they
restore the function of the injured nerve cells. |
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BDNF in the
Spinal Cord
Neuropeptide Y in SCI
Neuropeptide Y in Neurogenesis
Androgens and SCI
Publications
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BDNF
in the Spinal Cord
Alon Mass has examined the possibility that
a protein called BDNF would stimulate neurogenesis (the birth
of new nerve cells) in the cord, and recovery of function.
These studies used a transgenic mouse that
overexpresses the protein BDNF (brain-derived neurotrophic
factor). BDNF is a member of the neurotrophin family that
includes NGF (nerve growth factor ) and NT-3 (neurotrophin-3).
It is already known that BDNF influences spinal
cord motoneurons. It increases synaptic transmission. Experiments
by other research scientists in CNRRR have shown that the
same is true in the brain (Scharfman, 1997; Croll et al.,
1999; Scharfman et al., 1999, 2002), as have other laboratories
previously (Kang and Schuman, 1995, Patterson et al., 1996;
Korte et al., 1996; see Lu and Gottschalk, 1998 for review).
Mass found that BDNF overexpressing mice had
greater numbers of motoneurons and that the mice had altered
ability to walk (gait). The gait studies were conducted with
Dr. Susan Croll at CUNY, Queens College.
Taken together, the data suggest that BDNF
may be one of many factors that the body needs to sustain
a healthy spinal cord. Moreover, if it is increased, more
motoneurons may be possible. Thus, BDNF treatment after spinal
cord injury could potentially replenish lost motoneurons.
However, more research is needed because BDNF may also have
other effects that are not beneficial (Binder et al., 2000).
This research was presented at the Spinal Cord
Injury Symposium in New York in 2003. Alon Mass received a
semi-finalist award for the Intel Competition (2004) for his
research contribution. He is currently at Cornell University
and intends to continue his research endeavors. |
Neuropeptide
Y in Spinal Cord Injury
James Garrad has studied whether neuropeptide
Y (NPY) may be upregulated after injury. NPY is significant
because it increases the growth of new vessels and new neurons
in the brain, but whether it does so in the cord is currently
unclear.
The first studies have shown that injury to
the brain leads to upregulation of NPY in the spinal cord
at all levels. This is demonstrated by immunocytochemical
staining using an antibody to NPY. Experiments have shown
that new cells that are immunoreactive for NPY are also present
after injury. Double-labeling studies indicate that they may
be new glial cells, because the glial marker GFAP stains the
NPY-labeled cells. In normal cord some of these cells are
present in the dorsal columns.
These studies suggest that injury may naturally
lead to the entry or formation of new cells in the cord that
express the protein NPY. These cells may be glia, and help
rid the cord of toxins from injured cells. However, more research
is needed before the role of these cells, and of NPY, is clear.
James Garrad received a semi-finalist award
for this research, which was part of the Intel competition
in 2004. |
Neuropeptide
Y in Neurogenesis
Studies with our collaborators Dr. Liam Gray
(United Kingdom) have shown that neuropeptide Y (NPY) is a
peptide that is induced by BDNF and increases neurogenesis
(Howell et al 2003). Currently, Andrew Ravenna is examining
whether BDNF acts entirely by its ability to induce NPY. He
has found that the effects in the spinal cord that occurred
after BDNF levels were altered appear to be due to the NPY
levels that were also elevated. These studies suggest that
injury may naturally lead to the entry or formation of new
cells in the cord that develop as a function of a BDN-NPY
cascade. However, more research is needed before the role
of these cells, and of BDNF/NPY, are clear. |
Androgens
and SCI
Dr. Neil MacLusky has recently joined CNRRR
as an expert in neuroendocrinology. He has allowed CNRRR staff
to follow a potentially novel line of research that may lead
to better treatment of and even repair of the spinal cord.
He and his collaborators at Yale University have shown that
androgens can increase spine synapses in the brain of the
normal rat (Leranth et al 2004). We now are studying if the
same could be true in the spinal cord, and whether this might
be possible as a treatment to induce regeneration of nerve
cell network and function after injury. |
| Publications
Binder et al. 2001
Binder DK, Croll SD, Gall CM and Scharfman HE (2001) BDNF
and epilepsy: too much of a good thing? Trends Neurosci. 24:
47-53.
Croll et al. 1999
Croll SD, Suri C, Compton DL, Simmons MV, Yancopoulos GD,
Lindsay RM, Wiegand SJ and Scharfman HE (1999) Brain-derived
neurotrophic factor (BDNF) transgenic mice exhibit passive
avoidance deficits, increased seizure severity, and in vitro
hyperexcitability in the hippocampus and entorhinal cortex.
Neuroscience 93:1491-1506.
Kang and Schuman 1995
Long-lasting neurotrophin-induced enhancement of synaptic
transmission in the adult hippocampus.
Science. 1995 Mar 17;267(5204):1658-62.
Korte et al 1996
The involvement of brain-derived neurotrophic factor in hippocampal
long-term potentiation revealed by gene targeting experiments.
J Physiol Paris. 1996;90(3-4):157-64.
Leranth C, Hajszan T, MacLusky NJ.
Androgens increase spine synapse density in the CA1 hippocampal
subfield of ovariectomized female rats J Neurosci. 2004 Jan
14;24(2):495-9.
Lu and Gottschalk
Lu B, Gottschalk W (2000) Modulation of hippocampal synaptic
transmission and plasticity by neurotrophins. Prog Brain Res
128:231-241.
Patterson et al 1996
Recombinant BDNF rescues deficits in basal synaptic transmission
and hippocampal LTP in BDNF knockout mice.
Neuron. 1996 Jun;16(6):1137-45.
Scharfman 1997
Scharfman HE (1997) Hyperexcitability in combined entorhinal/hippocampal
slices of adult rat after exposure to brain derived neurotrophic
factor. J. Neurophysiol. 78:1082-1095.
Scharfman et al 1999
Scharfman HE, Goodman JH and Sollas AL (1999) Actions of BDNF
in slices from rats with spontaneous seizures and mossy fiber
sprouting in the dentate gyrus. J. Neurosci. 19:5619-5631.
Scharfman et al 2000
Scharfman HE, Goodman JH and Sollas AL (2000) Granule-like
neurons at the hilar/CA3 border after status epilepticus and
their synchrony with area CA3 pyramidal cells: functional
implications of seizure-induced neurogenesis. J. Neurosci.
20:6144-6158.
Scharfman et al 2002
Scharfman HE, Goodman, JH, Sollas AL and Croll SD (2002) Spontaneous
limbic seizures after intrahippocampal infusion of brain-derived
neurotrophic factor (BDNF). Exp. Neurol. 174:201-214.
Howell O.W., Scharfman H.E., Beck-Sickinger
A.G., Herzog H.H. and Gray W.P. (2003)
Neuropeptide Y is neuroproliferative for hippocampal stem
cells and neuroblasts. J. Neurochem. 86:646-59. |
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