Abstract
We previously showed that Nuclear Factor κB (NF-κB) inactivation in astrocytes leads to improved functional recovery following spinal cord injury (SCI). This correlated with reduced expression of pro-inflammatory mediators and chondroitin sulfate proteoglycans, and increased white matter preservation. Hence we hypothesized that inactivation of astrocytic NF-κB would create a more permissive environment for axonal sprouting and regeneration. We induced both contusive and complete transection SCI in GFAP-Inhibitor of κB-dominant negative (GFAP-IκBα-dn) and wild-type (WT) mice and performed retrograde [fluorogold (FG)] and anterograde [biotinylated dextran amine (BDA)] tracing 8 weeks after injury. Following contusive SCI, more FG-labeled cells were found in motor cortex, reticular formation, and raphe nuclei of transgenic mice. Spared and sprouting BDA-positive corticospinal axons were found caudal to the lesion in GFAP-IκBα-dn mice. Higher numbers of FG-labeled neurons were detected immediately rostral to the lesion in GFAP-IκBα-dn mice, accompanied by increased expression of synaptic and axonal growth-associated molecules. After transection, however, no FG-labeled neurons or BDA-filled axons were found rostral and caudal to the lesion, respectively, in either genotype. These data demonstrated that inhibiting astroglial NF-κB resulted in a growth-supporting terrain promoting sparing and sprouting, rather than regeneration, of supraspinal and propriospinal circuitries essential for locomotion, hence contributing to the improved functional recovery observed after SCI in GFAP-IκBα-dn mice.
| Original language | English |
|---|---|
| Pages (from-to) | 765-778 |
| Number of pages | 14 |
| Journal | Journal of Neurochemistry |
| Volume | 110 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 1 2009 |
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Keywords
- Anterograde tracing
- Astrocytes
- GAP-43
- Neuroprotection
- Retrograde tracing
- Transgenic mice
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience
Cite this
Transgenic inhibition of astroglial NF-κB leads to increased axonal sparing and sprouting following spinal cord injury. / Brambilla, Roberta; Hurtado, Andres; Persaud, Trikaldarshi; Esham, Kim; Pearse, Damien D; Oudega, Martin; Bethea, John R.
In: Journal of Neurochemistry, Vol. 110, No. 2, 01.07.2009, p. 765-778.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transgenic inhibition of astroglial NF-κB leads to increased axonal sparing and sprouting following spinal cord injury
AU - Brambilla, Roberta
AU - Hurtado, Andres
AU - Persaud, Trikaldarshi
AU - Esham, Kim
AU - Pearse, Damien D
AU - Oudega, Martin
AU - Bethea, John R.
PY - 2009/7/1
Y1 - 2009/7/1
N2 - We previously showed that Nuclear Factor κB (NF-κB) inactivation in astrocytes leads to improved functional recovery following spinal cord injury (SCI). This correlated with reduced expression of pro-inflammatory mediators and chondroitin sulfate proteoglycans, and increased white matter preservation. Hence we hypothesized that inactivation of astrocytic NF-κB would create a more permissive environment for axonal sprouting and regeneration. We induced both contusive and complete transection SCI in GFAP-Inhibitor of κB-dominant negative (GFAP-IκBα-dn) and wild-type (WT) mice and performed retrograde [fluorogold (FG)] and anterograde [biotinylated dextran amine (BDA)] tracing 8 weeks after injury. Following contusive SCI, more FG-labeled cells were found in motor cortex, reticular formation, and raphe nuclei of transgenic mice. Spared and sprouting BDA-positive corticospinal axons were found caudal to the lesion in GFAP-IκBα-dn mice. Higher numbers of FG-labeled neurons were detected immediately rostral to the lesion in GFAP-IκBα-dn mice, accompanied by increased expression of synaptic and axonal growth-associated molecules. After transection, however, no FG-labeled neurons or BDA-filled axons were found rostral and caudal to the lesion, respectively, in either genotype. These data demonstrated that inhibiting astroglial NF-κB resulted in a growth-supporting terrain promoting sparing and sprouting, rather than regeneration, of supraspinal and propriospinal circuitries essential for locomotion, hence contributing to the improved functional recovery observed after SCI in GFAP-IκBα-dn mice.
AB - We previously showed that Nuclear Factor κB (NF-κB) inactivation in astrocytes leads to improved functional recovery following spinal cord injury (SCI). This correlated with reduced expression of pro-inflammatory mediators and chondroitin sulfate proteoglycans, and increased white matter preservation. Hence we hypothesized that inactivation of astrocytic NF-κB would create a more permissive environment for axonal sprouting and regeneration. We induced both contusive and complete transection SCI in GFAP-Inhibitor of κB-dominant negative (GFAP-IκBα-dn) and wild-type (WT) mice and performed retrograde [fluorogold (FG)] and anterograde [biotinylated dextran amine (BDA)] tracing 8 weeks after injury. Following contusive SCI, more FG-labeled cells were found in motor cortex, reticular formation, and raphe nuclei of transgenic mice. Spared and sprouting BDA-positive corticospinal axons were found caudal to the lesion in GFAP-IκBα-dn mice. Higher numbers of FG-labeled neurons were detected immediately rostral to the lesion in GFAP-IκBα-dn mice, accompanied by increased expression of synaptic and axonal growth-associated molecules. After transection, however, no FG-labeled neurons or BDA-filled axons were found rostral and caudal to the lesion, respectively, in either genotype. These data demonstrated that inhibiting astroglial NF-κB resulted in a growth-supporting terrain promoting sparing and sprouting, rather than regeneration, of supraspinal and propriospinal circuitries essential for locomotion, hence contributing to the improved functional recovery observed after SCI in GFAP-IκBα-dn mice.
KW - Anterograde tracing
KW - Astrocytes
KW - GAP-43
KW - Neuroprotection
KW - Retrograde tracing
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=67649506550&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67649506550&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2009.06190.x
DO - 10.1111/j.1471-4159.2009.06190.x
M3 - Article
C2 - 19522780
AN - SCOPUS:67649506550
VL - 110
SP - 765
EP - 778
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 2
ER -