Abstract
Mechanical trauma to the spinal cord triggers events resulting in the death of neurons and glia over several weeks following the initial injury. It has been suggested that the prevention of delayed apoptosis after spinal cord injury (SCI) is likely to have a beneficial effect by reducing the extent of neuronal and oligodendroglial death, which would translate into better functional outcomes. Drugs acting at different levels in the apoptotic cascade (i.e., caspase inhibitors and antiapoptotic Bcl-xL) have been shown to decrease apoptotic cell death, but benefits in functional outcomes result only when inflammation is also decreased. Furthermore, long-term antiapoptotic therapy can result in nonapoptotic death with necrotic features, which will further increase inflammation and worsen outcome. Even though neuroprotective therapies are one of the targets for the promotion of functional recovery after SCI, targeting only post-SCI apoptosis is unlikely to be as successful as more integrated interventions that also target inflammation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 425-434 |
| Number of pages | 10 |
| Journal | Future Neurology |
| Volume | 2 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jul 2007 |
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Keywords
- Apoptosis
- Bcl-2 family
- Bcl-xL
- Caspases
- Functional recovery
- Inflammation
- Necrosis
- Neuronal cell death
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
Cite this
Antiapoptotic therapies in the treatment of spinal cord injury. / Cittelly, Diana M.; Perez-Polo, J. Regino.
In: Future Neurology, Vol. 2, No. 4, 07.2007, p. 425-434.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antiapoptotic therapies in the treatment of spinal cord injury
AU - Cittelly, Diana M.
AU - Perez-Polo, J. Regino
PY - 2007/7
Y1 - 2007/7
N2 - Mechanical trauma to the spinal cord triggers events resulting in the death of neurons and glia over several weeks following the initial injury. It has been suggested that the prevention of delayed apoptosis after spinal cord injury (SCI) is likely to have a beneficial effect by reducing the extent of neuronal and oligodendroglial death, which would translate into better functional outcomes. Drugs acting at different levels in the apoptotic cascade (i.e., caspase inhibitors and antiapoptotic Bcl-xL) have been shown to decrease apoptotic cell death, but benefits in functional outcomes result only when inflammation is also decreased. Furthermore, long-term antiapoptotic therapy can result in nonapoptotic death with necrotic features, which will further increase inflammation and worsen outcome. Even though neuroprotective therapies are one of the targets for the promotion of functional recovery after SCI, targeting only post-SCI apoptosis is unlikely to be as successful as more integrated interventions that also target inflammation.
AB - Mechanical trauma to the spinal cord triggers events resulting in the death of neurons and glia over several weeks following the initial injury. It has been suggested that the prevention of delayed apoptosis after spinal cord injury (SCI) is likely to have a beneficial effect by reducing the extent of neuronal and oligodendroglial death, which would translate into better functional outcomes. Drugs acting at different levels in the apoptotic cascade (i.e., caspase inhibitors and antiapoptotic Bcl-xL) have been shown to decrease apoptotic cell death, but benefits in functional outcomes result only when inflammation is also decreased. Furthermore, long-term antiapoptotic therapy can result in nonapoptotic death with necrotic features, which will further increase inflammation and worsen outcome. Even though neuroprotective therapies are one of the targets for the promotion of functional recovery after SCI, targeting only post-SCI apoptosis is unlikely to be as successful as more integrated interventions that also target inflammation.
KW - Apoptosis
KW - Bcl-2 family
KW - Bcl-xL
KW - Caspases
KW - Functional recovery
KW - Inflammation
KW - Necrosis
KW - Neuronal cell death
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UR - http://www.scopus.com/inward/citedby.url?scp=34447302064&partnerID=8YFLogxK
U2 - 10.2217/14796708.2.4.425
DO - 10.2217/14796708.2.4.425
M3 - Article
AN - SCOPUS:34447302064
VL - 2
SP - 425
EP - 434
JO - Future Neurology
JF - Future Neurology
SN - 1479-6708
IS - 4
ER -