TY - JOUR
T1 - Cyclosporine A for neuroprotection
T2 - Establishing dosing guidelines for safe and effective use
AU - Cook, Aaron M.
AU - Whitlow, Justin
AU - Hatton, Jimmi
AU - Young, Byron
PY - 2009/7
Y1 - 2009/7
N2 - Numerous neuroprotective compounds have been investigated to ameliorate secondary changes and the progression of injury after the primary insult in traumatic brain injury (TBI). This cascade of events is complex and difficult to abate once initiated following the primary injury. The clinical consequences of this secondary injury are unpredictable and often permanently incapacitating. Cyclosporine A (CsA) interrupts the endogenous mediators of secondary insult through inhibition of the mitochondrial permeability transition pore and prevention of subsequent mitochondrial dysfunction. This drug may have a role in neuroprotection but has several pharmacologic effects that must be considered when using it in the TBI population. This review discusses the physiologic responses following TBI that may affect CsA efficacy and safety when used for neuroprotective indications. So far, CsA seems to be safe in the TBI population. The role of CsA after acute TBI will be better defined after the completion of upcoming planned clinical trials.
AB - Numerous neuroprotective compounds have been investigated to ameliorate secondary changes and the progression of injury after the primary insult in traumatic brain injury (TBI). This cascade of events is complex and difficult to abate once initiated following the primary injury. The clinical consequences of this secondary injury are unpredictable and often permanently incapacitating. Cyclosporine A (CsA) interrupts the endogenous mediators of secondary insult through inhibition of the mitochondrial permeability transition pore and prevention of subsequent mitochondrial dysfunction. This drug may have a role in neuroprotection but has several pharmacologic effects that must be considered when using it in the TBI population. This review discusses the physiologic responses following TBI that may affect CsA efficacy and safety when used for neuroprotective indications. So far, CsA seems to be safe in the TBI population. The role of CsA after acute TBI will be better defined after the completion of upcoming planned clinical trials.
KW - Cyclophilin D
KW - Mitochondrial permeability transition pore
KW - Secondary injury
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=67650523308&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67650523308&partnerID=8YFLogxK
U2 - 10.1517/14740330903066742
DO - 10.1517/14740330903066742
M3 - Review article
C2 - 19548859
AN - SCOPUS:67650523308
SN - 1474-0338
VL - 8
SP - 411
EP - 419
JO - Expert Opinion on Drug Safety
JF - Expert Opinion on Drug Safety
IS - 4
ER -