https://www.cambridge.org/core/journals/canadian-journal-of-neurological-sciences/article/effect-of-combination-therapy-with-neuroprotective-and-vasoprotective-agents-on-cerebral-ischemia/A0C31F17ACF68D3D3DA9AFF33853ACAE
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- https://doi.org/10.1017/cjn.2018.8
- Published online: 14 May 2018
Abstract
Because most tested drugs are active against only one of the damaging processes
associated with stroke, other mechanisms may cause cellular death. Thus, a combination of
protective agents targeting different pathophysiological mechanisms may obtain better
effects than a single agent. The major objective of this study was to investigate the
effect of combination therapy with vascular endothelial growth factor (VEGF) and nerve
growth factor (NGF) after controlled ischemic brain injury in rabbits.
Methods: Animals were randomly assigned to one of the
following groups: sham group, saline-treated control group or NGF+VEGF-treated group.
Animals received an intracerebral microinjection of VEGF and NGF or saline at 5 or 8 hours
after ischemia. The two specified time points of administration were greater than or equal
to the existing therapeutic time window for monoterapy with VEGF or NGF alone (3 or 5
hours of ischemia). Infarct volume, water content, neurological deficits, neural cell
apoptosis and the expression of caspase-3 and Bcl-2 were measured.
Results: Compared with saline-treated controls, the
combination therapy of VEGF and NGF significantly reduced infarct volume, water content,
neural cell apoptosis and the expression of caspase-3, up-regulated the expression of
Bcl-2 and improved functional recovery (both p<0.01) when administered
5 or 8 hours after ischemia. The earlier the administration the better the
neuroprotection. Conclusions: These results showed that the
combination therapy with VEGF and NGF provided neuroprotective effects. In addition, the
time window of combination treatment should be at least 8 hours after ischemia, which was
wider than monotherapy.
Copyright
COPYRIGHT: © The Canadian Journal of Neurological Sciences Inc.
2018
Corresponding author
Correspondence to: Jiping Yang, Department of Medical Imaging, The Second
Hospital of Hebei Medical University, 215 West Heping Road, Shijiazhuang, 050000, Hebei
Province, China. Email: ran0511@sina.com
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