Introduction:
After transient global cerebral ischemia, selective vulnerable brain areas show delayed neuronal degeneration with characteristic signs of apoptosis. Recent data demonstrated potent neuroprotective effects of the application of granulocyte colony-stimulating factor (G-CSF) after focal cerebral ischemia. In order to assess possible effects of intracerebroventricular application of G-CSF on cerebral recovery after global cerebral ischemia due to cardiac arrest (CA) neurological testing according to a tape removal test as well as histological analysis of the hippocampal CA-1 sector were performed.
Methods:
Global cerebral ischemia was initiated by ventricular fibrillation in rats during general anesthesia. After 6 min of CA cardio pulmonary resuscitation (CPR) was initiated. After restoration of spontaneous circulation (ROSC) the animals were divided into two groups (G-CSF vs. placebo; n=16 per group). G-CSF (4μl=3.84μg) or placebo was applied in single shot technique 30 min after ROSC. During CA, CPR and for the first 24 h after ROSC all animals were kept normothermic using a feedback control system with intraperitoneal implanted telemetric probes. The tape removal test was applied pre-CA, 24 h, 3 d, 7 d, 10 d and 14 d after ROSC. After 14 days histological analysis was done by counting TUNEL positive neurons in the hippocampal CA-1 sector. All experiments were performed in a randomized and blinded setting.
Results:
All animals were kept normothermic within the first 24 h after ROSC (G-CSF: 37.3 ± 0.3 °C; placebo: 37.5 ± 0.5 °C). Pre-CA all animals removed the adhesive tapes promptly. After ROSC in both treatment groups a clear neurological damage was shown that improved within the first 14 days, without reaching baseline values. No statistically significant differences between the group could be seen. With regard to TUNEL-positive neurons in the hippocampal CA-1 sector no significant differences could be observed between the groups (G-CSF: 47 ± 22; placebo: 51 ± 24).
Conclusions:
Regarding neurological recovery and neurohistopathological outcome 14 d after global cerebral ischemia, the present study was not able to show any beneficial effects of G-CSF, despite the well known effects of G-CSF in non global cerebral ischemia models.
Neuroprotective Effect of Granulocyte Colony–Stimulating Factor After Focal Cerebral Ischemia