NZW rabbits were subjected to a 15 minute period of asphyxial CA followed by resuscitation and 120 minutes of reperfusion. Five groups of animals (n=4-6/group) were studied: Sham; Control (Ctrl); TH, CA with fast hypothermia induced by external cooling at reperfusion (target temperature: 32°C); NIM: IV bolus, at the onset of reflow, of 2.5 mg/kg NIM811 (a non immunosuppressive derivative of cyclosporine A); TH+NIM, hypothermia and NIM811-treated rabbits. The following measurements were carried out: pupillary response to light, cell damage marker (protein S100β), RISK pathway activation (P-Akt/Akt and P-ERK/ERK ratios) and on isolated mitochondria both calcium retention capacity (CRC, i.e. Ca2+ amount required for PTP opening) and respiration.
The characteristics of CA were similar among groups. Pupillary response to light, impaired after CA, was preserved by TH (p<0.05 vs. Ctrl). The increase in S100β protein was prevented by TH (p<0.05 vs. Ctrl). TH improved the CRC (altered, by CA) and the ADP – stimulated mitochondrial respiration (p<0.05 vs Ctrl). CA did not increase P-Akt/Akt whereas P-ERK/ERK was significantly increased in the control group (p<0.05 vs. SHAM). TH significantly enhanced P-Akt/Akt while preventing increase in P-ERK/ERK (p<0.05 vs Ctrl). Similar results were obtained in NIM and TH+NIM groups (p<0.05 vs Ctrl).
In our model, TH promoted activation of Akt and limited CAinduced brain damage by inhibiting PTP.
The author hereby declares no conflict of interest