Abstract P27: Microglial Activity and Therapeutic Hypothermia Post Cardiac Arrest Resuscitation in Rats
Background Therapeutic hypothermia after cardiac arrest (CA) improves survival and functional outcomes, but its neuroprotective mechanism remains unclear. We previously showed that immediate initiation of hypothermia post-CA led to better neuro-electrical and behavioral recovery. In this study, we quantified the impact of immediate versus conventional hypothermia with stereological technique on microglia (using expression of ionized calcium binding adaptor molecule 1 - Iba1), astrocytes (using expression of glial fibrillary astrocyte protein - GFAP), and neurons (by Cresyl-violet staining with histopathological damage scoring - HDS).
Methods Forty-eight rats were randomly divided into 3 groups (n=16 per group), based on normothermia (NT, T=37°C), 6 hours of immediate hypothermia (IH, T=33°C, initiated immediately after CA), or 12 hours of conventional hypothermia (CH, T=33°C, initiated one hour after CA) after CA. Each group was then evenly divided to 2 subgroups (n=8 based on 7 or 9 min asphyxial time). Hypothermia was maintained using surface cooling. Neurological recovery was evaluated using serial Neurological Deficit Score (NDS) calculation.
Results Better recovery by NDS 72 hours post-CA was noted in rats treated with IH (median, interquartile range: 72, 63–74), compared to CH (66, 43–70), and NT (51, 0 – 65) (p=0.005). There was a significantly different proportion of ischemic neurons by HDS in cortex (IH: 18.9±2.5%, CH: 33.2±4.4%, NT: 36.2±4.7%, p=0.002) and CA1 (IH: 14.4±2.9%, CH: 24.6±5.4%, NT: 49.2±5.3%, p<0.001). There was significant less Iba-1 expression in CH compared to IH (p=0.042) and NT (p=0.012) in cortex and CA1. There was no difference for GFAP expression in cortex or CA1.
Conclusions Immediate hypothermia leads to better functional outcome and lower ischemic neuronal injury in rats after CA. Temperature manipulation seems to affect the immune response to CA, with increased microglial activity in the IH and NT groups compared to CH group in this injury model. The longer hypothermia duration may decrease the microglia activation in response of central nervous system to CA than short duration in this injury model. No difference was noted in the astrocytic activity in the different groups.