Cerebellar Purkinje cell neurodegeneration after cardiac arrest: effect of therapeutic hypothermia.
OBJECTIVE
The cerebellum is among the brain regions most vulnerable to damage caused by cardiac arrest, and cerebellar Purkinje cell loss may contribute to neurologic dysfunction, including post-hypoxic myoclonus. However, it remains unknown whether cerebellar Purkinje cells are protected by post-cardiac arrest therapeutic hypothermia (TH). Therefore, we examined the effect of post-cardiac arrest TH onset and duration on cerebellar Purkinje cell loss.


METHODS
Samples from a previously published study of post-cardiac arrest TH were utilized for the present analysis. Adult male rats subjected to asphyxial cardiac arrest and cardiopulmonary resuscitation were block randomized to normothermia (37.0°C) or TH (33.0°C) initiated 0, 1, 4, or 8h after return of spontaneous circulation (ROSC) and maintained for 24 or 48 h. Cerebella from rats surviving 7 days after ROSC were processed for histology and immunohistochemistry. Purkinje cell density was quantified in Nissl-stained sections of the primary fissure of the cerebellar vermis.


RESULTS
With post-cardiac arrest normothermia, Purkinje cell density in the primary fissure was severely reduced compared to sham-injured controls (3.8 ± 1.8 cells mm(-1) vs. 35.9 ± 2.4 cells mm(-1), p<0.001). TH moderately improved Purkinje cell survival in all groups combined (14.0 ± 5.6 cells mm(-1), p<0.001 compared to normothermia). There was no statistical difference in Purkinje cell protection based on TH onset time or duration.


CONCLUSIONS
These results indicate that post-cardiac arrest TH protects selectively vulnerable cerebellar Purkinje cells within a broad therapeutic window. The potential clinical implications for improving Purkinje cell survival require further investigation.
Center for Resuscitation Science, Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, United States.
Michael Gregory
MG
Paine
Dongfang
D
Che
Luchuan
L
Li
Robert William
RW
Neumar
D000818:Animals; D002531:Cerebellum / Q000473:pathology*; D006323:Heart Arrest / Q000473:pathology* / Q000628:therapy*; D007036:Hypothermia, Induced; D008297:Male; D011689:Purkinje Cells / Q000473:pathology*; D051381:Rats