AIMS: 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. CONCLUSION: 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.
AIMS: 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. CONCLUSION: 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.
Authors: Alicia K Au; Yaming Chen; Lina Du; Craig M Smith; Mioara D Manole; Sirine A Baltagi; Charleen T Chu; Rajesh K Aneja; Hülya Bayır; Patrick M Kochanek; Robert S B Clark Journal: Biochim Biophys Acta Date: 2015-06-11