Postischemic hypothermia

Welsh FA, Harris VA. Postischemic hypothermia fails to reduce ischemic injury in gerbil hippocampus. J Cereb Blood Flow Metab 1991 11 617-620. 

Huh P. W., Belayev L., Zhao W., Koch S., Busto R., and Ginsberg M. D. (2000) Comparative neuroprotective efficacy of prolonged moderate intraischemic and postischemic hypothermia in focal cerebral ischemia. J. Neurosurg. 92,91-99. 

Our group was able to show that 12.5 min of normothermic global ischemia led to significant, 7- to 12-fold increases in the striatal excitotoxic index that persisted for 3 4 h. By contrast, animals with postischemic hypothermia (30°C for 3 h) showed no changes in the excitotoxic index during recirculation (103). 

The preceding observations are obviously relevant to the neuro-protective effect of intraischemic hypothermia. Late increases in extracellular glutamate and aspartate levels have also been reported after ischemia (104) and following multiple ischemic insults (105). It is possible that prolonged postischemic hypothermia may affect these late processes, although this has not been established. 

Dietrich W. D., Lin B., Globus M. Y., Green E. J., Ginsberg M. D., and Busto R. (1995) Effect of delayed MK-801 (dizocilpine) treatment with or without immediate postischemic hypothermia on chronic neuronal survival after global forebrain ischemia in rats. J. Cerebr. Blood Flow Metab. 15, 960-968. 

Pazos A. J., Green E. J., Busto R., et al. (1999) Effects of combined postischemic hypothermia and delayed A-tert-butyl-alpha-pheylnitrone (PBN) administration on histopathological and behavioral deficits associated with transient global ischemia in rats. Brain Res. 846, 186-195. 

Dietrich W. D., Busto R., and Bethea J. R. (1999) Postischemic hypothermia and IL-10 treatment provide long-lasting neuroprotection of CA1 hippocampus following transient global ischemia in rats. Exp. Neurol. 158,444 -50. 

Colbourne F. and Corbett D. (1995) Delayed postischemic hypothermia a six month survival study using behavioral and histological assessments of neuroprotection. J. Neurosci. 15, 7250-7260. 

Colbourne F., Sutherland G., and Corbett D. (1997) Postischemic hypothermia. A critical appraisal with implications for clinical treatment. Mol. Neurobiol. 14, 171-201. 

Yanamoto H., Hong S. C., Soleau S., Kassell N. F., and Lee K. S. (1996) Mild postischemic hypothermia limits cerebral injury following transient focal ischemia in rat neocortex. Brain Res. 718, 207-211. 

Postischemic Hypothermia Provides Long-Term Neuroprotection in Rodents... 

Several studies using brief hypothermia have not found evidence of CA1 protection (18-22). However, such discordant findings are easily explained by a mismatch between the duration of hypothermia and the severity of the ischemic insult. For example, Chopp et al. (12) found that 2 h of postischemic hypothermia reduced CA1 loss against 8 but not 12 minofischemiainrats. Similarly, other experiments indicate thatthe duration of hypothermia is critical (14,17), as very brief cooling (e.g., 0.5 h) was ineffective while somewhat longer durations were (e.g., 5 h) protective, perhaps only transiently. 

A study by Dietrich et al. (23) found that 3 h of immediate postischemic hypothermia (30°C) reduced CA1 loss at short (i.e., 3 and 7 d) but not long survival times (2 mo) after 10 min 2-VO ischemia in rats. Because all of the aforementioned studies (e.g., refs. 10-14) used short survival times, it was argued that postischemic hypothermia was, by itself, of no long-term benefit. Other work has confirmed the ephemeral nature of CA1 protection afforded by brief hypothermia (24). Likewise, a slow maturation of CA1 neuronal loss occurs following short duration (e.g., 5 min) 4-VO (vertebral cauterization + bilateral carotid artery occlusion) ischemia (25). In the 4-VO model the a-amino-3-hydroxy-... 

We have investigated the ultrastructural morphology of ischemic CA1 cell death and the effects of delayed postischemic hypothermia... 

Although CA1 cell death was largely attenuated by postischemic hypothermia, some CA1 neurons nonetheless died, and the ultrastructural features of this death were typical of necrosis (e.g., membrane... 

In summary, the severity of ischemia has a critical impact on the amount of neuroprotection obtained with postischemic hypothermia (12,27). Brief hypothermic periods (e.g., <5 h) are not very efficacious and only delay cell death. Prolonged bouts (e.g., 24 -8 h) of hypothermia... 

STUDIES OF DELAYED POSTISCHEMIC HYPOTHERMIA IN CANINE GLOBAL CEREBRAL ISCHEMIA MODELS... 

The aforementioned findings in rodents mirror results observed in dogs subjected to cardiac arrest with subsequent postischemic mild hypothermia of 1- to 12-h duration (38-44). For example, a 12-h period of 34°C hypothermia with hemodilution and elevated blood pressure reduced brain injury (e.g., hippocampus, neocortex, basal ganglia) and lessened functional deficits after cardiac arrest. However, in all of these studies the survival time was 4 d or less, and thus it has yet to be proven that postischemic hypothermia can permanently reduce ischemic brain injury in the dog. Based on the rodent literature, it would be useful to investigate more protracted bouts of mild hypothermia and assess longterm outcome in this intensive cardiac arrest model in the dog. 

Coimbra C. G. and Cavalheiro E. A. (1990) Protective effect of short-term postischemic hypothermia on the gerbil brain. Braz. J. Med. Biol. Res. 23, 605-611. 

Iwai T., Niwa M., Yamada H., Nozaki M., and Tsurumi K. (1993) Hypothermic prevention of the hippocampal damage following ischemia in Mongolian gerbils comparison between intraischemic and brief postischemic hypothermia. Life Sci. 52,1031-1038. 

Coimbra C., Drake M., Boris-Moller F., and Wieloch T. (1996) Long-lasting neuroprotective effect of postischemic hypothermia and treatment with an anti-inflammatory/antipyretic drug. Evidence for chronic encephalopathic processes following ischemia. Stroke 27,1578-1585. 

Colboume F., Sutherland G., and Auer R. N. (1997) New features of delayed neuronal death in gerbils treated with prolonged postischemic hypothermia. Soc. Neurosci. Abstr. 23, 1917. 

De Bow S. B. and Colboume F. (2003) Delayed transient ischemic attacks kill some C A1 neurons previously salvaged with postischemic hypothermia neuroprotection undone. Brain Res. 959, 50-57. 

Corbett D., Hamilton M., and Colbourne F. (2000) Persistent neuroprotection with prolonged postischemic hypothermia in adult rats subjected to transient middle cerebral artery occlusion. Exp. Neurol. 163, 200-206. 

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