Adenosine treatment delays postischemic hippocampal CA1 loss after cardiac arrest and resuscitation in rats

Kui Xu, Michelle Puchowicz, W. David Lust, Joseph C. LaManna

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Resuscitation from cardiac arrest results in reperfusion injury that leads to increased postresuscitation mortality and delayed neuronal death. One of the many consequences of resuscitation from cardiac arrest is a derangement of energy metabolism and the loss of adenylates, impairing the tissue's ability to regain proper energy balance. In this study, we investigated the effects of adenosine (ADO) on the recovery of the brain from 12 min of ischemia using a rat model of cardiac arrest and resuscitation. Compared to the untreated group, treatment with adenosine (7.2 mg/kg) initiated immediately after resuscitation increased the proportion of rats surviving to 4 days and significantly delayed hippocampal CA1 neuronal loss. Brain blood flow was increased significantly in the adenosine-treated rats 1 h after cardiac arrest and resuscitation. Adenosine-treated rats exhibited less edema in cortex, brainstem and hippocampus during the first 48 h of recovery. Adenosine treatment significantly lowered brain temperature during recovery, and a part of the neuroprotective effects of adenosine treatment could be ascribed to adenosine-induced hypothermia. With this dose, adenosine may have a delayed transient effect on the restoration of the adenylate pool (AXP = ATP + ADP + AMP) 24 h after cardiac arrest and resuscitation. Our findings suggested that improved postischemic brain blood flow and ADO-induced hypothermia, rather than adenylate supplementation, may be the two major contributors to the neuroprotective effects of adenosine following cardiac arrest and resuscitation. Although adenosine did not prevent eventual CA1 neuronal loss in the long term, it did delay neuronal loss and promoted long-term survival. Thus, adenosine or specific agonists of adenosine receptors should be evaluated as adjuncts to broaden the window of opportunity in the treatment of the reperfusion injury following cardiac arrest and resuscitation.

Original languageEnglish (US)
Pages (from-to)208-217
Number of pages10
JournalBrain Research
Volume1071
Issue number1
DOIs
StatePublished - Feb 3 2006

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Heart Arrest
Resuscitation
Adenosine
Therapeutics
Induced Hypothermia
Brain
Neuroprotective Agents
Reperfusion Injury
Purinergic P1 Receptor Agonists
Adenosine Monophosphate
Adenosine Diphosphate
Energy Metabolism
Brain Stem
Hippocampus
Edema
Ischemia
Adenosine Triphosphate

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Adenosine treatment delays postischemic hippocampal CA1 loss after cardiac arrest and resuscitation in rats. / Xu, Kui; Puchowicz, Michelle; Lust, W. David; LaManna, Joseph C.

In: Brain Research, Vol. 1071, No. 1, 03.02.2006, p. 208-217.

Research output: Contribution to journalArticle

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