Introducing a Developed Model of Reversible Cardiac Arrest to Produce Global Brain Ischemia and Its Impact on Microtubule-Associated Protein Tau Phosphorylation at Ser

Shohreh Majd, John H T Power, Simon Koblar, Hugh J M Grantham

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Brain ischemia is a consequence of stroke and cardiac arrest (CA), leading to short and long-term neurological impact involving cognitive function as well as dementia. An accurate, simple and reproducible model of CA ischemia and reperfusion is valuable in assessing the response to ischemia and therapeutic interventions. In the current study the effectiveness of a reversible
model of CA has been assessed through examining the brain response in expressing tau and hyperphosphorylated tau (p-tau) protein, one of the main hallmarks of Alzheimer’s disease.
Method: In the current study we used a two phase alternating current (AC)-derived reversible CA to generate global-brain ischemia through ventricular fibrillation (VF)/ventricular standstill followed by defibrillation, mechanical ventilation and standard resuscitation in 26 female adult Sprague Dawley rats. This model mimics CA in humans and allows testing of experimental interventions to restore/ preserve brain function. Two phases of AC (24 Volts (V) followed by 18 V) were applied through a two-ring oesophageal wire. After 2-, 4- and 8-minute CA, resuscitation was initiated by ventilation, 8 Joules (J) chest electrical shock in the event of VF, adrenaline injection and manual chest compression. ECG, pulse rate and blood oxygen saturation were recorded during the resuscitation. Tau and p-tau levels were assessed as an indicator of neuronal
response to ischemia.
Results: Resuscitation outcomes were assessed at 1st and 2nd hour and 4th week of restoration of blood circulation and animal survival. We report an early tau dephosphorylation which was followed by hyperphosphorylation after 4 weeks, while the total tau remained unchanged.
Conclusions: This method successfully produced reproducible global brain ischemia generating tau dephosphorylation in shortterm recovery and hyperphosphorylation in long-term recovery. The findings show the efficiency of this technique in providing a tool to study the further neuronal response to ischemic situations and the underlying mechanisms.
Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalInternational Journal of Neurology and Neurotherapy
Volume3
Issue number1
Publication statusPublished - 2016

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