This study evaluated the effects of unilateral electroconvulsive therapy (UECT) on regional cerebral blood flow (rCBF) following experimentally induced stroke in rabbits. Five rabbits underwent right internal carotid artery ligation to induce stroke and were imaged with SPECT scans before and after being randomized to either receive UECT or act as controls. The three rabbits that received UECT showed improvement in rCBF in the affected region on the second SPECT scan, while the two control rabbits showed no improvement, indicating UECT may decrease infarct size following stroke. However, the study was limited by its small sample size.

1. Unilateral Electroconvulsive Therapy in Rabbit Stroke Model: Evaluation Using SPECT Deepak Agrawal, NK Gowda*, R Sagar**, PK Yadav***, Departments of Neurosurgery, Nuclear medicine*, Psychiatry** & Experimental Animal Facility*** All India Institute of Medical Sciences, New Delhi, India-110029

2. Background rCBF Increases following induced seizure Sestoft D, Meden P, Hemmingsen R, et al: Disparity in regional cerebral blood flow during electrically induced seizure. Acta Psychiatr Scand 1993;88:140-143.

3. Hypothesis This increase in rCBF may have a positive effect on the infarct size following stroke

4. AIMS & OBJECTIVES To evaluate the efficacy of unilateral electroconvulsive therapy (UECT) for cerebral protection following induced stroke in rabbits

5. Why Rabbit Model Vascular supply & distribution mimics human brain Induced strokes are more representative of humans

6. Why UECT? ECT has been previously shown to improve rCBF UECT causes marked improvement in CBF in the ipsilateral hemisphere B/L ECT improves perfusion in striatum Devanand DP, Dwork AJ, Hutchinson ER, Bolwig TG, Sackeim HA: Does ECT alter brain structure? Am J Psychiatry 1994;151:957-970 .

7. Materials & Methods Prospective randomized controlled study Randomization: computer generated random number method Approval was taken from the institutional ethics committee for animal experiments.

8. Materials & Methods RABBITS New Zealand strain Weight- 2-3 kg Both Male and female animals were used

9. Materials & Methods Anesthesia Pre-anesthetized by 10% ketamine (20 mg/kg) given IM Continuous infusion of midazolam 0.2mg/kg and ketamine (0.2 ml/ kg/hour). 2ml of 0.5% lignocaine was infiltrated S/C

10. Materials & methods Operative Procedure Femoral cut down for IV access 2cm long incision along ant border of SCM Using blunt dissection CCA exposed ICA identified & ligated with silk. Wound closed

11. Materials & Methods 2 mCi of Tc-99m HMPAO (Amersham, England) was then injected into the femoral vein, 10 minutes after induced stroke (carotid ligature).

12. Materials & Methods Animal transported to nuclear medicine on a modified trolley, on ventimask and IV. Planar and SPECT images of the brain were taken 50 minutes after stroke.

13. Materials & Methods UECT Group rabbits Unilateral Rt ECT was given 75 minutes after the induced stroke.

14. Materials & Methods ECT Procedure Modified Thymatron (TM) DGx, (Somatics LLC, Lake Bluff, IL, USA) ECT machine A brief-pulse square wave (0.5ms) & constant current of 0.9 A. Stimulus kept at 10% with impedence (resistance) of 800 ohms Induced seizure was considered adequate when its duration > 20 sec.

15. Materials & Methods CONTROL RABBITS NO UECT

16. Materials & Methods Both groups received 6 mCi of Tc-99m HMPAO after 90 minutes of stroke. A second set of planar and SPECT images were taken 150 minutes after stroke.

17. Materials & Methods Relative uptake of the radiotracer in both groups of rabbits was displayed on computer monitor and was analyzed using a graded grey scale. Cerebellum was used as reference site (100% maximum value) for all comparisons

18. Materials & Methods Rabbits sacrificed using high dose of pancuronium and thiopentone given IV.

19. STUDY DESIGN 5 RABBITS Rt ICA LIGATION SPECT Brain (50 min after stoke) Randomised to UECT Gp (n=3) Randomised to Control Gp (n=2) Rt Sided UECT No ECT REPEAT SPECT (120 min after stroke) ANIMAL SACRIFIED

20. RESULTS Study terminated prematurely as Ethics committee withdrew approval after 5 rabbits. UECT Group – 3 Rabbits Control Group- 2 Rabbits

21. RESULTS The right cerebrum showed decrease uptake of radiotracer compared to left cerebrum in all five rabbits confirming induction of ischemia.

22. RESULTS UECT Group There was improvement in the regional cerebral blood flow on the affected side in all three rabbits

23. UECT GROUP PRE-UECT POST-UECT

24. RESULTS Control group No control group rabbit showed any improvement in cerebral perfusion on delayed SPECT.

25. LIMITATIONS No of rabbits studied was small Embolic stroke model would have been preferred to carotid ligation PET would have been better in imaging the induced stroke

26. CONCLUSIONS All rabbits receiving UECT had improvement in cerebral perfusion following induced stroke, vis-à-vis the control group.

27. CONCLUSIONS This study shows that UECT decreases the infarct size and increases rCBF in rabbit stroke model. Further studies using a larger sample size will be required for confirmation.

28. Thank You