unilateral electroconvulsive therapy_in_rabbit_stroke_model1

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

UECT in rabbit stroke model

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.


Hypothesis

• This increase in rCBF may have a positive effect on the infarct size following stroke


AIMS & OBJECTIVES

• To evaluate the efficacy of unilateral electroconvulsive therapy (UECT) for cerebral protection following induced stroke in rabbits


Why Rabbit Model

• Vascular supply & distribution mimics human brain

• Induced strokes are more representative of humans


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.


Materials & Methods

• Prospective randomized controlled study

• Randomization: computer generated random number method

• Approval was taken from the institutional ethics committee for animal experiments.


Materials & Methods

RABBITS• New Zealand strain• Weight- 2-3 kg• Both Male and female animals were used


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


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


Materials & Methods

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


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.


Materials & Methods

UECT Group rabbits• Unilateral Rt ECT was given 75 minutes

after the induced stroke.


Materials & MethodsECT 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.


Materials & Methods

CONTROL RABBITS

• NO UECT


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.


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


Materials & Methods

Rabbits sacrificed using high dose of pancuronium and thiopentone given IV.


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


RESULTS

• Study terminated prematurely as Ethics committee withdrew approval after 5 rabbits.

• UECT Group – 3 Rabbits• Control Group- 2 Rabbits


RESULTS

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


RESULTS

UECT Group

• There was improvement in the regional cerebral blood flow on the affected side in all three rabbits


UECT GROUP

PRE-UECT POST-UECT


RESULTS

Control group

• No control group rabbit showed any improvement in cerebral perfusion on delayed SPECT.


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


CONCLUSIONS

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


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.


Thank You

unilateral electroconvulsive therapy_in_rabbit_stroke_model1

Health & Medicine

induced stroke

minutes of stroke

groups of rabbits

rabbit stroke model

rcbf uect

stroke carotid ligature

infarct size following

induced seizure sestoft