=Acta-v-7-. - . Ndurochlrurglca

Acta Neurochir (Wien) (1992): 114:51-58

9 Springer-Verlag 1992 Printed in Austria

A Modified Model of Reversible Middle Cerebral Artery Embolization in Rats Without Craniectolny* L. Csiba 1, D. Bereczki 2, T. Shima, Y. Okada, K. Yamane, T. Yamada, M. Nishida, and Sh. Okita 1 Department of Neurology and Psychiatry, University Medical School Debrecen, Hungary and Chugoku Rousai Hospital, Kure City, Japan

Summary A detailed description is given of a new model of reversible focal cerebral ischaemia in rats. A spherical embolus, attached to the end of an 8-0 surgical thread was injected into the middle cerebral artery (MCA) via the external and internal carotid arteries (ECA and ICA) and could be withdrawn by pulling the extravascular portion of the thread when reperfusion was to follow ischaemia. In contrast to similar techniques, the 8-0 thread did not block blood flow in either the common carotid artery (CCA) or the ICA during ischaemia and, as the CCA did not have to be ligated, flow could be restored via the ipsilateralCCA and ICA after the ischaemic period. Neurological deficit, mortality rate, tissue water content, regional pH, ATP and, in some experiments, electroencephalogram (EEG) and cerebral blood flow (CBF) were evaluated in ischaemia and after various length of reperfusion. The overall mortality rate was 21%; all these animals were lost in the first hours of recirculation. The water content of their brains differed significantly from those who survived 24 hours (81 and 77 % respectively). A significant difference in CBF of the ipsi- and contralateral putamen was found immediately after embolization (a CBF decrease of 26 • 5 and 5 • 5 ml/100 g/rain, respectively), and relative hyperperfusion (+ 23 + 27 ml/100 g/min) was observed in the ipsilateral putamen during reperfusion. EEG amplitude declined on both the affected and non-affected sides after embolization (to 54• 8% and 71 :k 6% of pre-ischaemic values) and remained decreased (66 • 8% of control) on the ipsilateral side after 1 hour of reperfusion. Embolization resulted in tissue acidosis and ATP depletion predominantly in the somatosensory cortex, caudoto-putamen, internal capsule, anterior thalamus and hippocampus. The spatial extent of metabolic alterations increased in the first two hours of recirculation, then decreased by 24 hours, together with the improvement of clinical signs. Providing a better model for human embolic strokes this model is suggested for studying consequences of reversible focal ischaemia.

Keywords: Animal models; cerebral ischaemia; cerebral blood flow; brain pH; embolization; reperfusion; rats. Introduction M o d e l s o f p e r m a n e n t focal i s c h a e m i a m o d e l s ind u c e d b y the occlusion o f an i n t r a c r a n i a l artery, -

u s u a l l y the p r o x i m a l m i d d l e c e r e b r a l a r t e r y ( M C A ) have been widely used in v a r i o u s a n i m a l s such as r a b b i t s 1, cats 2, dogs 3, 4 a n d rats 5. Reversible focal ischaemic m o d e l - r e s t o r a t i o n o f b l o o d flow i n d u c e d b y the release o f the t e m p o r a r y clip on the m i d d l e c e r e b r a l a r t e r y - in m o n k e y s , cats a n d rats has b e c o m e also possible 5' 6, 7 H o w e v e r , m e t h o d s e x p o s i n g a n d directly clipping the M C A have some d i s a d v a n t a g e s : they require c r a n i o t o m y with the risk o f a p o t e n t i a l C S F fistula, they m i g h t injure nerve fibers in the a d v e n t i t i a o f the M C A , a n d the excessive m a n i p u l a t i o n o f the vessel d u r i n g surgical e x p o s u r e a n d the resulting v a s o s p a s m m i g h t alter p o s t - i s c h a e m i c a n d / o r c o l l a t e r a l b l o o d supply. So, new m e t h o d s were n e e d e d for reversible M C A occlusion, w i t h o u t c r a n i e c t o m y . N e w m o d e l s o f reversible M C A occlusion were dev e l o p e d in rats recently, using a h a r d e n e d , r a t h e r thick silicon-coated i n t r a l u m i n a r n y l o n thread, which was a d v a n c e d t h r o u g h the internal c a r o t i d artery ( I C A ) to occlude the origin o f the M C A 8' 9, 10. T h e m e t h o d o f a d v a n c i n g a h a r d e n e d , relatively l o n g a n d thick emb o l u s has, however, some d i s a d v a n t a g e s : A. It does n o t result in the occlusion o f a single vessel ( M C A ) d u r i n g the ischaemic p e r i o d , b u t c o m p l e t e l y b l o c k s the b l o o d flow in the I C A , external c a r o t i d a r t e r y ( E C A ) a n d M C A d u r i n g the ischaemic p e r i o d , which does n o t usually h a p p e n in h u m a n e m b o l i c strokes where a single e m b o l u s blocks only a single a r t e r y leaving the flow u n d i s t u r b e d in the I C A a n d o t h e r vessels. B. T h e loc a t i o n where the e m b o l u s lodges in e m b o l i c strokes d e p e n d s on the size o f the e m b o l u s a n d on haemo-. d y n a m i c factors, while the length o f the t h r e a d a n d the force b y which it is inserted is the critical factor in the m e t h o d s m e n t i o n e d above. C. In the m o d e l o f N a g a -

* Presented in part at the International Conference on Stroke, Geneva, Switzerland, May 30-June 1, 1991,

L. Csiba etal.: Reversible MCA Embolization Model in Rats

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sawa and Kogure 1~ the ischaemic area can be reperfused only through the circle of Willis as the ipsilateral CCA and ECA had been ligated, i.e. the normal flow from the CCA into the ICA is not restored during reperfusion. To avoid these problems we elaborated an embolization technique in rats, which occludes only a single vessel (MCA), leaving flow in the internal, anterior and posterior cerebral arteries undisturbed during the ischaemic period and where the lodging of the embolus depends on haemodynamic factors. This method is an adaptation of the reversible MCA embolization technique of Molnfir e t a l ] 1 modified to be applicable for rats.

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