In anesthetized adult cats, acute stroke was produced by transorbital occlusion of the left middle cerebral artery. A battery of imaging techniques was used for simultaneous evaluation of regional blood flow, glucose utilization, protein synthesis, pH, and the regional tissue content of glucose, ATP, and potassium. The electrophysiological impact of stroke was monitored by EEG frequency analysis and recording of somatosensory evoked potentials. Two hours after vascular occlusion, a close correlation existed between the degree of electrophysiological changes and biochemical alterations, in particular with the extent of tissue acidosis, ATP depletion, decrease of tissue potassium content, and suppression of protein synthesis. However, there was only a poor correlation with blood flow and glucose utilization. Both of these exhibited a greatly inhomogeneous pattern with regions of reduced, normal, or increased rates. In areas remote from the infarct, the content of biochemical substrates was normal but blood flow was reduced globally by ∼50% and glucose utilization by ∼20%. An anatomically defined regional pattern of cerebral or cerebellar diaschisis was not observed. It is concluded that during the acute phase of stroke, imaging of blood flow and glucose utilization does not provide an accurate estimate of the actual functional or metabolic disturbance. For the clinical evaluation of the development or treatment of stroke, in consequence, alternative noninvasive techniques such as imaging of protein synthesis and/or pH may be more relevant.
Cerebral blood flow, studied by means of a diffusible indicator, remains unchanged in the aging process (developmental changes). On the contrary, brain activity, evaluated by deoxyglucose uptake, is significantly reduced. Papaverine, which increases cerebral blood flow, and vincamine, slightly but significantly, act on this parameter in the older animals.
up i n t h e b r a i n ( 1 ) . Among t h e s u b s t a n c e s s t u d i e disopropyl-p-iodo-amphetamine was s e l e c t e d t o measure r e g i o n a l c e r e b r a l blood flow i n man (2,3). p-iodo-amphetamine, a m e t a b o l i t e o f isopropyl-p-iodo-amphetamine i s a l s o t a k e n up i n t h e b r a i n with a high index ( 4 ) . I t was n e c e s s a r y t o s y n t h e s i z e t h i s new tracer w i t h a high s p e c i f i c a c t i v i t y i n o r d e r t o t e s t i t s p r o p e r t i e s .The s p e c i f i c a c t i v i t y a f t e r t h e exchange r e a c t i o n between p-iodo-amphetamine and r a d i o a c t i v e i o d i n e i s always low and t h e r e f o r e we p r e f e r e d t o s y n t h e s i z e t h i s molecule d i r e c t l y u s i n g t h e Sandmeyer r e a c t i o n from r a d i o a c t i v e i o d i n e and p-aminoamphetamine (Scheme 1).
Transient ischemia results in changes in the cerebral blood flow at the level of microinfarcts, enzymatic and metabolic changes and the development of a cerebral edema; all these disorders regress in the week following ischemia. Besides, the observed functional disorders disappear as the cerebral edema regresses. The brain functional activity is protected by the use of treatments which reduce the development of the cerebral edema and/or a quicker regression of the edema.
Rats were injected with iodoamphetamine synthesized and labeled with 125I or with 125I- isopropyliodoamphetamine , a molecule of established value for the determination of local cerebral blood flow. The blood kinetics, tissue distribution, and brain uptake index for each tracer exhibited practically no differences. Autoradiographic quantification of the local cerebral blood flow, calculated according to the microsphere model, produced identical results for both molecules. However, compared with the values reported for other tracers, our values constituted an underestimation of white matter blood flow and a more real estimation of hippocampal flow. It is concluded from the brain uptake of the derivatives of both amphetamines during the first minutes following their injection that these tracers can be used as a chemical microembolus for the measurement of local cerebral blood flow.
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