Application Of MicroPET In Models Of Epilepsy And Cerebral Ischemia

Positron emission tomography(PET)is a noninvasive imaging technique thatallows quantitative in vivo determinations of the rates of various physiologic andbiochemical processes with minimal invasiveness.However,PET has not been suitablefor small animal models because of resolution limitations.Until recently,improvement in scanner resolution has allowed PET to become apotential method to monitor cerebral metabolic pattems in rat brain using small animalpositron emission tomography(MicroPET).Moreover,MicroPET can also be used inthe early stage of acute brain lesions,which cannot be accomplished in the clinical PETstudies because tracer kinetics is unwarranted and image acquisition is difficult in theearly phase of acute stage.The tracer 2-[18F]-fluoro-2-deoxy-D-glucose(¹⁸F-FDG)isthe well-known radiotracer that frequently has been used as a marker of metabolicactivity for glucose.The level of glucose metabolism correlates with the degree ofneuronal activity.Epilepsy and cerebral ischemia are common neurological diseaseswhich show significant change of brain glucose metabolism.Ourstudy is aim toevaluation of new treatments for epilepsy and cerebral ischemia using MicroPET.Although PET images are not always simple to interpret because of the pooranatomical detail that they contain,in this study,we have co-registered a single MRItemplate with PET images,which greatly improves the interpretation of the PET images. At the same time,we improve the method of anesthesia and ensure the MicroPETimages reflect glucose metabolism of the conscious state.Part 1:Anterior thalamic nucleus stimulation modulates regional cerebralmetabolism:an FDG-MicroPET study in ratsThe mechanism underlying the antiepileptic function of deep brain stimulation(DBS)of the anterior thalamic nucleus(ATN)remains unknown.Experimental studiesrevealed that DBS of the ATN has a similar anticonvulsant action with ATN lesions.We measured the regional normalized cerebral metabolic rate of glucose(nCMRglc)with MicroPET in animals receiving either ATN stimulation or lesioning.Bilateral ATNstimulation reversibly increased nCMRglc in the target region,the thalamus andhippocampus,and decreased nCMRglc in the cingulate cortex and frontal cortex(including motor cortex).However,bilateral ATN lesioning decreased nCMRglc onlyin the target region.Animals with bilateral ATN lesions showed no metabolic changesafter ATN stimulation.Thus,bilateral DBS of the ATN reversibly induces metabolicactivation of the target area and modulates energy metabolism in remote brain regionsvia efferent or afferent fibers in rats.DBS of the ATN may work by a differentmechanism than ATN lesioning.Part 2:A study on the mechanism of repetitive transcranial magnetic stimulationtreatment after cerebral ischemia in ratsThe effect of repetitive transcranial magnetic stimulation(rTMS)hasfrequency-dependent.It is generally assumed that higher frequencies(＞1 Hz)induce anincrease of cortical excitability.Therefore,rTMS may be useful tool to modulate brainactivity for enhance recovery in acute cerebral ischemia.We applied an intraluminalmiddle cerebral artery occlusion model in rats under controlled conditions.20Hz rTMSwere delivered 1 hour after ischemia and interval 24h for 7 days.The resultsdemonstrated that 20Hz rTMS therapy significantly improved the neurological deficitsand reduced infarct volume of brain.Moreover,glucose metabolism in the ischemic area underwent a severe decrease during 7 days after ischemia,while 20Hz rTMStreatment significantly attenuated the decrease in cerebral metabolic rate of glucose inthe ischemic hemisphere.The results of immunohistochemistry demonstrated that20Hz rTMS therapy inhibited neuronal apoptosis and increased the expression ofGLUT-1 and GLUT-3 in the infarct margin.Our results demonstrate that 20Hz rTMStherapy inhibited neuronal apoptosis and maintenance of glucose metabolism in theischemic hemisphere,which might contribute to the the understanding neuroprotectioneffects of 20Hz rTMS therapy on transient cerebral ischemia in rats.In conclusion,we showed that MicroPET is a useful and provide the possibility toperform serial follow-up studies to investigate the development of functional changes inthe rat brain over time,will become important tools for epilepsy and cerebral ischemiaresearch.More important,an advantage of MicroPET is that the same molecularradiotracers can be used for both animal research and clinical applications facilitating amore rapid progression from preclinical research to clinical practice.In the future,MicroPET may also play a role in the development and evaluation of new treatments forepilepsy and cerebral ischemia.