THE INFLUENCE OF ANESTHESIA IN THE CENTRAL NERVOUS SYSTEM STUDY

Central nervous system is a complex machine; it is constituted by more or less 172 billions of cells divided between neurons and glia. This incredible number of cells, particularly neurons, are constantly connected, working 24 hours a day, never stopping. Their activity is maintained even during particular conditions such as sleep, pathological unconsciousness (coma) or general anesthesia. For all these peculiarities, since ancient times, man has devoted much effort to the study of the most fascinating organ of living beings (mammals in particular). Nowadays, thanks to the advance in medical technology, many tools are available to “look inside the brain”. Magnetic resonance imaging and, particularly, functional magnetic resonance imaging (fMRI) is a modern biomedical imaging method, which allows a non-invasive assessment of brain function. The detection of brain activity is based on the coupling between neuronal activity, energy consumption, and blood flow. Functional connectivity (FC) of brain regions is modulated in various central nervous system diseases, during sleeping and general anesthesia. Anesthesia during MRI procedures is commonly used in preclinical setting and, sometimes, is required also in clinical setting (uncollaborative patients, children, drugs induced-coma etc). The study of the relationship between anesthetics and FC presents a double value: allows to distinguish the alterations induced by anesthesia on FC, avoiding possible confounding elements, and permits an in depth investigation of drugs behaviour. For all these reasons, the main topic of this PhD dissertation is the relationship between anesthesia and central nervous system. We started from theoretical studies in healthy subjects and we arrived to clinical setting, describing the possible application of anesthetics drugs as a treatment of neurologic diseases. The first study included aims to describe the way in which dexmedetomidine and isoflurane modulate FC in guinea pigs. We analysed the characteristic of cortical, subcortical and cortico- subcortical connectivity under both drugs with resting state fMRI. The second study presented partial results of a more complex work concerning FC in rats under 4 different anesthetics protocols. Because in FC studies blood flow represents a crucial element we dedicated a part of the work to the study of haemodynamic alterations through the administration 3 of contrast medium. Dynamic Suceptibility Contrast MRI analysis allows the study of cerebral blood flow and cerebral blood volume of different brain anatomic regions under dexmedetomidine, isoflurane, midazolam-dexmedetomidine and midazolam-isoflurane. Finally, we moved to clinical setting to describe the successful treatment of 3 dogs suffering from idiopathic epilepsy presented in emergency department in a state of super refractory status epilepticus. They were treated successfully with a continuous infusion of dexmedetomidine and ketamine. In conclusion, taken together this thesis gives a little contribute to better understand anesthetics behavior at brain level. We believe that it is important to make a “rational choice” when we decide the anesthetic protocol for neuroimaging procedures (both in clinical and preclinical setting) and this “rational choice” could be make only if we have a widespread literature that describe the highest number of anesthetic protocol and their interaction on central nervous system. Finally, thanks to the continuous improvement of our understanding of anesthetics mechanism of action, especially from a molecular and functional point of view, is it possible to use different anesthetics as a therapy for different neurologic conditions, particularly the one based on neurotransmitters imbalance.