Lucia Merlo

THE ANATOMIC LOCATION OF THE SOUL FROM THE HEART, THROUGH THE BRAIN, TO THE WHOLE BODY, AND BEYOND: A JOURNEY THROUGH WESTERN HISTORY, SCIENCE, AND PHILOSOPHY

OBJECTIVETo describe representative Western philosophical, theological, and scientific ideas regarding the nature and location of the soul from the Egyptians to the contemporary period; and to determine the principal themes that have structured the history of the development of the concept of the soul and the implications of the concept of the soul for medical theory and practice. METHODSWe surveyed the ancient Egyptian, Greek, and Roman periods, the early, Medieval, and late Christian eras, as well as the Renaissance, Enlightenment, and Modern periods to determine the most salient ideas regarding the nature and location of the soul. RESULTSIn the history of Western theological, philosophical, and scientific/medical thought, there exist 2 dominant and, in many respects, incompatible concepts of the soul: one that understands the soul to be spiritual and immortal, and another that understands the soul to be material and mortal. In both cases, the soul has been described as being located in a specific organ or anatomic structure or as pan-corporeal, pervading the entire body, and, in some instances, trans-human and even pan-cosmological. Moreover, efforts to discern the nature and location of the soul have, throughout Western history, stimulated physiological exploration as well as theoretical understanding of human anatomy. The search for the soul has, in other words, led to a deepening of our scientific knowledge regarding the physiological and, in particular, cardiovascular and neurological nature of human beings. In addition, in virtually every period, the concept of the soul has shaped how societies thought about, evaluated, and understood the moral legitimacy of scientific and medical procedures: from performing abortions and autopsies to engaging in stem cell research and genetic engineering. CONCLUSIONOur work enriches our shared understanding of the soul by describing some of the key formulations regarding the nature and location of the soul by philosophers, theologians, and physicians. In doing so, we are better able to appreciate the significant role that the concept of the soul has played in the development of Western scientific, medical, and spiritual life. Although ideas about the soul have changed significantly throughout Western history, the idea of the soul as being real and essential to ones personhood has been, and remains, pervasive throughout every period of Western history.

Graphene in neurosurgery: the beginning of a new era.

Nanotechnology has revolutionized the approach to different fields of industry and medicine. Among the new nanomaterial used, one of the most promising appears to be graphene. Its versatility, due to a particular chemical configuration, confers to it enormous potential of application. Graphene has recently been tested also in biomedical research with excellent results. Neurosurgery can benefit of this material for therapeutic purposes such as targeting controlled drug/gene delivery in brain tumor treatment, as well as photothermal and photodynamic cancer therapy, improving biosensing and bioimaging, and lastly as biocompatible material for intracranial and/or spinal devices. However, it still remains an experimental material whose in vitro and in vivo toxicity is tested with controversial results for the human health. Noteworthy is the fact that it is not possible so far to know its long-term toxicity.

Simvastatin Administration Ameliorates Neurobehavioral Consequences of Subarachnoid Hemorrhage in the Rat

In the present study we assessed the neuroprotective effects of simvastatin in a rodent model of experimental subarachnoid hemorrhage (SAH). Based on recent data showing the role of statins not only in lowering the level of cholesterol but also in preventing cardiac and cerebrovascular damage in risk population, and in decreasing vasospasm and delayed ischemia after aneurysmal SAH, we investigated the neuroprotective effects of intraperitoneal administration of simvastatin (40 mg/kg/day for 5 consecutive days) in Sprague-Dawley rats 30 min after SAH, as compared to vehicle-treated SAH animals. We employed a battery of well-characterized tests to assess memory, learning, motivational, balance, and behavioral performances. On days 1-4 post-SAH, simvastatin-treated rats have significantly improved beam balance scores (days 1-2, p<0.001; days 3-4, p<0.01), beam balance times (days 1-4, p<0.01), and latency to traverse the beam (days 1-3, p<0.01; day 2, p<0.005; day 4, p<0.0001) in comparison with control groups that, conversely, were not protected against SAH-related body weight changes. These results demonstrate that the administration of simvastatin may represent a beneficial therapeutic approach able to reduce post-SAH cognitive dysfunction.

Nanotechnologies for brain tumor therapy

Abstract This chapter introduces a potential definitive treatment in the struggle against malignant brain tumors. In spite of successful steps in biomedical research, brain glioblastomas remain a death sentence in all cases. The difficulty in overcoming the blood–brain barrier (BBB) is the biggest obstacle for chemotherapeutics, which cannot reach the tumor bed as efficacious doses. The advent of nanotechnology could revolutionize the approach to that. Nanoparticles are versatile, thanks to their particular chemical configuration, and are able to go through the BBB carrying drugs or genes targeted against brain tumors. This will improve the efficacy of treatments and reduce also timing and costs of oncological patients. However the application in vivo of nanoparticles in the field of brain tumor treatment remains difficult to realize: their in vitro and in animal toxicity showed controversial results for the human health, and lacks also long-term follow-up.

Nanotechnology and the New Frontiers of Drug Delivery in Cerebral Gliomas

Gliomas amount to about 45% of all primary CNS tumors and 77% of all malignant primary CNS tumors. It is now generally accepted that the modulation of gene expression may be the most effective modality to control specific gene functions correlated to the development and progression of gliomas. The efficacy of current multimodal therapeutic strategies in gliomas is limited by the lack of specific therapies against malignant cells, and the prognosis in patients affected by primary brain tumors is still very unfavorable. Current pharmacological treatments for brain tumors are also limited by the presence of the blood–brain barrier as a natural obstacle to overcome. Thus, therapies for brain tumors are still limited to date. Nanotechnology offers a way to bypass, in a noninvasive manner, the barrier delivering specific therapeutic compounds. Moreover, nanoparticles drug delivery systems can improve bioavailability and sustain release of drugs for systemic delivery. Interestingly, multifunctional nanoplatforms provide multiple functions in a single compound. These innovative compounds are able to deliver drugs in the optimal dose range, which results in augmented therapeutic efficacy and minimal side effects. In this chapter we will focus on the different types of nanoparticle compounds studied for the treatment of brain tumors. Finally, we will report various preclinical and/or clinical studies in brain tumor treatment.

Brief introduction on brain tumor epidemiology and state of the art in therapeutics

This chapter focuses on the epidemiology, epigenetics and therapy of brain tumors. Standard treatment includes maximal surgical resection with postoperative radiotherapy and concomitant and adjuvant chemotherapy. Even with the most advanced multimodal standard treatments malignant brain tumors, namely gliobastomas, still have a poor prognosis. Numerous studies have been performed, and many are still underway, to develop successful treatments, and a major challenge seems to be defining the real cellular origin of this tumor. Starting from the initial cellular mutations and epigenetic modifications it will be possible to find new epigenetic-based therapies. We also stress the importance of overcoming the blood–brain barrier in order to improve the therapeutic effects.

Brain drug-delivery attempts

This chapter discusses the possibilities of therapeutic overcoming of the blood–brain barrier (BBB) by different treatment strategies. Drugs are usually administered via the intravenous route, but the BBB often impedes the intravenously delivered drug in reaching the intracranial compartment. Moreover, the scarce accumulation of drugs in the brain depends also on its rapid clearance by the extracellular fluid and the plasmatic half-life of the drug itself. Nowadays, multiple strategies exist to circumvent the BBB and achieve therapeutic concentrations of drugs in the brain. The intravenous route, for example, shows more efficacy when the drug is linked to a carrier system like polymeric depots, liposomes or lipid carriers. To favor the penetration of drugs inside the brain transporter-independent and transporter-dependent mechanisms have been developed. Genetic engineering is also used to produce monoclonal antibodies and liposomes too are studied for gene therapy.

Nanoparticles potential: types, mechanisms of action, actual in vitro and animal studies, recent patents

The notion of nanotechnology has evolved since its futuristic conception to its current position as a mainstream research initiative with broad applications among all divisions of science. One of the most important clinical applications of nanotechnology will undoubtedly be realized in therapeutics, and the challenge of brain tumor treatment can greatly benefit from it. Their nanometric size along with the electrostatic charge and putative lipophilic characteristics allow nanoparticles to penetrate into the brain tissue freely. Nanoparticles across the blood–brain barrier can represent ideal devices for bypassing that obstacle, becoming the new frontier for successful brain tumor therapy. Intravenous nanoparticles are administered, in experimental settings, as carriers to deliver drugs into the tumor bed. Although promising in vitro results have been reported, it remains unclear how effective such a system would be due to intra- and inter-individual patient heterogeneity. Relevant patents of nanoparticle systems used as drug-delivery carriers are also reported.

Blood–brain barrier pathophysiology in brain tumors

In this chapter we will focus on the blood–brain barrier physiological structure and subsequent pathophysiology in the presence of brain tumors. The existence of the blood–brain barrier selectively prevents the free passage of numerous molecules, especially macromolecules such as many drugs are. The tightness of the barrier is due to its non-fenestrated endothelial cells and junctional structure; the presence of transmembrane proteins sealing the intercellular cleft also plays a pivotal role in the selective passage of substances. In the presence of a pathological process, such as inflammation or brain tumors, the barrier undergoes modifications of its permeability. It is the thorough study of the functioning of the barrier in both physiological and pathological settings that can be the key to interfering with its permeability, and so allowing the passage of drugs.

Future scenarios: nanoparticles and stem cells

Although nanotechnologies hold great promise in glioma therapy, there have been few positive results in the clinical setting so far due to intra- and inter-patient heterogeneity. New models allowing tumor-specific targeting and extensive and safe intratumoral distribution must be developed to efficiently deliver drugs carried by nanoparticles. Laboratory modifications of nanoparticles have been tested to specifically track tumor cells, and a great step forward has been made thanks to the conjugation with neural and mesenchymal stem cells. These stem cells possess a specific tropism for brain tumors which makes them putative candidates as delivery vehicles for nanoparticles in glioma therapy. Stem cells have a natural tendency to migrate and distribute within the tumor mass and they can also incorporate nanoparticles. Stem cell therapy combined with nanotechnology could be a promising tool to efficiently deliver drugs to brain tumors.