Despite reports of recovery of function after neural transplantation, the biological interactions between transplanted neurons and the host brain that are necessary to mediate recovery are unclear at present. One source of confusion is in the variety of models and protocols used in these studies. It is suggested that multisite experimentation using standard protocols, models, and recovery criteria would be helpful in moving neural transplantation from the laboratory to the clinic.

It is often presumed that effects of neural tissue transplants are due to release of neurotransmitter. In many cases, however, effects attributed to transplants may be related to phenomena such as trophic effects mediated by glial cells or even tissue reactions to injury. Any conclusion regarding causation of graft effects must be based on the control groups or other comparisons used. In human clinical studies, for example, comparing the same subject before and after transplantation allows for many interpretations of the (...) causes of clinical changes. (shrink)

Neural transplantation as a recovery strategy for neuro-degenerative diseases in humans has used mainly grafting following acute denervation strategies in young adult hosts. Our work in aged mice and rats demonstrates an age-related increase in susceptibility to oxidative damage from neurotoxins, a remarkably poor recovery of C57BL/6 mice from MPTP insult with transplantation and growth factors, even at 12 months of age, and diminished plasticity of host neurons. We believe that extrapolation of data from young adult animal models to aged (...) humans without thorough investigation of transplantation and host response in aged recipients is scientifically and ethically inappropriate. (shrink)

It is well established that neural grafts can exert functional effects on the host animal by a multiplicity of different mechanisms – by diffuse release of trophic molecules, neurohormones, and deficient neurotransmitters, as well as by growth and reformation of neural circuits. Our challenge is to understand how these different mechanisms complement each other.

Cholinergic-rich grafts have been shown to be effective in restoring maze-learning deficits in rats with lesions of the forebrain cholinergic projection system. However, the relevance of those studies to developing novel therapies for Alzheimer's disease is questioned.

Complementation and correction of a genetic defect with CNS manifestations lags behind gene therapy for inherited disorders affecting other organ systems because of shortcomings in delivery vehicles and access to the CNS. The effects of improvements in viral and nonviral vectors, coupled with the development of delivery strategies designed to transfer genetic material thoughout the CNS are being investigated by a number of laboratories in efforts to overcome these problems.

The neural transplantation research described by Sinden and colleagues provides part of the rationale for the clinical application of neural transplantation. The authors are asked to clarify their view of the role of the cholinergic system in cognition, to address extrahippocampal damage caused by transient forebrain ischemia, and to consider the effects of delayed neural degeneration in their structure-function analysis.

In addition to the scientific and medical issues surrounding the use of fetal tissue transplants, the ethical implications should be considered. Two major ethical issues are relevant. The first of these is whether this experimental procedure can be justified on the basis of potential benefit to the patient. The second is whether the use of tissue obtained from intentionally aborted fetuses can be justified in the context of historical and existing guidelines for the protection of human subjects. The separation of (...) ethical decisions from medical practice and scientific research is necessary to prevent the exploitation of innocent human life. (shrink)

Gene therapy approaches have great promise in the treatment of neurodegenerative disorders and malignant brain tumors. Neuwelt et al. review available viral-mediated gene therapy methods and their blood-brain-barrier (BBB) disruption delivery technique, briefly mentioning nonviral mediated gene therapy methods. This commentary discussed the BBB disruption delivery technique, viral and nonviral mediated gene therapy approaches to Parkinson's disease, and the potential use of antisense oligo to suppress malignant brain tumors.

The concept of structure, operation, and functionality, as they may be understood by clinicians or researchers using neural transplantation techniques, are briefly defined. Following Stein & Glasier, we emphasize that the question of whether an intracerebral graft is really functional should be addressed not only in terms of what such a graft does in a given brain structure, but also in terms of what it does at the level of the organism.

Three experiments on neural grafting with adult rat hosts are described. Working memory impairments were produced by lesioning the hippocampus or severing its connections with the septum by ablating the fimbria-fornix. The results suggest that the survival and growth of a neural graft, whether an autograft or a xenograft, is not a necessary condition for functional recovery on a task tapping working memory.

In contrast to the views put forth by Stein & Glasier, we support the use of inbred strains of rodents in studies of the immunobiology of neural transplants. Inbred strains demonstrate homology of the major histocompatibility complex (MHC). Virtually all experimental work in transplantation immunology is performed using inbred strains, yet very few published studies of immune rejection in intracerebral grafts have used inbred animals.

In spite of Stein and Glasier's justifiable conclusion that initial optimism concerning the immediate clinical applicability of neural transplantation was premature, there exists much experimental evidence to support the potential for incorporating this procedure into a therapeutic arsenal in the future. To realize this potential will require continued evolution of our knowledge at multiple levels of the clinical and basic neurosciences.

Resumo: A finalidade deste artigo é bastante pontual e específica: evidenciar os problemas do tratamento acrítico dado à psicologia por Brian Leiter em seu recente Moral Psychology with Nietzsche. O autor inclui, sem se empenhar em qualquer discussão metodológica, a psicologia no rol do que chama de “ciências bem-sucedidas”, tomadas como i) certificadoras do m-naturalismo nietzschiano; ii) dotadas de primazia sobre a própria filosofia na determinação do que é um “raciocínio filosófico” significativo; iii) fornecedoras de um amplo e inconteste corpo (...) de evidências de que a psicologia moral de Nietzsche “está certa” em relação a teses profundamente complexas. Minha exposição consiste em mapear a construção conceitual desse m-naturalismo, e, posteriormente, evidenciar que não há, na psicologia empírica contemporânea, nada próximo da caracterização pretendida por Leiter.: This article has a very specific purpose: to highlight the problems of Brian Leiter's uncritical treatment of psychology in his recent Moral Psychology with Nietzsche. The author includes, without engaging in any methodological discussion, psychology in the list of what he calls "successful sciences" as certifiers of Nietzschean m-naturalism; ii) as endowed with primacy over philosophy itself in determining what is meaningful "philosophical reasoning"; iii) as providing a broad and uncontested body of evidence that Nietzsche's moral psychology “is right” in profoundly complex theses. My expository strategy is to map, initially, the path taken by Leiter in the conceptual construction of his m-naturalism, and, later, to show that there is nothing in contemporary empirical psychology that legitimizes Leiter’s characterization. (shrink)

The lesion and transplantation data cited by Sinden et al., when considered in tandem, seem to harbor an internal inconsistency, raising questions of false localization of function. The extrapolation of such data to cognitive impairment and potential treatment strategies in Alzheimer's disease is problematic. Patients with focal basal forebrain lesions (e.g., anterior communicating artery aneurysm rupture) might be a more appropriate target population.

This article builds on ideas presented in Klein (2015a) concerning the importance of a more nuanced, conceptually rigorous approach to the scientific understanding and use of the construct “memory”. I first summarize my model, taking care to situate discussion within the terminological practices of contemporary philosophy of mind. I then elucidate the implications of the model for a particular operation of mind – the manner in which content presented to consciousness realizes its particular phenomenological character (i.e., mode of presentation). Finally, (...) I discuss how the model offers a reconceptualization of the technical language used by psychologists and neuroscientists to formulate and test ideas about memory. (shrink)

I argue that academic psychology’s quest to achieve scientific respectability by reliance on quantification and objectification is deeply flawed. Specifically, psychological theory typically cannot support prognostication beyond the binary opposition of “effect present/effect absent”. Accordingly, the “numbers” assigned to experimental results amount to little more than affixing names (e.g., more than, less than) to the members of an ordered sequence of outcomes. This, in conjunction with the conceptual under-specification characterizing the targets of experimental inquiry, is, I contend, a primary reason (...) why psychologists find it difficult to discriminate between competing, explanations of the effects of mind on behavior. Absent well-specified theory capable of enabling precise and detailed quantitative prediction, inferring underlying mental mechanisms from experimental outcomes becomes a difficult, if not impossible, task. (shrink)