[Introduction] [Agenda] [Abstracts] [Recommendations] [Roster]

Introduction

In collaboration with Dr. Jonathan Pollock of the Division of Neurobiology and Behavioral Research (DNBR) and Dr. Joe Frascella of the Division of Treatment Research and Development (DTRD), Dr. Jag Khalsa of NIDA's Center on AIDS and Other Medical Consequences of Drug Abuse (CAMCODA) presented a mini-symposium on Substance Abuse and Neuropsychiatric Disorders at the International Workshop on Brain Banking, March 11-12, 2002. The workshop was organized by Dr. Piotr Kozlowski, a neuropathologist at the National Institute of Neurological Disorders and Stroke (NINDS), (currently Director, New York State Institute for Basic Research in Developmental Disabilities), and co-sponsored by the National Institute on Drug Abuse, and National Institute on Aging of the National Institutes of Health (NIH). More than 60 neuroscientists, neurologists, and neuropathologists presented outstanding research and suggestions for the establishment of brain tissue respositories ("Brain Banks") in the United States and abroad. The mini-symposium participants discussed issues relevant to drug abuse and HIV-related neuropsychiatric and neurological complications and made recommendations for future research (see under RECOMMENDATIONS). The abstracts are being published as a supplement to the Journal of Pathology and Experimental Neurology and a summary of the workshop proceedings is being published elsewhere. The information relevant to drug abuse and HIV infection is summarized below.

In general the participants discussed issues of the need and type of tissue collection, storage, and distribution/shipping. Based on their experiences, they stated that tissues from discrete areas of the brain and every stage of disease are needed for the understanding of pathophysiology of, e.g., Alzheimer's, Parkinson's, schizophrenia or other diseases. A careful dissection of anatomically distinct small regions of the brain is critically important, for example, for the best use of new and sensitive techniques such as massively parallel signature sequencing (MPSS). Further, new techniques also are needed for separating individual cell types since mRNA shows different rates of degradation in different cell populations. But it is also important to note that diseases influenced by a large variety of susceptible genes may require large sample populations. On the subject of tissue collection, it is critical to maintain an excellent symbiotic and collaborative relationship with the local Medical Examiner's (ME) Office and MEs elsewhere in order to collect the post-mortem tissue (whole brain or specific brain areas) in a timely manner and after proper and ethnically sensitive consent from the appropriate relative(s) has been obtained. It may be necessary to educate the ethnically sensitive public in maximizing access to post-mortem tissue for brain research. Publicity may also help in enlisting "control" cases, e.g., brains of non-cognitively impaired famous people following sudden death. It is also essential to use standardized methods of tissue harvesting (timing of collection), preparation, and preservation across as many as ME offices and Brain Banks in the US and abroad. Access to ME cases must be faciliated not just for control cases but because sudden deaths represent, and include, important fields of inquiry, e.g., drug abuse, suicide, neuropsychiatric disorders.

On the subject of storage of brain tissue, it is important to note that a pH of <6 is hypoxic while a pH of >6.4 is considered a better indicator of postmortem (PM) tissue preservation. On the other hand, a wide range of postmortem pH (6.5-7.2) and brain tissue storage has minimal effect on mRNA preservation. Therefore, researchers should be trained in the art of collecting and storing brain tissue, brain tissue handling protocols used by domestic and international brain tissue repositories ("Brain Banks"), and sensitivities and limitations of the current methodology, e.g, microarray technology. Further, in the current genomics age, since there are 30,000-40,000 genes, 100,000 proteins, and 50-70% are expressed in the brain, the human brain tissue is essential for not only determining location and/or function, but also for detecting splice variants. Other critical elements discussed are further elaborated below.

To study the neurological and neuropsychiatric effects of drugs of abuse and or HIV infection, it is important to obtain accurate history and extent of drug exposure because the neurotoxic effects differ with the type of drug. Based on the observation that HIV infection is associated with cognitive impairment/HIV dementia, the role of butyrylcholinesterase (BChE) in Alzheimer's disease and metabolism of cocaine, Royal and his colleagues (see abstract below) successfully examined sections of fixed brain from patients with HIV-related cognitive impairment and from non-infected control subjects, including individuals with Alzheimer's disease, for expression of this enzyme. Their studies further highlight the utility of combining materials for analysis from multiple sources and, therefore, the importance of even more uniform approaches to the procurement, preparation, storage, and distribution of banked materials.

Participants also pointed out that polydrug abuse, that occurs in the real world, should be recognized and investigated as such. Blood samples from each investigated case should be deposited, for example, in the central NIDA-supported repository for genotyping. It is critical to use standardized methods for compiling antemortem clinical data, disease and drug taking histories and toxicology reports; and that clinical data are essential not only for clinicopahological correlation but also for determining subtly different subgroups within patient cohorts. Further, for example, lateral asymmetry between brain hemispheres is important to understand the neuropathological phenotype of drug abuse. Other issues such as gender differences in drug susceptibility and the benefit of newer neuroimaging techniques (MRI, fMRI and PET) were also discussed.