Postmortem brain samples

Careful sample selection and preparation are the prerequisites for a successful analysis (Boguski and McIntosh, 2003). Postmortem brain samples for our studies were obtained from the M RC London Brain Bank for Neruodegenerative Diseases, Institute of Psychiatry. The AD patients fulfilled the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer s Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD (Mirra et al., 1991). A definite diagnosis of AD was performed by historical analysis of the brain samples, which was consistent with the CERAD criteria (Tierney et al., 1988). The brain regions temporal, frontal, occipital, parietal cortex, and cerebellum of patients with AD (72.3 7.6 years old) and controls (72.6 9.6 years old) (Seidl et al., 1997) were used for the studies at the protein level. The... 

Bo tiles or containers found near victim, even if em pty Exam inatio n of cloth ing if stained orifodoursaie noted Antemortem examination ofbbod or urine samples Postmortem examination oflungand brain specimen , also vitreous humour, espe daily if the body is decomposed... 

Meador-Woodruffetal. (1997) quantified the levels of mRNA molecules encoding the five dopamine receptors in postmortem brain samples from 16 schizophrenic patients and 9 control subjects and found a dramatic decrease of dopamine recep tor transcripts in the prefrontal cortex but restricted to the D3 and D4 receptors and localized to Brodmann area 11 (orbitofrontal cortex). No differences were found in striatum or visual cortex. 

Postmortem human brain tissue is obviously not subject to as rigorous control as experimental tissue from laboratory animals. As such much care needs to be taken when attempting in situ hybridization with human brain. In addition to the normal factors such as age and gender that need to be controlled with human samples, other factors, such as the immediate premortem state of the individual, the time taken for tissue recovery, and the storage conditions, must also be considered (for review, see Hynd et al., 2003). 

The proteomic analysis of the brain has certain limitations that are related either to the sample and/or analytical approach. In the analysis of the brain, many factors may be involved, such as differences among individuals, differences in age and sex, possible other diseases, treatment with medicines, as well as technical factors, disease-unrelated factors, such as postmortem time, improper treatment of the samples, etc., all of which can affect a clear discrimination between healthy and diseased states of interest. The technical limitations involve inefficient detection of low-abundance gene products, hydrophobic proteins (they do not enter the IPG strips), and acidic, basic, high-, and low-molecular mass proteins. All these protein classes are underrepresented in 2-D gels (Lubec et al., 2003 Fountoulakis, 2004). A combination of proteomics methods with protein separation, enriching techniques, and alternative methodologies for detection will improve the detection of additional differences between AD and control brains. Such differences may be essential in the discovery of early disease markers and therapeutic approaches. 

This is particularly useful when investigating deaths due to solvent abuse, e.g. toluene or chloroform, because of the high concentrations that these substcmces attain in the brain [Pg.113]

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