a-stainless-protocol-for-high-quality-rna-isolation-from-laser

A Stainless Protocol for High Quality RNA Isolation from Laser Capture Microdissected Purkinje Cells in the Human Post-Mortem Cerebellum

Laser capture microdissection (LCM) is an advantageous tool that allows for the collection of cytologically and/or phenotypically relevant cells or ...

Yale University

A review of the brain banking literature reveals a primary focus either on the factors that influence the decision to become a future donor or on the brain tissue processing that takes place after the individual has died (i.e., the front-end or back-end processes). What has not been sufficiently detailed, however, is the complex and involved process that takes place after this decision to become a future donor is made yet before post-mortem processing occurs (i.e., the large middle-ground). This generally represents a period of many years during which the brain bank is actively engaged with donors to ensure that valuable clinical information is prospectively collected and that their donation is eventually completed. For the past 15 years, the Essential Tremor Centralized Brain Repository has been actively involved in brain banking, and our experience has provided us valuable insights that may be useful for researchers interested in establishing their own brain banking efforts. In this piece, we fill a gap in the literature by detailing the processes of enrolling participants, creating individualized brain donation plans, collecting clinical information and regularly following-up with donors to update that information, and efficiently coordinating the brain harvest when death finally arrives.

Banking brains: a pre-mortem "how to" guide to successful donation.

In numerous case-control studies, essential tremor (ET) has been associated with cognitive impairment. ET is often familial. However, cognitive impairment has not been studied in family members of ET cases. Endophenotypes are measurable clinical characteristics that may be present in individuals with increased risk for disease; as such, they may be present before disease onset. We administered a global cognitive screen to first-degree relatives of ET cases (FD-ET) and age-matched controls (Co).

More unaffected first-degree relatives of essential tremor cases have mild cognitive deficits than age-matched controls.

Tremor is an involuntary, rhythmic, oscillatory movement of a body part. It is a central feature of a range of diseases resulting from pathological changes in the cerebellum. Interestingly, in modern times, the terms "cerebellar tremor" and "intention tremor" are often used synonymously and interchangeably. However, "cerebellar tremor" (i.e., tremors of cerebellar origin) do not always present exclusively as intention tremor. In this article, we comprehensively revisit the clinical phenomenology of tremors observed in various diseases that are based in the cerebellum. By this, we mean diseases for which the cerebellum and its various connections are often seen as playing a central and defining role. These include spinocerebellar ataxias, essential tremor, orthostatic tremor, dystonia, acute cerebellitis, cerebellar tumors, paraneoplastic cerebellar degeneration, and cerebellar strokes. The theme of this article is to highlight, through published data available in the current literature, that the clinical phenomenology of tremor of cerebellar origin is heterogeneous, and it extends beyond that of intention tremor to include postural tremors, kinetic tremor, rest tremor, and orthostatic tremor. This heterogeneity is consistent with the seminal work of Gordon Holmes, in which he described a variety of tremors aside from intention tremor in the setting of cerebellar lesions. In the end, it would seem that the notion that intention tremor is the sole signature of cerebellar lesions is an over-simplification and is not correct. Future studies are warranted to identify and further characterize the heterogeneity of tremors arising from the various cerebellar etiologies.

Elan D. Louis

Yale University

A Stainless Protocol for High Quality RNA Isolation from Laser Capture Microdissected Purkinje Cells in the Human Post-Mortem Cerebellum