The BTRs serve as biospecimen source sites for the collection of brain, other relevant tissues, and fluids from postmortem donors. Each NBB BTR has trained staff who conduct rapid recovery and processing of postmortem specimens.

The brain is removed from the calvarium, weighed and photographed. After the brain has been removed, the olfactory bulbs and, when possible, cerebrospinal fluid (CSF) and a portion of the cervical spinal cord are retrieved. In addition, some BTRs collect and bank other tissue specimens including skin and samples from other organ systems. Postmortem blood is sampled and submitted for serology and toxicology testing.

Quality control measures are initiated at the time of biospecimen collection and include documentation of agonal state and postmortem interval, standardized sectioning, processing and storage of the brain and related tissues/fluids, completion of a standard neuropathology assessment, and measurement of the RNA Integrity and pH.

The BTRs use comparable collection, processing and storage protocols. In general, one hemisphere of a brain is fixed either with formalin or 4% paraformaldehyde, and the other hemisphere is flash frozen. However, both fixed and frozen tissues are not always available from every brain.

The BTRs use standardized templates for dissection and matching of select anatomic regions by personnel trained in human brain anatomy. Regions of interest are sampled from a series of hemi-coronal slices of fixed or frozen brain tissue for distribution to end-users.

All brain specimens donated to the NIH NBB are assessed and reviewed by board-certified neuropathologists. A standard assessment is performed to document possible neuropathologies and to establish diagnosis of disease condition. Gross inspection of the brain includes assessment of regional atrophy and inspection of macroscopic lesions and blood vessels for vascular disease. Brains are photographed in multiple planes to document the gross features and macroscopic abnormalities of each donation.

In the first step, the clinical presentation of each donor is reviewed along with a screening assessment of the brain. Following gross examination of the brain, watershed territories (Brodmann areas 4,3,1,2), basal ganglia and cerebellum are sampled, H&E (hematoxylin-eosin) are stained and microscopically evaluated. For all donors ≥65 years of age the screening protocol is followed by the full neuropathological assessment described below.

For donors below age 65, clinical assessments are reviewed for any indication of brain-related disorders with known physical impact on the brain. If clinical evidence for such disorders is identified, the brain receives a full disease-appropriate neuropathological assessment. If the review of the clinical history does not endorse the presence of discernable neuropathology, then, the neuropathological screening protocol is implemented to rule out unsuspected pathology. If this screen reveals any indication of neuropathology, then a full evaluation is performed using stains for the indicated neuropathology. If there is no clinical history of a brain disorder with identifiable histopathology or systemic disease with neuropathological consequences, and the neuropathology screen confirms the absence of any pathologic process, then the neuropathological assessment is determined to be complete.

Neuropathological assessment of brains from aged persons (≥5) or donors with a clinical diagnosis of neurologic disease are examined with immunohistochemistry performed in multiple brain regions, including: superior and middle frontal gyrus, orbital cortex, watershed territories (Brodmann areas 4,3,1,2), basal ganglia with basal forebrain, amygdala, hippocampus (rostral and caudal levels with adjacent amygdala, parahippocampal and inferior temporal cortex), superior temporal gyrus, parietal cortex (angular gyrus), calcarine cortex, hypothalamus with mammillary bodies, thalamus, substantia nigra, midbrain at the level of the SN, pons including LC, medulla including DMV, cerebellar vermis, lateral cerebellar hemisphere and cervical spinal cord.

Histochemistry and immunohistochemistry can include, but is not limited to: H&E, modified Bielschowski, thioflavin S, anti-beta-amyloid, alpha synuclein, phosphorylated tau and TDP-43. Cerebrovascular pathology is assessed using an adaptation of the protocols described by Vinters et al., 2000. The vessels of the circle of Willis are photographed and evaluated semiquantitatively. The extent of arteriosclerosis is also assessed semiquantitatively. Congophilic angiopathy is rated using the criteria developed by Vonsattel, et al., 1991. Ischemic lesions are tabulated and mapped as: cystic infarcts; lacunar infarcts; and microinfarcts. The hippocampus is evaluated separately for sclerosis.

Following the completion of the neuropathology evaluation, a report is generated indicating major neuropathological findings. This report is available to researchers and to the donor's family / next-of-kin, by request.

All requests for brain and tissue specimens are placed through the NIH NeuroBioBank website. Following review and approval by NIH and NeuroBioBank staff, one or more of the repositories will fill the request based on specimen availability. If questions arise, the requestor is contacted to clarify and confirm study design.

Although there is no fee for specimens from the NIH NeuroBioBank, end users are required to provide an account number with a shipping carrier to cover the costs of shipping the approved specimens. Shipping usually occurs between 4-6 weeks following approval; however, large requests may take longer to process. If the shipment is intended for a foreign country, the researcher is responsible for obtaining the required documents for entry of biohazardous material.