Table 1. Trade-offs among the methods discussed for brain banking.

This table summarizes the key advantages, disadvantages, evidence level for each of the different methods discussed in this review that can be used for long-term brain banking and neuroanatomical preservation. In the "Evidence Level" column, "Moderate", "Low", and "Minimal" describe the relative abundance of supporting scientific literature for each preservation method.

Method	Upsides	Downsides	Evidence Level
Aldehyde-based fluid preservation	• Simple and inexpensive • Generally good reported morphologic preservation, although potential for artifacts • Proteins and most other molecules are expected to be retained	• Overfixation causes antigen masking and chemical changes • Acidity can damage tissue • Extraction of a subset of lipids, small molecules, and other molecules that are not directly crosslinked	Moderate
Buffer-based fluid preservation	• Simple and inexpensive • Mitigates overfixation • Likely less acid formation over time	• Much less data for morphological preservation over decades of storage • Microbial contamination without biocides	Low
Alcohol-based fluid preservation	• Widely used long-term fluid preservative agent • Mitigates overfixation • Antimicrobial effects	• Tissue and cell shrinkage • Biomolecular extraction • White matter cavity formation • Highly flammable and hazardous	Low
Fluid preservation after tissue clearing	• Allows imaging of intact specimens • Minimizes lipid-associated oxidative damage	• Delipidation causes biomolecular information loss • Novel methods without long-term track record	Minimal
Cryoprotectant-based fluid preservation	• Mitigates overfixation • Limits biomolecule extraction • Easy conversion to cryopreservation	• Chemical changes still occur in biomolecules • Tissue penetration is slow • Risk of osmotic damage	Low
Cryopreservation (sub-zero temperature)	• Best antigenicity preservation • Allows for compatibility with molecular biology techniques used on fresh tissue • Potential for function preservation	• Ice artifacts can occur in absence of complex vitrification protocols • Thermal stress damage for large specimens • Highest cost	Moderate
Paraffin embedding	• Avoids overfixation, excellent antigen preservation • Excellent morphology preservation • Minimal chemical reactions occur during storage	• No protocols yet established for intact human brains • Paraffin processing requires high temperature that can damage tissue • Biomolecular extraction	Moderate
Resin embedding	• Allows for highest quality ultrastructural imaging possible • Can retain more lipids if osmium post-fixation is used • Minimal chemistry during storage	• Usually performed on tiny samples, not close to human brain scale • Chemicals used tend to be expensive • Biomolecular extraction	Low