Discovery
NRPs were discovered using a phenotypic brain tissue assay that screens to find compounds that provide neurogenesis in vulnerable brain tissue. The phenotypic cell proliferation / migration assay was using purified hippocampal metabolized cell supernatant from rats.
What Dr Sieg discovered was the development of a thalamic regenerating cell-bridge after NRP administration as illustrated below:
To our knowledge, no other group has achieved such a cell-bridge spanning over 3 mm from the thalamus to the visual cortex with any other compound. This was the first hint that NRPs could be a powerful neuronal regeneration drug hence the name N (Neuronal) R (Regeneration) P (Peptides) ~ NRPs.
What does it really mean?
This discovery confirms for the first time that highly susceptible thalamic tissue has neural stem cells that can be differentiated into neural precursors that acquire neuronal phenotypes. These inhibitory migrating cells are vulnerable to hypoxia and excitotoxic stress and are diminished during states of encephalopathy as well as within other brain diseases.
The above diagramme shows the proliferation and migration of parvalbumin-positive neurons in the sprouting area of the thalamocortical axis after Neural Regeneration Peptide (NRP) administration. Arrows in A/B show double-positive cells for parvalbumin (A) and MAP-2 (B) within the thalamic migrating cell stream.
Conclusion
In conclusion, NRP molecules have neuro-regenerative potential on inhibitory thalamic neurons. This particular area in the brain of Lennox-Gastaut patients is deprived of these neurons and is highly dysfunctional. Re-establishment of these neurons with adopted neuronal function will lead to seizure cessation and memory stabilisation.