Theorizing Neurodegeneration
The brain and its inner workings remain as mysterious as the deep sea or outer space, in many ways. We know so much about how the human brain functions however the more we learn, the more questions we have. Given this, the world of neurology is a grey area and clinicians/researchers who practice within this realm must have the mental flexibility to approach problem solving without a ‘black or white’ perspective.
Within the world of neurology, epileptology is extremely esoteric and, at first glance, seemingly difficult to conceptualize. Epilepsy is a disorder of the brain where people tend to have recurrent, unprovoked seizures and given that seizures are a manifestation of aggregate neuronal hyperexcitability – we have learned much about how the brain works through the observation of epileptic seizures. Much of neuroanatomy is understood through the observations of patients suffering from stroke (where brain function stops in certain areas causing loss of function) or patients suffering from seizures (where brain function is overexaggerated causing increased function). Over time, we’ve developed an understanding of human neuroanatomy and neurophysiology. We’ve developed an understanding of basically how our mind works.
Do not believe the myth that “people only use 10% of their brains”. I do not know where that came from but it is dead wrong. Think of the brain more as an elaborate system comprising of component parts where each part functions independently. Overall each independent region is regulated by complicated intra-connecting and inter-connecting cortical and subcortical networks to produce a beautifully efficient overall system. In essence, regions of the brain are connected with each other through different pathways as our nation’s electrical grid is connected region to region.
You cannot be a scientist in the biological sciences if you do not ascribe to the theory of evolution. Every living organism on earth is the result of evolution and our brains, one of the highest-ordered thinking organs in life, is likely the most evolved organ that exists. As organisms gain more function, more intelligence - brains become more progressively compartmentalized – higher ordered regions develop on top of more primitive regions while the primitive regions cannot be destroyed. The more evolved the mind becomes over generations in time, the more complicated the cortical networking becomes to connect all the regions together.
The brain is amazingly resilient despite its complicated structure and another way to conceptualize how our brain is structured is through the analogy that follows. John Allman, in his book Evolving Brains (2000), likens the modern human brain to that of a power plant he visited in the 1970s. The old power plant profited from the efficiency brought forth by modern computer technology yet still used obsolete, vacuum and pneumatic technologies as well. When Allman queried about the reasons for this strange mix of old and new technologies in the power plant, he was informed that demand for power was too great for the plant to ever be shut down: “the brain has evolved in the same manner as the control systems in this power plant. The brain, like the power plant, can never be shut down and fundamentally reconfigured, even between generations. All the old control systems must remain in place, and new ones with additional capacities are added and integrated in such a way as to enhance survival.” (Allman, 2000, p. 41).
I think the background provided can allow you all to have a frame of reference to use to understand what happens in many neurodegenerative disorders. If the brain is an amalgamation of regions that are connected through complicated networking, brain dysregulation occurs when there is disruption of this complicated network. Disruption of either regional networking or interregional networking results in dysfunction, so to speak. Parkinson’s develops through the loss of regional dopaminergic networking (in the most simplistic sense). Alzheimer’s develops through loss of generalized cortical/subcortical networking. Certain epilepsies develop through loss of or overrepresentation of regional and/or generalized cortical/subcortical networking.
What causes cortical/subcortical network disruption? In my view, chronic neuroinflammation and the futile cycle of further degeneration caused by more progressive neuroinflammation. Once the neuroinflammatory cascade begins, in essence, it induces further neuroinflammation – a self-fulfilling prophecy, in my view. Targeting the herald steps in the chronic neuroinflammatory cascade, in theory, should be the approach researchers take to solve the mystery of neurodegenerative disorders.
Bashers love to point out how mice studies are insignificant, but when you think about evolution – where mammals share essentially similar tissues/nerves/systems and pathophysiological processes – preclinical data to suggest a drug may stop chronic neuroinflammation means a lot. The same pathophysiological processes exist in humans and further study in humans is worth investigating if there is evidence towards efficacy in preclinical murine models. Mouse models do mean something!
We are still in the beginning stages of understanding neuroinflammation and the disorders associated with this pathophysiological process, despite our relatively “long” time invested in Anavex. I reiterate that time and patience are key if you are comfortable about your investment hypothesis on this speculative, microcap biotech. Patience is a virtue! Have a great Saturday everyone!
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