Background - Neurons are scattered throughout the body and are responsible for sensing and responding to the environment. The nervous system is actually broken down into a peripheral nervous system and a central nervous system. The peripheral nervous system can be further broken down into the somatic and autonomic nervous systems, which regulate voluntary and involuntary actions respectively. While books have been written on the various systems associated with the peripheral nervous system, later blog posts will focus on optimizing the autonomic nervous system to better serve productivity in the workplace. This blog post will focus on the central nervous system, specifically a relatively unknown physiological agent, cerebrolysin. Cerebrolysin is a mix of peptides derived from pigs. In the human body, cerebrolysin acts similarly to endogenous brain-derived neurotrophic factor (eBDNF). BDNF is a naturally occurring protein expressed in many cell types, including neurons in various brain regions. This protein plays a crucial role in synaptic plasticity and neuronal survival.

Synaptic Plasticity - Synaptic plasticity, or the ability of a neuron to strengthen or weaken its connection to another neuron. The most common theory of depression involves the decrease of synaptic plasticity. Because these neurons become "rigid", their responses are fixed, thus promoting a maintained state of depression or lack of pleasure. BDNF is heavily involved in the regulation of synaptic plasticity through pre-synaptic vesicle cycling, or the act of releasing a neurotransmitter into the synaptic cleft. If BDNF protein is low, the pre-synaptic neuron will not release neurotransmitters, which impacts the neighboring neuron, which then impacts the neuron following the neighboring neuron. An example of this would be having a multi-pipe line. If we break the first pipe, the following pipes will be empty. Except in this case, the brain consists of 86 billion neurons and 85 billion nonneuronal cells, which interconnect and interact with each other, so a "break" in any connection can impact a wide region.

Neuronal Survival - Neuronal survival refers to the ability of the neuron to withstand stress and reduce cell suicide, known as apoptosis. Apoptosis can be especially harmful in the central nervous system because neurons regenerate very slowly. Because of the slow regeneration, preservation of any existing neurons is crucial for cognition. BDNF has been shown to increase neuronal density or the number of neurons in a fixed area, and increase survival via downregulating apoptotic pathways.

Mechanism of Action - Since cerebrolysin is a porcine-derived neurotrophic peptide, its actions are extremely similar to human BDNF, thus administration via parental injection may enhance cognition. According to many sources, cereborlysin acts on two main pathways: the first being the neurotrophic pathway, and the second being the sonic hedgehog pathway. The sonic hedgehog pathway regulates neuronal growth, synaptic connectivity, and synaptic plasticity, mainly in the hippocampus but also in other regions of the brain. The neurotrophic factor pathway is also involved in neurogenesis, however, it functions primarily in the protection of existing neurons. Cerebrolysin can bind to receptors on the neurons' surface and activate these pathways, thus resulting in enhanced nueroprotection and connectivity.

Findings in the Literature -
Alzheimer’s Disease - The literature surrounding the use of cerebrolysin for alleviating symptoms of Alzheimer’s disease is limited. However, promising studies have indicated the need for future trials. An umbrella review conducted in 2022 found that cerebrolysin has a significant positive impact on cognition in Alzheimer’s patients, but more data is needed to verify the result. Another study found that administration of cerebrolysin for 28 weeks significantly improved measures of health and cognition, and when combined with donezepil, a more significant improvement was found. It is also repeatedly reported that cerebrolysin administration significantly improves learning and memory in Alzheimer’s induced mice.

Traumatic Brain Injury -  Traumatic brain injury can damage existing neurons, thus rendering them susceptible to neuronal apoptosis. Administration of cerebrolysin has been demonstrated to alleviate this rise in apoptosis, resulting in the prevention of cognitive decline. Another brain injury that is treated by cerebrolysin is acute ischemic stroke. A stroke in the brain is when neurons don’t have access to blood, and because blood carries nutrients, signaling factors, and solvent (water), a loss of access can quickly lead to neuronal apoptosis. Since cerebrolysin acts to protect against apoptosis, its administration protects against the loss of neurons due to stroke. In fact, cerebrolysin is commonly used in the Eastern hemisphere to prevent cognitive decline in stroke patients. In conclusion, cerebrolysin administration should be considered a post-brain injury to prevent the loss of neurons as a result. 

Rehabilitation Post-Drug Abuse - Drug abuse is commonly known to alter brain chemistry and connectivity. Oftentimes, coming clean off of a drug can cause terrible side effects due to an absence of previous drug-induced signaling. Drug abuse can also result in neuronal death due to excitotoxicity. Excitotoxicity occurs when excess signaling occurs and kills the neurons. Too much stimulation can result in neuronal death. All of these factors come into play when the drug is no longer consumed, so the patient can be susceptible to acute pain but also to chronic cognitive decline. This drug abuse does not need to be categorized into hard "street" drugs and common drugs. For example, caffeine addiction is a real thing and can drastically alter brain chemistry. While caffeine consumption promotes health in various ways, excess consumption can lead to problems, and as tolerance builds up, the individual must consume more caffeine, thus increasing the negative effects of caffeine consumption. There are many ways to reset tolerance so that only one coffee can feel what two coffees previously felt like. These practices usually include going cold-turkey, which can lead to undesirable side effects, so an alternative to resetting tolerability is needed. This strategy can be used no matter the compound of choice; adderall, nootropics, caffeine, cocaine, etc. Cerebrolysin administration, as previously described, protects the neurons from dying, so withdrawal will have significantly less of an impact on neuronal health. This retention of neurons allows the individual to stay cognitively inclined and may decrease the probability of relapse. 

Speculation & Cognitive Enhancement - Those looking for an acute cognitive enhancing protocol may include cerebrolysin administration. The effects of administration in a disease model do not always equate to the results of administration in a healthy person. For example, the use of cerebrolysin may protect against neuronal death in Alzheimer’s disease, but when compared to a healthy person, no significant difference is reported. A totally fictional example is provided to help visualize the example easily. Because cerebrolysin has been shown to increase neurogenesis and restore drug responsiveness, it is used to enhance cognitive function in people wishing to improve productivity. Cerebrolysin may be a safer and more effective alternative to common academic drugs such as Adderall or Ritalin. Anecdotal reports have been extremely promising in terms of eliminating postprandial and posttraining brain fog. Standardized self-experiments and randomized trials should be conducted on this work as it could positively impact the well-being of many individuals. 

Dosing - The doses for Alzheimer’s treatment and drug rehabilitation should be adjusted by the physician accordingly. Typical doses for adults range from 5ml to 30ml, whereas a 20ml dose is a typical administration for an individual looking to enhance cognitive productivity. Everyday parental administration is advised and while peptides are usually stored at -20 Celsius, it is recommended to store cerebrolysin at room temperature in the absence of light. For those administering cerebrolysin without the advice of a physician, doses will need to be adjusted to optimize results.

Conclusion - Cerebrolysin is a useful pharmacological agent that is used in a variety of medical situations, including Alzheimer’s disease, Parkinson’s disease, drug rehabilitation, and cognitive decline. Cerebrolysin has shown neuroprotective benefits in humans such that administration protects against neuronal apoptosis and promotes neuronal growth, synaptic plasticity, and synaptic connectivity. Cerebrolysin may enhance cognitive performance outside of neurological disorders, and future studies should be conducted to observe its effect on athletic and academic performance. 

 

A special thanks to the people involved behind the scenes. Without them, these informative and influential posts would not be what they are.
Anna Richardson - Undergraduate
Molly Giblin - High School Student