The non-human primates (NHPs)—macaques, baboons, and chimpanzees—have always been biomedical subjects, with the same genes and bodies as us. Probably the most interesting NHP biology study in neuroscience concerns the chemistry of CSF. CSF lubricates the CNS—drives the brain, excretes waste, and relays messages from the brain to the spinal cord.
CSF is used to understand brain activity, neurological disease, and treatment response in NHP animals. I write about NHP biologicals—CSF—in this blog to help our understanding of the brain and brain diseases like Alzheimer’s, Parkinson’s, and multiple sclerosis. It also discusses NHP CSF drug discovery, biomarker discovery, and experimental models.
What is Cerebrospinal Fluid (CSF)?
Cerebrospinal fluid is an aqueous fluid around the brain and spinal cord. Made mostly by cells in brain ventricles (called the choroid plexus), CSF has many purposes:
Protective: CSF protects the brain and spinal cord from acute traumatic external causes, like a shock absorber.
Homeostasis: It controls the chemical state of the CNS so the nerve cells can work properly.
Exhaustion: CSF excretes metabolic byproducts from the brain, which is a central component of neurodegenerative disease.
Delivery of nutrients: It conveys nutrients, hormones, and other important molecules to the CNS.
Because the CNS is entirely dependent on it, the analysis of primates’ CS—and even human-transformed primates—offers much insight into how the brain works and why disease does or does not occur.
NHP Biologicals: Why Aren’t Human Primates Employed in CSF Research?
It is only because
Like Humans: NHPs have 98-99% of their DNA in common with humans, which means they make perfect human disease and brain models.
Design and Function of the CNS: Because NHP brains are similar in size, shape, and function to human brains, we can more easily model human neurology.
Applying to Disease Models: NHPs are especially well suited to models of CNS conditions like Alzheimer’s, Huntington’s, and stroke, and to study potential treatments.
If NHPs could be gathered and tested, then scientists could put animal models to use in understanding diseases in humans—and the results would be more translatable. The NHPs’ CSF can be repurposed for disease biomarkers, protein counts, and other molecular signatures that help us orient ourselves on more complex neurological states.
What Can NHP CSF Do in Neuroscience?
Even NHP cerebrospinal fluid is improving the majority of neurological conditions scientifically. Here are some of NHP CSF’s most useful applications:
1. Neurodegenerative Diseases
There are neurodegenerative disorders like Alzheimer’s disease (AD) and Parkinson’s disease (PD), brain diseases in which neurons have died. They are both tricky to detect and tricky to diagnose: early biomarkers exist only in trace amounts in blood or brain tissue.
NHPs are neuroanatomically and physiologically similar to us, and so are perfect lab animals for these conditions. In the CSF of NHPs whose brains have been induced with neurodegenerative disease, scientists can discover new biomarkers that might also be present in pre-disease human cases.
Alzheimer’s disease: Samples from NHPs confirmed high levels of AD-associated proteins such as amyloid-beta and tau in CSF. They could potentially count these in NHP CSF and track their spikes as patients went brain-dead, searching for targets to treat.
Parkinson’s Disease: Dopamine depletion is a PD signature, and since dopamine levels have fluctuated in NHPs’ CSF, scientists can follow the progression of the disease. We also looked for CSF biomarkers like alpha-synuclein for PD.
2. Drug Delivery Through the Blood-Brain Barrier and Central Nervous System.
The BBB is a selective permeability layer that encases the brain from corrosive chemicals and restricts the flow of nutrients. However, the BBB is also an issue for the delivery of drugs in CNS diseases. We have all sorts of promising drugs, but they fail at the BBB and don’t do anything.
The NHP models teach us about BBB and drugs. NHPs need CSF studies to understand how drugs travel and if they function in the CNS. If they can find out what drugs do to CSF shape or how much of the drugs are in the CSF, then they can work out how to maximize delivery through the BBB and create new treatments for stroke, epilepsy, and brain cancer.
3. Neuroinflammation and Immune Response
There is a shared neurological comorbidity between neuroinflammation, multiple sclerosis (MS), and traumatic brain injury (TBI). It’s this link between the immune system and the brain that will allow treatments to control inflammation without compromising the brain.
We can also study the immune system of the CNS with CSF. NHP CSF can be compared with immune cells and cytokines to examine inflammatory brain conditions. If these are monitored, researchers will understand how neuroinflammation drives disease and find new targets for cures.
4. Cerebrospinal Fluid Biomarkers
That’s the aim of NHP CSF research—to be able to diagnose, monitor disease evolution, and evaluate the efficacy of treatment. They are specifically seeking proteins, lipids, and RNA molecules that might be present in large quantities in the CSF of neurologically affected animals.
In NHPs, for example, we already have Alzheimer’s, Parkinson’s, and other neurodegenerative markers. These biomarkers don’t only have diagnostic utility; they can also be used to disentangle disease physics at the molecular level. This could be used to begin clinically creating these types of biomarkers in humans with NHP CSF.
Strength to Take in and Throw Out NHP CSF.
NHPs are a blessing for CSF research, but obtaining and processing CSF from these animals is not easy.
Interventions involving invasive procedures. Only by lumbar puncture (spinal tap) or cisternal puncture can CSF be expelled from NHPs. These are possible but unsafe and need to be kept in check.
Moral Issues: Animals are in the game when it comes to NHP studies. It’s up to scientists to make sure every experiment is ethically acceptable so that no harm is caused and the experiment is a lot more worthwhile than the harm to the animals.
CSF chemistry is unstable: As with all liquids, the CSF chemistry varies from person to person, species to species, and even animal to animal. This variation makes the results unintuitive and demands a well-designed study and sampling.
Complexity of CSF Analysis Technology: High-end instruments and technologies are applied to study the CSF, such as mass spectrometry, enzyme-linked immunosorbent assays (ELISA), and proteomics. This type of analysis requires special tools and knowledge, and so CSF research is costly.
Conclusion: The Road a Long Way—NHP CSF in Biomedical Science!
The brain, neurological illness, and cure are still being reimagined by non-human primate CSF. There’s so much that we can know about complex diseases that we just can’t replicate in small animals or people with NHPs. NHPs’ biological and genetic diversity gives researchers an attractive environment to discover new biomarkers, disease mechanisms, and new treatments for neurological disorders.
As better ways to get CSF extracted and analyzed are found, and animal ethics mandates we need more animals to experiment with, NHPs’ role in neuroscience will only continue to grow. Because NHP biologicals—and especially the CSF study—will let us carve out new doors for the war on neurological disease and reduce, one pain at a time, the world’s millions of patients.
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