The Unsuspected Intrinsic Property of Eukaryotic Cell to Dissociate the Water Molecule. Implications in the Context of Brain Ventricles Volume

Ventricular system is located deep inside brain and reflect the overall process of parenchymal tissue. Brain ventricles have been reported to be enlarged in several neuropsychiatric disorders and in aging [1]. It had been reported higher brain ventricle volume in psychiatric disorders such as depression [2], anxiety [3], and bipolar disorders [4]; dementia [5]; general cognitive decline [6], advanced aging [7]; Rett syndrome [8]; neurodegenerative disorders such as Alzheimer's disease [9], amyotrophic lateral sclerosis [10], cortical basal ganglionic degeneration [11], multiple sclerosis [12], Huntington's disease [13], and Parkinson's disease [14], and herpes simplex encephalitis [15]. Brain ventricle enlargement currently performed to be due to the loss of neurons and/or glia, including cell death due to microglia activation and neuroinflammation [16]. Cerebrospinal fluid secretion is not given importance. 

Whether human cerebral ventricular volume can decrease over time with psychiatric treatment is not known. We can think that the increase in the volume of the ventricles, often asymmetrical, is common in frequently neurological diseases, after head trauma, and exposure of human being to extreme or abnormal conditions. Astronauts subjected to long-duration spaceflight also appear to have exhibited brain ventricle enlargement over time, whereas controls did not [17]. Supposedly, the headward fluid shift that occurs in space [18], could lead to anterior movement of the Optic Nerve Head (ONH), optic chiasm, and globe flattening. The support for this theory is that in healthy individuals, optic disc edema has been shown to develop after 30 days of strict head down bed rest, that is, simulated microgravity [19]. 

Unique and distinctive clinical and imaging findings occur in astronauts both during and after short and long duration space flight [20]. Some of already described clinical findings post flght, we have unilateral and bilateral optic disc edema (variable Frisén grades), globe flattening (as defined qualitatively on imaging), choroidal and retinal folds, hyperopic refractive error shifts (>0.75 D), or focal areas of ischemic retina (i.e., cotton wool spots). Jugular venous distention also has been well documented during both head down and Microgravity (MG) studies [21]. 

Interestingly, Astronauts grow up to two inches in the space (Figures 1 and 2).

Figure 1: Choroidal folds around the optic nerve (up), corroborated by coherence optical tomography (below). The choroidal folds described in astronauts (pictured, above) are indistinguishable from folds caused by other diseases. 

Figure 2: Choroidal folds in a case of pesticides toxicity.

A rapid growth of BVV occurs during the 1^st year of life before reaching a plateau phase of slower growth thereafter. The plateau phase was preceded by a slight (less than 3 mL) decrease in volume among the higher percentiles in the combined and male growth curves. The Subventricular Zone (SVZ) is also interesting, as it has been identified as a highly neurogenic region of the adult brain [22], so close of the CSF.

• The choroidal plexuses 

The choroid plexus consists of four distinct tissues found deep inside the brain. Together, they’re an important source of the cerebrospinal fluid, or CSF, that bathes the brain and spinal cord. The CSF surrounds the brain and circulates inside it through four channels called ventricles. Each ventricle has its own stretch of choroid plexus tissue, anchored like a kelp bed, its pink fronds undulating in the circulating fl. A century ago, that the “father of neurosurgery,” Harvey Cushing at the Peter Bent Brigham Hospital in Boston, and his contemporary, Walter Dandy, determined that the choroid plexus is a key source of CSF. 

The blood-brain barrier is a boundary that blocks many cells and molecules, as well as pathogens, from entering the brain’s blood supply. The barrier provides vital protection, but it also robs the brain of the blood-cleansing services provided by organs like the kidney and liver. The choroid plexus is quite sensitive to imbalances in CSF health and can activate a rapid response to brain emergencies. Certain cells within the choroid plexus express the same genes that are turned on in kidney and liver cells. In the brain, the choroid plexus is one of the gatekeepers for immune cells can’t get past the blood-brain barrier to attend to the damage. Like the CSF, the choroid plexus has been relegated to the back burner for much of the last 40 years, overshadowed by the neuron cells, which is where the action is, because the availability of powerful tools for studying their electric impulses. The humble cells of the choroid plexus are not neurons, so the choroid plexus has historically been neglected in neuroscience, (Figure 3) and even more so its pigmentation. 

Figure 3: An embryonic choroid plexus, with arrows showing a developing vein (left) and artery (right). (Dani et al., Bioxriv 2019. DOI: 10.1101/627539.) Retrieved from https://answers.childrenshospital.org/choroid-plexus/, on September 18, 2024. 

The genes expressed in the choroid plexus tissue in one ventricle are different from those expressed in a different ventricle, as is each ventricle has its own choroid plexus character. The configuration of the choroid plexus blood vessels of the ventricles is like the arrangement of the blood vessels (and melanin pigment) in the choroid layer of the human eye (Figure 4), since both tissues are characterized by their high content of blood vessels and melanin, approximately 40% more than in the skin.

Figure 4: The arrangement of blood vessels in the choroid of the human eye, in a living patient, closely resembles the arrangement of blood vessels shown in the figure above. The similarity is mostly observed in the lower region (orange star). 

Hydrocephalus, a relatively common progressive increase of fl within the ventricles that can damage the brain, enlarge the head, and even lead to death. Sometimes called “water on the brain,” hydrocephalus can be caused by overproduction of CSF by the choroid plexus (Figures 5 and 6), a blockage of CSF flow, or failure of the bloodstream to absorb CSF at the same rate it’s being produced. 

In infants with hydrocephalus, the excess CSF accumulated within the ventricles can cause brain damage and other problems. For more than 50 years, the standard treatment has been to insert a shunt - a tube that allows excess CSF to drain from the brain into the abdomen, where it’s absorbed by the body. However, shunts often require multiple follow-up surgeries, which are difficult for patients who don’t have easy access to major hospitals.

Figure 5: Photograph of a choroid plexus (blue arrowhead), taken on a living patient, during a Choroid plexus cauterization procedure. The brown color of the tissue is given by its high melanin content. 

It is interesting that when the choroid plexus is cauterized, both in the ventricles and in the human eye, that also has a choroid layer (Figures 6 and 7), the tissue responds by increasing its melanin content.

Figure 6: Histological section of a human eye, showing the choroidal layer on the left (orange arrow). The numerous dark spots of irregular shape and size observed in the photograph, correspond to intracellular melanin granules. The parallel collagen fibers of the sclera are observed at the right of the microphotography.

Organic molecules that dissociate water molecules

2H₂O _(liq) → 2H_{2 (gas)} + O_{2 (gas)}

Chlorophyll, hemoglobins, myoglobins, bilirubine

2H₂O _(liq) → 2H_{2 (gas)} + O_{2 (gas)} → 2H₂O _(liq) + 4e^-

Melanin, neuromelanin, lignin

Figure 7: The dark dots correspond to Laser cauterizations of the choroid of the human eye, live. These characteristic scars of Laser burn typically increase the presence of the pigment melanin in the treated areas. 

The function of melanin pigment inside and outside the cells, is the transformation of the light power into chemical energy susceptible to be used by living beings. And in the case of the choroidal plexuses of the ventricles, the dissociation and reforming of the water molecule explains the secretion and reabsorption of the CSF, since they are chemical reactions that vary depending on the amount of light, pressure, temperature, Body posture, time of year. etc., and depending on the sum of the different variables involved, the dissociation or reforming of the water is favored, which explains the variable behavior of the CSF dynamics, both in health and in disease (Figure 8).

Figure 8: Currently, the interpretation of the increase in volume of the cerebral ventricles is interpreted as first atrophying the brain tissue, and the space that is formed is simply occupied by the CSF. The current, relatively passive role of the CSF needs to be reconsidered, as its biodynamics are determined by the rate of water dissociation and reforming turnover, which we can consider to be the origin of life (and of the CSF). 

But now it must be interpreted as that the brain tissue secondarily atrophies because the dissociation of the water that normally occurs inside the melanin contained in the cells that make up the choroid plexus, is not happening with the appropriate turnover rate, that is, in the range of nano and pico seconds, so the water from the CSF begins to accumulate and has a mass effect on the adjacent tissue. Which does not tolerate this pressure very much because at the same time, brain tissue does not receive the amount of oxygen and hydrogen (from the dissociation of water) sufficient for adequate function and resilience, so the tissue loses its shape and function, and eventually ends up disappearing. 

Since a significant part of the dynamics of the CSF takes place in the choroid plexuses, that is: secretion and reabsorption, or in other words: dissociation and reformation of water; therefore, it is no coincidence that the choroid plexuses could be affected or very altered when the BVV modifies significantly its size.

• CSF secretion and reabsorption 

The dissociation of water that occurs within melanin and other organic molecules derived from protoporphyrin IX (PTP IX) is an amazingly accurate process, so it is relatively easily disturbed by contamination of water, air, and food. A frequent manifestation in the Central Nervous System is the increase in volume of the cerebral ventricles, as in astronauts. But sometimes, rarely; the alteration of the secretion and absorption of the CSF is so skewed that the ventricles are almost collapsed, as in the following case of a female patient (Figures 9-17) who was born with neurological alterations compatible with the diagnosis of congenital agenesis of the corpus callosum.

 Figure 9: The lateral ventriculus are observed with decreased volume, but the choroid plexuses are in good condition.

Figure 10: The volume of the ventricles and even the cerebral fissures are reduced. The Choroidal plexuses look in good shape.

 Figure 11: Clinical photograph of the patient. 

Figure 12: The anatomy is relatively well preserved.

 Figure 13: The dark areas correspond to the hypotrophic areas of the corpus callosum region.

Figure 14: It seems as the secretion of CSF is impaired.

Figure 15: The ventriculus are almost collapsed, however, the choroid plexuses are in good shape, therefore, although brain functions are affected, neuroanatomy is relatively preserved, with the most affected parts being those near the ventricles.

 Figure 16: The choroid plexuses and neuroanatomy are well preserved. 

Figure 17: The regulation of body temperature also depends on the dissociation and reforming of water molecules inside each cell. And the moderate decrease in temperature (35.2 ^°C) is a consistent finding with the neurological picture. 

We might think that the secretion and reabsorption of CSF were compromised in advanced stages of pregnancy by accidental overexposure to environmental pollutants, mainly in water; so the amount of oxygen and hydrogen (energy) was not enough for the complete development of the corpus callosum region. 

The findings reported in astronauts, both in the CNS and in the optic nerve, choroid, and retina, could be explained by the changes that occur in the dissociation and reforming of water under conditions of weightlessness, pressure, temperature, and above all the difference in the amount of light that the human body receives within the atmosphere and in outer space. The scattering of light that occurs within the atmospheric conditions, thereby the human body is more uniformly illuminated. Interpreting the clinical and para-clinic findings based on the dissociation of water as the very first reaction of life, leads us to a different understanding of the evolution and treatment of these patients, allowing us different but significantly more efficient treatments, since they are more in accordance with an anatomy, physiology and biochemistry more congruent with reality.

The dogma that our body works from the graduated oxidation (combustion) of glucose originated from the simplest observation of the functioning of house chimneys, which were and are abundant in cold cities as Paris and London. In the mid-eighteenth century, when it was identified that one of the gases produced by the combustion of wood was CO₂, and the body also expelled CO₂ during expiration, so, it was inferred that, just as wood burns and produces CO₂, then our body also burns something to generate CO₂ from respiration. And some time later, glucose was chosen as the ideal substrate, for wood is in a way a polymer of L- glucose units. And if both animals and humans look for food that contains D-glucose, the universal precursor to any organic molecule, in both plants and animals, then the puzzle seemed solved, both chimneys and lungs work in the same way. But comparing the functioning of the lung with that of a chimney is not even approximate, so the explanation of how the fire in the chimney takes oxygen from the air and therefore our organism as well, required a forced theoretical metabolic scheme in 97%, and more than complex, tangled. 

Thereby, our discovery of the ability of the eukaryotic cell to transform the power of light into chemical energy, by dissociating water, as in plants; it forces us to modify our concepts about the functioning of the human body, through curricula and textbooks, opening a new panorama in biology and medicine.

This work was possible thanks to an unrestricted grant from Human Photosynthesis™ Research Center. C.S. Aguascalientes 20000, Mexico.

None.

1. Cockerell OC, Iino Hayes N, Sylvester R (2021) The neurological risks of playing association football. JRSM Open 12: 20542704211055558.
2. Shima S, Shikano T, Kitamura T, Masuda Y, Tsukumo T, et al. (1984) Depression and ventricular enlargement. Acta Psychiatr Scand 70: 275-277.
3. Scott ML, Golden CJ, Ruedrich SL, Bishop RJ (1983) Ventricular enlargement in major depression. Psychiatry Res 8: 91-93.
4. Pearlson GD, Veroff AE (1981) Computerised tomographic scan changes in manic-depressive illness. Lancet 2: 470.
5. Tavares TP, Mitchell DGV, Coleman K, Shoesmith C, Bartha R, et al. (2019) Ventricular volume expansion in presymptomatic genetic frontotemporal dementia. Neurology 93): 1699-1706.
6. Carmichael OT, Kuller LH, Lopez OL, Thompson PM, Dutton RA, et al. (2007) Cerebral ventricular changes associated with transitions between normal cognitive function, mild cognitive impairment, and dementia. Alzheimer Dis Assoc Disord 21: 14-24.
7. Coffey CE, Ratcliff G, Saxton JA, Bryan RN, Fried LP, et al. (2001) Cognitive correlates of human brain aging: A quantitative magnetic resonance imaging investigation. J Neuropsychiatry Clin Neurosci 13: 471-485.
8. Reiss AL, Faruque F, Naidu S, Abrams M, Beaty T, et al. (1993) Neuroanatomy of Rett syndrome: A volumetric imaging study. Ann Neurol 34: 227-234.
9. Hohman TJ, McLaren DG, Mormino EC, Gifford KA, Libon DJ, et al. (2016) Asymptomatic Alzheimer disease: Defining resilience. Neurology 87: 2443-2450.
10. Dadar M, Manera AL, Zinman L, Korngut L, Genge A, et al. (2020) Cerebral atrophy in amyotrophic lateral sclerosis parallels the pathological distribution of TDP43. Brain Commun 2: fcaa061.
11. Scarmeas N, Chin SS, Marder K (2001) Cortical basal ganglionic degeneration. Sci Aging Knowledge Environ 2001: dn1.
12. Kalkers NF, Ameziane N, Bot JC, Minneboo A, Polman CH, et al. (2002) Longitudinal Brain Volume Measurement in Multiple Sclerosis: Rate of Brain Atrophy Is Independent of the Disease Subtype. Arch Neurol 59: 1572-1576.
13. Brandt J, Bylsma FW, Gross R, Stine OC, Ranen N, et al. (1996) Trinucleotide repeat length and clinical progression in Huntington's disease. Neurology 46: 527-531.
14. Lewis MM, Smith AB, Styner M, Gu H, Poole R, et al. (2009) Asymmetrical lateral ventricular enlargement in Parkinson’s disease. Eur J Neurol 16: 475-481.
15. Conrady CD, Zheng M, van Rooijen N, Drevets DA, Royer D, et al. (2013) Microglia and a functional type I IFN pathway are required to counter HSV-1-driven brain lateral ventricle enlargement and encephalitis. J Immunol 190: 2807-2817.
16. Feng R, Wang H, Wang J, Shrom D, Zeng X, et al. (2004) Forebrain degeneration and ventricle enlargement caused by double knockout of Alzheimer's presenilin-1 and presenilin-2. Proc Natl Acad Sci USA 101: 8162-8167.
17. Van Ombergen A, Jillings S, Jeurissen B, Tomilovskaya E, Rumshiskaya A, et al. (2019) Brain ventricular volume changes induced by long-duration spaceflight. Proc Natl Acad Sci USA 116: 10531-10536.
18. Mader TH, Gibson CR, Pass AF, Kramer LA, Lee AG, et al. (2011) Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology 118: 2058-2069.
19. Laurie SS, Macias BR, Dunn JT, Young M, Stern C, et al. (2019) Optic disc edema after 30 days of strict head-down tilt bed rest. Ophthalmology 126: 467-468.
20. Lee AG, Mader TH, Gibson CR, Tarver W, Rabiei P, et al. (2020) Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: A review and an update. NPJ Microgravity 6: 7.
21. Marshall-Goebel K, Stevens B, Rao CV, Suarez JI, Calvillo E, et al. (2018) Internal jugular vein volume during head-down tilt and carbon dioxide exposure in the SPACECOT study. Aerosp Med Hum Perform 89: 351-356.
22. García-Verdugo JM, Doetsch F, Wichterle H, Lim DA, Alvarez-Buylla A (1998) Architecture and cell types of the adult subventricular zone: In search of the stem cells. J Neurobiol 36: 234-248.