VEA: OZONOTERAPIA
FUNDAMENTOS E INVESTIGACIONES
EQUIPOS Y DERIVADOS

OZONE THERAPY IN THE FUNCTIONAL RECOVERY FROM DISEASES INVOLVING DAMAGE TO CENTRAL NERVOUS SYSTEM CELLS.

PhD. GOMEZ MORALEDA, M.A.

PAPER PRESENTED AT THE 12th WORLD CONGRESS OF THE INTERNATIONAL OZONE ASSOCIATION
MAY/95, LILLE, FRANCE 

Abstract

On the basis of personal experience in preclinical and clinical experiments, sets of results are presented, concerning the Ozone Therapy treatment of different groups of subjects suffering from various diseases which involve degenerative or ischemic damage of central nervous system cells (Senile Dementia, Cerebro Vascular Ischemia, Hipoacusia, Optic Nerve Dysfunctions, Sequels of Glaucoma, Retinitis Pigmentosa and Maculopathies).

Regarding previously mentioned results, some interrelated hypothesis are formulated to explain the different effects achieved in functional recovery of patients with the Ozone Therapy. These are based in some of the already known effects of ozone on living cells, so as in the cells physiology of those subsystems of the central nervous system involved in each disease.

 

INTRODUCTION

Ozone has been widely applied in many diseases caused by peripheric circulatory disturbances, infections, alterations of the immune system, esthetics, etc., but less attention has been paid to research about nervous cells damage produced by degenerative and ischemic diseases affecting subsystems of the central nervous system (CNS), so as by other causes as traumatic or compressive events, etc.

Several studies were performed in Cuba, under the scientific direction of the author in the National Center for Scientific Research, Ozone Research Center and in various Hospitals and Health Institutes, concerning different diseases with their common basis on Central Nervous System dysfunctions.

Present paper shows a brief summary of these diseases, some of their main characteristics, and the most important positive results achieved after the ozone therapy treatments of groups of patients suffering from them. A set of hypothesis is also proposed to explain such results.

MAIN TEXT

DISEASES:

The histopathology of this disease (Marquez 1962, Daugman, 1986 and Scuderi & Moreno, 1986) show vascular alterations due to retinal vessels attenuation. Also choroidal sclerosis was reported, which contributes to tissue anoxia and leads to atrophy of retina layers. Nevertheless, drugs with oxygenating action on the CNS tissues and the retina, used so far, did not give satisfactory response to treatments. Other theories (Wirt, 1984, DukeElder, 1984 and Vodovozov, 1986) invoked encephalon disturbs, immunological alterations, lack of vitamins, etc. Nevertheless, therapeutics directed to these causes did not give the expected results as well.

Today, neuroplasticity is recognized as a nervous tissue property in spite of neurons incapacity for multiplication (BachRita, 1980, Estrada, 1988 Boisson, 1990). Peripheral nervous system possibilities of regeneration is well known and recent research emphasized this property, though in lower degree, in the CNS (Varon et al.,1986, Aguayo et al.,1986, Aguayo et al.,1985).

Optic nerve (ON) as a part of the CNS is deprived of myelin sheath and has been the target of some experimental work on neuroplasticity. Aguayo et al., in 1986 showed the ON axons possibilities of regeneration in rats when they are able to make appropriate contact with the coliculli cells, through peripheral nerve segment grafts.

Neurotransplantology is gaining ground at present, but investigations on the ON injuries are still in animal experimental stage (1989, Carmignoto et al., 1989, Sievers & Hausmann, 1989) and no conclusive results have been reported in man. In the process of the OND not all nerve fibers are fully degenerated and this depends on the intensity of the injury, time of evolution, glial reactions, etc. Such criteria are taken into consideration to try to develope different therapeutical methods, including hyperbaric oxygenation and photic and electric stimulation, with poor effect up to date.

The characteristic pathologic rise in intra ocular tension, joined to the circulatory deficiency and the metabolic changes in retina and ON deteriorate the nervous function, leading to the glaucomatous optic atrophy. Changes in circulation cause the variation of the blood rheological properties, hypoxia and modifications in the oxygen metabolism, which in sum deprive the metabolism and produce alterations in ocular tissue trophism (Kashintseva & Kribonski, 1979, Mukha, 1990).

Experimental models of glaucoma show destructive damage in ocular vessels and tissue, mainly in the draining system, provoking not only ocular tension alterations, but also altered metabolic processes (Conde & Gurtobaya, 1977, Nesterov, 1982).

Some years ago, in addition to the local hypotensors, pharmacologic complexes were attempted to improve haemodinamics and restore the normal oxidation processes in ocular tissue, with the aim of to stimulate the deteriorated nervous function (Conde, 1977). They exhibited poor evidence of improvement and no long lasting effects.

Classification scale of senile dementias recognized as "incurable", published by Hachinsky and in agreement with other authors (Smith & Kiloh, 1981) was applied, where Alzheimer dementia constituted approximately 60 % of cases, those of vascular nature represented 20 % and mixed types (vascular - degenerative), the remaining 20 %. It allowed to study "incurable" dementias, excluding all those cases potentially reversible and different in nature, which in elderly patients can be expressed as pseudo demential state.

In geriatrics, the concept of health is defined in terms of function, a healthy elderly is not that one, who does not suffer from any pathology, but one who is autonomous. The fundamental objective for incurable SD treatments (of vascular or degenerative ethiology) is to increase the autonomy of elderly, especially in regards to mental condition, self medication capacity and daily life activities performance, giving special attention to multidimensional evaluation and validity.

Lot of drugs have been tested throughout the time for therapeutics in this disease, from psycho pharmacs to neural metabolic activators, including, of course, cerebral vasodilators. Many authors (Pfeiffer, 1980, Greenblatt et al., 1975, Jenike, 1987, Kane & Smith, 1982, Jenike, 1988) accept that adverse reactions produced with the use of these medications must be constantly considered, specially because no really positive effects have been found.

In ischemic cerebro vascular disease, reduction in the oxygenation pattern of brain takes place. Consequently, normal nutritional cycle of neurons is reversed and anaerobic glycolisis prevails, producing drop in available ATP for the energetic cycle of neurons (Heiss, 1983, Heiss et al., 1983). Several treatments apply for this disease. Some of them try to avoid the appearance of phenomenon (Devesa, 1992), while others try to diminish mortality and sequels in those who already present symptoms. In both groups, some progress has been achieved, specially in the first group, by means of appropriate handling of preventive aspects. Results in the second group are not so promising, specially concerning sequels.

Ages (Ages, 1989) reports certain metabolic alterations to occur in internal ear as cocleo vestibular manifestations of hypothyroidism, so as in the vertigo syndrome of cervical origin, exhibiting positive response to cinarizine (Bartual, 1988). Noise induced auditive dysfunction causes lowering of oxygen tension, as in the Manasse otosclerosis, with consequent hypoxia in the membranous labyrinth and accumulation of toxic metabolic detritus, damaging it. Presbiacusia involves depletion of cellular population, due to extra cellular deposition of material and accumulation of toxic substances in the cells.

 

 

EXPERIMENTAL RESULTS

Most important positive results achieved by ozone therapy in the clinical trials performed (Menendez et. al., 1990, Menendez et. al., 1992, Santiesteban et. al., 1993, Ferrer et. al., 1992, Devesa et. al., 1993, Rodriguez et. al., 1993, Basabe et. al., 1992), are as follows:

TABLE I

RETINITIS PIGMENTOSA

ENLARGEMENT OF PATIENTS VISUAL FIELDS

WAYS OF ADMINISTRATION

NUMBER OF PATIENTS

OUTSTANDING ENLARGEMENT

SLIGHT ENLARGEMENT

NO EFFECT

AUTOHEMOTHERAPY

217

144

45

28

INTRAMUSCULAR

25

12

9

4

TOTAL

242

156

54

32

%

100

64,5

22,3

13,2

* Outstanding enlargement means grater than 5 degrees
** Slight enlargement means up to 5 degrees.

TABLE II

OPTIC NERVE DISFUNCTION

PARAMETER

IMPROVEMENT %

PRCST (> 1 Triad)

85.7

Visual Field (> 10 Degrees)

82.7

Visual Acuity (> 0.1 deg. Snellen)

54.5

Visual Evoked Potential

37.0*

PRCST – Pelli Robson Contrast Sensitivity Test
N = 67 Eyes
* Amplitude increment > 1uv. or P100 Wave Latency shortening > 4 ms.

TABLE III

PRIMARY OPEN ANGLE GLAUCOMA

PARAMETER

IMPROVEMENT %

Visual Field

76.0

Visual Acuity

71.5

Intra Ocular Tension

18.4

N = 196 Eyes

TABLE IV

SENIL DEMENTIA (DOUBLE BLIND STUDY)

GROUP

PATIENTS NUMBER

MENTAL CONDITION

SELF MEDICATION CAPACITY

DAILY LIFE ACTIVITIES

OZONE

30

25 (83%)

25 (83%)

27 (90%)

OXYGEN

30

--

--

--

 

TABLE V

ISCHEMIC CEREBRO VASCULAR DISEASE

IMPROVEMENT AFTER TREATMENT

GROUP

PATIENTS NUMBER

MENTAL CONDITION

SELF MEDICATION CAPACITY

DAILY LIFE ACTIVITIES

ACUTE

48

48 (100%)

48 (100%)

48 (100%)

ANCIENT

42

38 (90.5%)

36 (85.7%)

40 (95.2%)

CHRONIC

30

20 (66.6%)

18 (60.0%)

24 (80.0%)

ACUTE - Admited to study with less of 30 days after the occurrence.
ANCIENT - Admited to study with 1 to 6 months after the occurrence.
CHRONIC - Admited to study with 7 to 12 months after the occurrence.

 

TABLE VI

COCHLEO VESTIBULAR SYNDROME

IMPROVEMENT IN AIRWAY AUDIOMETRIES AFTER TREATMENT

FREQUENCIES

IMPROVED
(%)

NO EFFECT
(%)

WORSE
(%)

TOTAL EARS

GENERAL MEAN
(250-8000 Hz)
17 (50.0) 16 (47.0) 1 (3.0) 34
CONVERSATION MEAN
(500-2000 Hz)
19 (56.0) 14 (41.0) 1 (3.0) 34
HIGH MEAN
(2000-8000 Hz)
17 (50.0) 15 (44.0) 2 (6.0) 34

Improved corresponds to a gain greater than 5 dB.
Worse corresponds to a loss greater then 5 dB.

 

DISCUSSION

Ozone presents important properties which make it very useful in medical field, related to its stimulating effect on oxygen metabolic processes and blood circulation, where it modifies the rheologic properties of the blood, preventing erythrocytes from aggregation and increasing their deformability and permeability. To understand the ozone action mechanism it is important to consider not only its possible direct effect as an oxygenating agent, but also a complex of biochemical processes. It is known that ozone selectively reacts with the unsaturated fatty acids of the phospholipidic layer of cell membranes, producing a series of short chain peroxides "ozone metabolites" with important functions in the organism.

These include increasing of the oxygen absorption capacity of erythrocytes as well as its transference to tissue, stimulation of oxygen metabolization through the reactivation of several biochemical cycles, activation of enzymatic redox systems which protect against degenerative processes, and modulating effect on biological and immune responses. At a first glance, the mechanisms which could explain the satisfactory improvements in the majority of patients under the different clinical trials presented, all of them involving damage to CNS cells, are neuroplasticity and CNS cells revitalization. It is already demonstrated in previous reports the ability of ozone to enhance blood flow and oxygen supply to tissue, and that could be a part of the effects on the diseases discussed, but not enough to explain the observed degree of stimulation of those CNS cells processes mentioned above, taking into account that other drugs with similar oxygenating effects were applied to the same diseases with no such positive results.

In the past few years, it has been recognized that in some diseases affecting CNS cells, at least part of the damaged and dysfunctional ones could be still alive in some kind of sub functional state during some time. This opens the possibility to find a way to reactivate them and restore their functions. Also neuroplasticity, makes possible the substitution of the already died cells functions by other neighboring cells, which in turn should improve their capabilities.

Stimulation of glycolisis by ozone metabolites could be one of the keys to understand the functional recovery of those cells severely damaged but still not completely died. These cells, as a result of hypoxic conditions due to different causes (ischemia, compression, toxicity, trauma, edema, expression of inherited dysfunctions, degenerative processes, etc.), could have been forced to change their metabolism from the normal aerobic, to anaerobic. It is very well known that anaerobic glycolisis yield many times less energy than the aerobic, and probably the cells forced to that condition, lack of ATP, would slowly die. In those cells not having the ability to spontaneously change their metabolism to aerobic again, subsequent increases of oxygen availability would not be enough to restore normal metabolic pathways, specially aerobic glycolisis, and the cells, would continue suffering deterioration, not having energy enough for their vital functions.

Ozone metabolites, being able to stimulate aerobic glycolisis in the cells by means of activation of the enzymes involved, and improving the availability of energy as ATP, would be the trigger for both: revitalization with functional recovery of those deprived, but still alive cells, and also neuroplasticity, it means assumption (partially at least) of the functions of those already died by adjacent healthy and activated neighboring cells. These hypotheses agree with the observed fact that ozone therapy was more effective in such diseases, the earlier the treatment was applied, being this parameter quantitatively related to the survivance of dysfunctional cells. Not less important is that similar success was achieved in diseases of different etiology, as is the case for Alzheimer disease and vascular dementia, ON dysfunctions (except for Optic Leber Atrophy, in which no improvement was observed) and CVS.

Lack or poor improvement in those patients who were completely blind or deaf, or presented signs of deep or complete atrophy, could suggest that good results in the application of the ozone therapy could be expected when some degree of the functions remain and atrophy is not complete. In other words, it seems probable that structural substratum and or functional reserves are necessary, so that the neuroplasticity or functional recovery mechanisms could be activated. This idea would be supported also by the fact that recovery was faster and more evident in the less severe or recent cases.

The mechanism of ozone actions in some of these entities could also be related to its ability to significantly stimulate other enzymatic processes in cells, some of them vital for cell protection against degenerative processes, such as metabolization of aggressive oxygen species and detoxification. Examples could be degenerative processes in which detritus of cells are accumulated, so aggravating the damage to other cells. In such cases, some specialized cells of the immune systems should also perform their specific cleaning function, such as macrofages. Some reports about ozone stimulation or modulation of macrofages, linfocites, etc point out the dose dependent effect of ozone on the immune system, and establish the marked stimulation which can be achieved with the appropriate dose of ozone in the phagocitosis of macrofages.

Regarding RP, for example, it was reported that the cells of the pigmented epithelium, adjacent to the photoreceptors layer, have the responsibility for phagocitosis of the segments of photoreceptors that are periodically rejected from them when already exhausted. One of the mechanisms proposed to explain the degeneration of photoreceptors is that the pigmented epithelium cells in certain extent loss their phagocityc capacity and rejected segments are accumulated and decomposed, damaging the photoreceptors themselves by toxemia. In such process, one of the beneficial effects of ozone could be the stimulation of the phagocityc capacity of pigmented epithelium cells to eliminate toxemia and recover the functionality of photoreceptors. Similar mechanisms could also take place in the cochlear organ, were similar damage due to toxemia was already mentioned in the introduction.

 

CONCLUSIONS

In our opinion, the ozone treatment, at least, favors certain reversion of unfavorable conditions of vascular or metabolic nature in those neurons which are not completely damaged and/or in some specific adjacent cells which must protect them and so they could potentially recover their functions, at least partially.

VEA: OZONOTERAPIA
FUNDAMENTOS E INVESTIGACIONES
EQUIPOS Y DERIVADOS

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