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Biomedical subjects

Uri Oron

Publications and source records attributed to Uri Oron.

13 recordsLinked to original sources

Low-level laser therapy applied transcranially to rats after induction of stroke significantly reduces long-term neurological deficits.

BACKGROUND AND PURPOSE: Low-level laser therapy (LLLT) modulates various biological processes. In the present study, we assessed the hypothesis that LLLT after induction of stroke may have a beneficial effect on ischemic brain tissue. METHODS: Two sets of experiments were performed. Stroke was induced in rats by (1) permanent occlusion of the middle cerebral artery through a craniotomy or (2) insertion of a filament. After induction of stroke, a battery of neurological and functional tests (neurological score, adhesive removal) was performed. Four and 24 hours poststroke, a Ga-As diode laser was used transcranially to illuminate the hemisphere contralateral to the stroke at a power density of 7.5 mW/cm2. RESULTS: In both models of stroke, LLLT significantly reduced neurological deficits when applied 24 hours poststroke. Application of the laser at 4 hours poststroke did not affect the neurological outcome of the stroke-induced rats as compared with controls. There was no statistically significant difference in the stroke lesion area between control and laser-irradiated rats. The number of newly formed neuronal cells, assessed by double immunoreactivity to bromodeoxyuridine and tubulin isotype III as well as migrating cells (doublecortin immunoactivity), was significantly elevated in the subventricular zone of the hemisphere ipsilateral to the induction of stroke when treated by LLLT. CONCLUSIONS: Our data suggest that a noninvasive intervention of LLLT issued 24 hours after acute stroke may provide a significant functional benefit with an underlying mechanism possibly being induction of neurogenesis.

Animals↗

Transcranial application of low-energy laser irradiation improves neurological deficits in rats following acute stroke.

BACKGROUND AND OBJECTIVES: Low-level laser therapy (LLLT) has been shown to have beneficial effects on ischemic skeletal and heart muscles tissues. The aim of the present study was to approve the effectiveness of LLLT treatment at different locations on the brain in acute stroked rats. STUDY DESIGN/MATERIALS AND METHODS: Stroke was induced in 169 rats that were divided into four groups: control non-laser and three laser-treated groups where laser was employed ipsilateral, contralateral, and both to the side of the induced stroke. Rats were tested for neurological function. RESULTS: In all three laser-treated groups, a marked and significant improvement in neurological deficits was evident at 14, 21, and 28 days post stroke relative to the non-treated group. CONCLUSIONS: These observations suggest that LLLT applied at different locations in the skull and in a rather delayed-phase post stroke effectively improves neurological function after acute stroke in rats.

Analysis of Variance↗

Modulations of VEGF and iNOS in the rat heart by low level laser therapy are associated with cardioprotection and enhanced angiogenesis.

BACKGROUND AND OBJECTIVES: It has been shown previously that low-level laser therapy (LLLT) significantly reduces infarct size following induction of myocardial infarction in rats and dogs. The aim of the present study was to investigate the effect of LLLT on the expression of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS). STUDY DESIGN AND MATERIAL AND METHODS: Myocardial infarction was induced by occlusion of the left descending artery in 87 rats. LLLT was applied to intact and post-infarction. VEGF, iNOS, and angiogenesis were determined. RESULTS: Both the laser-irradiated rat hearts post-infarction and intact hearts demonstrated a significant increase in VEGF and iNOS expression compared to non-laser-irradiated hearts. LLLT also caused a significant elevation in angiogenesis. CONCLUSIONS: It is concluded that VEGF and iNOS expression in the infarcted rat heart is markedly upregulated by LLLT and is associated with enhanced angiogenesis and cardioprotection.

Animals↗

Photoengineering of tissue repair in skeletal and cardiac muscles.

This review discusses the application of He-Ne laser irradiation to injured muscles at optimal power densities and optimal timing, which was found to significantly enhance (twofold) muscle regeneration in rats and, even more, in the cold-blooded toads. Multiple and frequent (daily) application of the laser in the toad model was found to be less effective than irradiation on alternate days. It was found that in the ischemia/reperfusion type of injury in the skeletal leg muscles (3 h of ischemia), infrared Ga-Al-As laser irradiation reduced muscle degeneration, increased the cytoprotective heat shock proteins (HSP-70i) content, and produced a twofold increase in total antioxidants. In vitro studies on myogenic satellite cells (SC) revealed that phototherapy restored their proliferation. Phototherapy induced mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) phosphorylation in these cells, probably by specific receptor phosphorylation. Cell cycle entry and the accumulation of satellite cells around isolated single myofibers cultured in vitro was also stimulated by phototherapy. Phototherapy also had beneficial effects on mouse, rat, dog and pig ischemic heart models. In these models, it was found that phototherapy markedly and significantly reduced (50-70%) the scar tissue formed after induction of myocardial infarction (MI). The phototherapeutic effect was associated with reduction of ventricular dilatation, preservation of mitochondria and elevation of HSP- 70i and ATP in the infarcted zone. It is concluded that phototherapy using the correct parameters and timing has a markedly beneficial effect on repair processes after injury or ischemia in skeletal and heart muscles. This phenomenon may have clinical applications.

Animals↗

Effects of power densities, continuous and pulse frequencies, and number of sessions of low-level laser therapy on intact rat brain.

OBJECTIVE: The aim of the present study was to investigate the possible short- and long-term adverse neurological effects of low-level laser therapy (LLLT) given at different power densities, frequencies, and modalities on the intact rat brain. BACKGROUND DATA: LLLT has been shown to modulate biological processes depending on power density, wavelength, and frequency. To date, few well-controlled safety studies on LLLT are available. METHODS: One hundred and eighteen rats were used in the study. Diode laser (808 nm, wavelength) was used to deliver power densities of 7.5, 75, and 750 mW/cm2 transcranially to the brain cortex of mature rats, in either continuous wave (CW) or pulse (Pu) modes. Multiple doses of 7.5 mW/cm2 were also applied. Standard neurological examination of the rats was performed during the follow-up periods after laser irradiation. Histology was performed at light and electron microscopy levels. RESULTS: Both the scores from standard neurological tests and the histopathological examination indicated that there was no long-term difference between laser-treated and control groups up to 70 days post-treatment. The only rats showing an adverse neurological effect were those in the 750 mW/cm2 (about 100-fold optimal dose), CW mode group. In Pu mode, there was much less heating, and no tissue damage was noted. CONCLUSION: Long-term safety tests lasting 30 and 70 days at optimal 10x and 100x doses, as well as at multiple doses at the same power densities, indicate that the tested laser energy doses are safe under this treatment regime. Neurological deficits and histopathological damage to 750 mW/cm2 CW laser irradiation are attributed to thermal damage and not due to tissue-photon interactions.

Animals↗

Protection of skeletal muscles from ischemic injury: low-level laser therapy increases antioxidant activity.

OBJECTIVE: The aim of this study was to investigate the effect of low-level laser therapy (LLLT) on ischemic-reperfusion (I-R) injury in the gastrocnemius muscle of the rat. BACKGROUND DATA: Ischemic injury in skeletal muscle is initiated during hypoxia and is aggravated by reoxygenation during blood reperfusion and accumulation of cytotoxic reactive oxygen superoxides. LLLT has been found to biostimulate various biological processes, such as attenuation of ischemic injury in the heart. MATERIALS AND METHODS: The injury was induced in the gastrocnemius muscles of 106 rats by complete occlusion of the blood supply for 3 h, followed by reperfusion. Another group of intact rats served to investigate the effect of LLLT on intact nonischemic muscles. Creatine phosphokinase, acid phosphatase, and heat shock protein were determined 7 days after I-R injury and antioxidant levels 2 h after reperfusion. RESULTS: Laser irradiation (Ga-As, 810 nm) was applied to the muscles immediately and 1 h following blood supply occlusion. It was found that laser irradiation markedly protects skeletal muscles from degeneration following acute I-R injury. This was evident by significantly (p < 0.05) higher content of creatine phosphokinase activity and lower (p < 0.05) activity of acid phosphatase in the LLLT-treated muscles relative to the injured non-irradiated ones. The content of antioxidants and heat shock proteins was also higher (p < 0.05) in the LLLT-treated muscles relative to that of injured non-irradiated muscles. CONCLUSION: The present study describes for the first time the ability of LLLT to significantly prevent degeneration following ischemia/reperfusion injury in skeletal muscles, probably by induction of synthesis of antioxidants and other cytoprotective proteins, such as hsp-70i. The elevation of antioxidants was also evident in intact muscle following LLLT. The above phenomenon may also be of clinical relevance in scheduled surgery or microsurgery requiring extended tourniquet applications to skeletal muscle followed by reperfusion.

Animals↗

Low-energy laser irradiation enhances de novo protein synthesis via its effects on translation-regulatory proteins in skeletal muscle myoblasts.

Low-energy laser irradiation (LELI) drives quiescent skeletal muscle satellite cells into the cell cycle and enhances their proliferation, thereby promoting skeletal muscle regeneration. Ongoing protein synthesis is a prerequisite for these processes. Here, we studied the signaling pathways involved in the LELI regulation of protein synthesis. High levels of labeled [35S]methionine incorporation were detected in LELI cells as early as 20 min after irradiation, suggesting translation of pre-existing mRNAs. Induced levels of protein synthesis were detected up until 8 h after LELI implying a role for LELI in de novo protein synthesis. Elevated levels of cyclin D1, associated with augmented phosphorylation of the eukaryotic initiation factor 4E (eIF4E) and its inhibitory binding protein PHAS-I, suggested the involvement of LELI in the initiation steps of protein translation. In the presence of the MEK inhibitor, PD98059, eIF4E phosphorylation was abolished and levels of cyclin D1 were dramatically reduced. The LELI-induced PHAS-I phosphorylation was abolished after preincubation with the PI3K inhibitor, Wortmannin. Concomitantly, LELI enhanced Akt phosphorylation, which was attenuated in the presence of Wortmannin. Taken together, these results suggest that LELI induces protein translation via the PI3K/Akt and Ras/Raf/ERK pathways.

Adaptor Proteins, Signal Transducing↗

A preliminary investigation into light-modulated replication of nanobacteria and heart disease.

OBJECTIVE: The purpose of this preliminary study is to evaluate the effect of various wavelengths of light on nanobacteria (NB). BACKGROUND DATA: NB and mitochondria use light for biological processes. NB have been described as multifunctional primordial nanovesicles with the potential to utilize solar energy for replication. NB produce slime, a process common to living bacteria. Slime release is an evolutionary important stress-dependent phenomenon increasing the survival chance of individual bacteria in a colony. In the cardiovascular system, stress-induced bacterial colony formation may lead to a deposition of plaque. METHODS: Cultured NB were irradiated with NASA-LEDs at different wavelengths of light: 670, 728 and 880 nm. Light intensities were about 500k Wm(-2), and energy density was 1 x 10(4) J m(-2). RESULTS: Monochromatic light clearly affected replication of NB. Maximum replication was achieved at 670 nm. CONCLUSIONS: The results indicate that suitable wavelengths of light could be instrumental in elevating the vitality level of NB, preventing the production of NB-mediated slime, and simultaneously increasing the vitality level of mitochondria. The finding could stimulate the design of cooperative therapy concepts that could reduce death caused by myocardial infarcts.

Bacteria↗

Low-energy laser irradiation promotes the survival and cell cycle entry of skeletal muscle satellite cells.

Low energy laser irradiation (LELI) has been shown to promote skeletal muscle cell activation and proliferation in primary cultures of satellite cells as well as in myogenic cell lines. Here, we have extended these studies to isolated myofibers. These constitute the minimum viable functional unit of the skeletal muscle, thus providing a close model of in vivo regeneration of muscle tissue. We show that LELI stimulates cell cycle entry and the accumulation of satellite cells around isolated single fibers grown under serum-free conditions and that these effects act synergistically with the addition of serum. Moreover, for the first time we show that LELI promotes the survival of fibers and their adjacent cells, as well as cultured myogenic cells, under serum-free conditions that normally lead to apoptosis. In both systems, expression of the anti-apoptotic protein Bcl-2 was markedly increased, whereas expression of the pro-apoptotic protein BAX was reduced. In culture, these changes were accompanied by a reduction in the expression of p53 and the cyclin-dependent kinase inhibitor p21, reflecting the small decrease in viable cells 24 hours after irradiation. These findings implicate regulation of these factors as part of the protective role of LELI against apoptosis. Taken together, our findings are of critical importance in attempts to improve muscle regeneration following injury.

Animals↗

Technical delivery of myogenic cells through an endocardial injection catheter for myocardial cell implantation.

BACKGROUND: The next clinical frontier in the therapeutics of ischemic heart disease may involve the development and delivery of specific molecules and cells into the myocardium. The aim of the present study was to evaluate the efficiency and safety of the MyoStar injection catheter (Biosense-Webster Inc.) that has recently been developed to deliver molecules and cells to the myocardium. The 8 Fr (110 cm length) catheter comprises a navigation sensor with a 27 gauge needle at the distal tip. METHODS: Mouse myogenic cells (C2) were delivered to a tissue culture dish through different modalities: a standard laboratory pipette, a syringe needle (27 gauge) and the injection catheter. The cells were counted and monitored for growth and differentiation in the tissue culture immediately after delivery and two, three and six days later. Cells that were injected through a regular syringe needle or through the injection catheter demonstrated the same capacity to proliferate in tissue culture up to six days. RESULTS: The behavior of the cells in culture (fusion) was identical for the cells delivered to the tissue culture by a pipette or by the injection catheter. CONCLUSION: The results of the present study indicate that delivery of cells through the MyoStar injection catheter is a method with no significant loss or adverse effects to the cells along the path of the catheter. The catheter, which possesses both injection and navigation capabilities, can be used to deliver cell therapy to patients with ischemic heart disease.

Journal Article↗

Living nanovesicles--chemical and physical survival strategies of primordial biosystems.

Life on Earth and Mars could have started with self-assembled nanovesicles similar to the present nanobacteria (NB). To resist extreme environmental stress situations and periods of nutritional deprivation, nanovesicles would have had a chemical composition protected by a closed mineralized compartment, facilitating their development in a primordial soup, or other early wet environment. Their survivability would have been enhanced if they had mechanisms for metabolic communication, and an ability to collect primordially available energy forms. Here, we establish an irreducible model system for life formation starting with NB.

Apatites↗