Effects of prenatal photobiomodulation treatment on neonatal hypoxic ischemia in rat offspring

Abstract

Neonatal hypoxic-ischemic (HI) injury is a severe complication often leading to neonatal death and long-term neurobehavioral deficits in children. Currently, the only treatment option available for neonatal HI injury is therapeutic hypothermia. However, the necessary specialized equipment, possible adverse side effects, and limited effectiveness of this therapy creates an urgent need for the development of new HI treatment methods. Photobiomodulation (PBM) has been shown to be neuroprotective against multiple brain disorders in animal models, as well as limited human studies. However, the effects of PBM treatment on neonatal HI injury remain unclear. Methods: Two-minutes PBM (808 nm continuous wave laser, 8 mW/cm 2 on neonatal brain) was applied three times weekly on the abdomen of pregnant rats from gestation day 1 (GD1) to GD21. After neonatal right common carotid artery ligation, cortex- and hippocampus-related behavioral deficits due to HI insult were measured using a battery of behavioral tests. The effects of HI insult and PBM pretreatment on infarct size; synaptic, dendritic, and white matter damage; neuronal degeneration; apoptosis; mitochondrial function; mitochondrial fragmentation; oxidative stress; and gliosis were then assessed. Results: Prenatal PBM treatment significantly improved the survival rate of neonatal rats and decreased infarct size after HI insult. Behavioral tests revealed that prenatal PBM treatment significantly alleviated cortex-related motor deficits and hippocampus-related memory and learning dysfunction. In addition, mitochondrial function and integrity were protected in HI animals treated with PBM. Additional studies revealed that prenatal PBM treatment significantly alleviated HI-induced neuroinflammation, oxidative stress, and myeloid cell/astrocyte activation. Conclusion: Prenatal PBM treatment exerts neuroprotective effects on neonatal HI rats. Underlying mechanisms for this neuroprotection may include preservation of mitochondrial function, reduction of inflammation, and decreased oxidative stress. Our findings support the possible use of PBM treatment in high-risk pregnancies to alleviate or prevent HI-induced brain injury in the perinatal period.

Non-invasive photobiomodulation treatment in an Alzheimer Disease-like transgenic rat model

“…The Barnes maze task was performed to measure hippocampus-dependent spatial learning and memory following our previously published procedures 28 . The Barnes maze used in our study consists of a circular platform (100 cm high) with 18 holes around the circumference.…”

“…All fluorescent images were analyzed using ImageJ software (Version 1.49, NIH, Bethesda, MD, USA) or Imaris software (Bitplane AG, Zürich, Switzerland). 3D reconstruction was performed using Imaris software following the instructions described in previous studies 28 , 31 . The smoothing was set at 0.4 μm for all images and channels.…”

“…The activity of caspase 3 and caspase 9 was measured using fluorometric substrates as described in our previous studies 28 , 35 . In brief, proteins from the cortex and hippocampus were incubated with the fluorometric substrates Ac-DEVD-AMC (caspase 3 substrate) and Ac-LEHD-AMC (caspase 9 substrate) at 37 °C for 1 h. Thereafter, the mixture of the protein and the substrate was measured on Synergy HT Microplate reader (BioTek Instruments Inc, Winooski, VT, USA) with excitation at 360 nm excitation/460 nm emission.…”

“…Total antioxidant capacity assay (Cayman Chemical, Ann Arbor, MI, USA) was applied to assess the total antioxidant capacity as described in our previous studies 28 . Briefly, equal amounts of total protein from each sample were incubated with metmyoglobin (10 µL) and chromogen (150 µL) following the instruction of the vendor.…”

Therapeutic Potential of Photobiomodulation for Chronic Kidney Disease

“…PBM has been used clinically for more than 50 years and studied in various diseases and conditions, such as muscle [ 5 ], wound healing [ 6 ], pain relief [ 7 ], arthritis [ 8 ], hair loss [ 9 ], orthodontic mini-implant stability [ 10 ], neurodegenerative diseases [ 11 ] and most recently in COVID-19 patients [ 12 ]. PBM has been shown over decades to be a patient-directed, adjunctive, effective, non-invasive, and safe treatment option to mitigate mitochondrial dysfunction [ 13 ], oxidative stress [ 14 , 15 ], inflammatory conditions [ 16 ], and, more recently, gut microbiota dysbiosis [ 17 ], which are all primary contributors to CKD. Notably, several studies have demonstrated a positive effect of PBM in different models of kidney diseases, including acute kidney injury, glomerulonephritis, and metabolic syndrome-related kidney injury [ 18 ].…”