Effects of photobiomodulation in experimental spinal cord injury models: A systematic review.

This systematic review investigated the repercussions of photobiomodulation using low-level laser therapy (LLLT) for the treatment of spinal cord injury (SCI) in experimental models. Studies were identified from relevant databases published between January 2009 and December 2021. Nineteen original articles were selected and 68.4% used light at an infrared wavelength. There was a considerable variation of the power used (from 25 to 200 mW), total application time (8-3000 s) and total energy (0.3-450 J). In 79% of the studies, irradiation was initiated immediately after or within 2 h of the SCI, and treatment time ranged continuously from 5 to 21 days. In conclusion, LLLT can be an auxiliary therapy in the treatment of SCI, playing a neuroprotective role, enabling functional recovery, increasing the concentration of nerve connections around the injury site and reducing pro-inflammatory cytokines. However, there is a need for standardization in the dosimetric parameters.

Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats.

BACKGROUND: Neurotoxic microglia and astrocytes begin to activate and participate in pathological processes after spinal cord injury (SCI), subsequently causing severe secondary damage and affecting tissue repair. We have previously reported that photobiomodulation (PBM) can promote functional recovery by reducing neuroinflammation after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM ameliorates neuroinflammation by modulating the activation of microglia and astrocytes after SCI. METHODS: Male Sprague-Dawley rats were randomly divided into three groups: a sham control group, an SCI + vehicle group and an SCI + PBM group. PBM was performed for two consecutive weeks after clip-compression SCI models were established. The activation of neurotoxic microglia and astrocytes, the level of tissue apoptosis, the number of motor neurons and the recovery of motor function were evaluated at different days post-injury (1, 3, 7, 14, and 28 days post-injury, dpi). Lipocalin 2 (Lcn2) and Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) signaling were regarded as potential targets by which PBM affected neurotoxic microglia and astrocytes. In in vitro experiments, primary microglia and astrocytes were irradiated with PBM and cotreated with cucurbitacin I (a JAK2-STAT3 pathway inhibitor), an adenovirus (shRNA-Lcn2) and recombinant Lcn2 protein. RESULTS: PBM promoted the recovery of motor function, inhibited the activation of neurotoxic microglia and astrocytes, alleviated neuroinflammation and tissue apoptosis, and increased the number of neurons retained after SCI. The upregulation of Lcn2 and the activation of the JAK2-STAT3 pathway after SCI were suppressed by PBM. In vitro experiments also showed that Lcn2 and JAK2-STAT3 were mutually promoted and that PBM interfered with this interaction, inhibiting the activation of microglia and astrocytes. CONCLUSION: Lcn2/JAK2-STAT3 crosstalk is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be suppressed by PBM.

Effects of photobiomodulation combined with MSCs transplantation on the repair of spinal cord injury in rat.

Stem cell transplantation has shown promising regenerative effects against neural injury, and photobiomodulation (PBM) can aid tissue recovery. This study aims to evaluate the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) and laser alone or combined on spinal cord injury (SCI). The animals were divided into SCI, hUCMSCs, laser treatment (LASER) and combination treatment (hUCMSCs + LASER) groups. Cell-enriched grafts of hUCMSCs (1 × 106 cells/ml) were injected at the site of antecedent trauma in SCI model rats. A 2 cm2 damaged area was irradiated with 630 nm laser at 100 mW/cm2 power for 20 min. Locomotion was evaluated using Basso-Beattie-Bresnahan (BBB) scores, and neurofilament repair were monitored by histological staining and diffusion tensor imaging (DTI). First, after SCI, the motor function of each group was restored with different degrees, the combination treatment significantly increased the BBB scores compared to either monotherapy. In addition, Nissl bodies were more numerous, and the nerve fibers were longer and thicker in the combination treatment group. Consistent with this, the in situ expression of NF-200 and glial fibrillary acidic protein in the damaged area was the highest in the combination treatment group. Finally, DTI showed that the combination therapy optimally improved neurofilament structure and arrangement. These results may show that the combination of PBM and hUCMSCs transplantation is a feasible strategy for reducing secondary damage and promoting functional recovery following SCI.

Visual outcomes of proton beam therapy for choroidal melanoma at a single institute in the Republic of Korea.

We evaluate the ocular effects of proton beam therapy (PBT) in a single institution, in Korea, and identify factors contributing to decreasing visual acuity (VA) after PBT. A total of 40 patients who received PBT for choroidal melanoma (2009‒2016) were reviewed. Dose fractionation was 60‒70 cobalt gray equivalents (CGEs) over five fractions. Complete ophthalmic examinations including funduscopy and ultrasonography were performed at baseline and at 3, 6, and 12 months after PBT, then annually thereafter. Only patients with at least 12 months follow-up were included. During the follow-up, consecutive best-corrected visual acuity (BCVA) changes were determined, and univariate and multivariate logistic regression analyses were performed to identify predictors for VA loss. The median follow-up duration was 32 months (range: 12‒82 months). The final BCVA of nine patients was > 20/40. The main cause of vision loss was intraocular bleeding, such as neovascular glaucoma or retinal hemorrhage. Vision loss was correlated with the tumor size, tumor distance to the optic disc or fovea, maculae receiving 30 CGEs, optic discs receiving 30 CGEs, and retinas receiving 30 CGEs. Approximately one-third of PBT-treated choroidal melanoma patients with good pretreatment BCVA maintained their VA. The patients who finally lost vision (VA < count fingers) usually experienced rapid declines in VA from 6‒12 months after PBT. Tumor size, tumor distance to the optic disc or fovea, volume of the macula, and optic discs or retinas receiving 30 CGEs affected the final VA.

Epidural Stimulation Combined with Triple Gene Therapy for Spinal Cord Injury Treatment.

The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals. In treated pigs, motor performance was enabled by EES and the corresponding morpho-functional changes in hind limb skeletal muscles were accompanied by the reorganization of the glial cell, the reaction of stress cell, and synaptic proteins. Our data demonstrate effects of combined EES-facilitated motor training and cell-mediated triple gene therapy after spinal contusion in large animals, informing a background for further animal studies and clinical translation.

Sensory and motor responses after photobiomodulation associated with physiotherapy in patients with incomplete spinal cord injury: clinical, randomized trial.

Complete or incomplete spinal cord injury (SCI) results in permanent neurological deficits due to the interruption of nerve impulses, causing the loss of motor and sensory function, which leads to a reduction in quality of life. The focus of rehabilitation for such individuals is to improve quality of life and promote functional recovery. Photobiomodulation (PBM) has proved to be promising complementary treatment in cases of SCI. The aim of the present study was to investigate the effects of PBM combined with physiotherapy on sensory-motor responses below the level of the injury and quality of life in individuals with SCI. Thirty participants were randomized for allocation to the PBM group (active PBM + physiotherapy) or sham group (sham PBM + physiotherapy). Physiotherapy was administered three times a week. Sensitivity and motor skills were evaluated using the ASIA impairment scale. Quality of life was assessed using the WHOQOL-BREF questionnaire. The data were analyzed with the level of significance set to 5%. Improvements in sensitivity and an increase in the perception of muscle contraction were found in the active PBM group 30 days after treatment compared with the sham group. The results of the WHOQOL-BREF questionnaire revealed a significant difference in general quality of life favoring the active PBM group over the sham group after treatment. Physiotherapy combined with PBM leads to better sensory-motor recovery in patients with SCI as well as a better perception of health and quality of life. Trial registration identifier: NCT03031223.

Recovery of Renal Function Under PSMA Mediated Radioligand Therapy of Advanced Metastasized Castration Resistant Prostate Cancer.

Radioligand therapy targeting prostate specific membrane antigen (PSMA-RLT) is becoming increasingly important in palliative care of metastasized castration resistant prostate cancer (mCRPC) as a highly effective and low toxicity therapy option. In addition to its overexpression in prostate cancer cells, PSMA is also physiologically expressed in the kidneys which is raising concerns over dose related nephrotoxicity of PSMA-RLT. We describe potential positive short-term effects of PSMA-RLT on renal function with marked recovery of a pretreatment compromised kidney.

Low-Field Magnetic Stimulation Restores Cognitive and Motor Functions in the Mouse Model of Repeated Traumatic Brain Injury: Role of Cellular Prion Protein.

Traumatic brain injury (TBI)/concussion is a growing epidemic throughout the world. Memory and neurobehavioral dysfunctions are among the sequelae of TBI. Dislodgement of cellular prion protein (PrPc) and disruption of circadian rhythm have been linked to TBI. Low-field magnetic stimulation (LFMS) is a new noninvasive repetitive transcranial magnetic stimulation (rTMS) technique that generates diffused and low-intensity magnetic stimulation to deep cortical and subcortical areas. The role of LFMS on PrPc, proteins related to the circadian rhythm, and behavior alterations in a repeated TBI mouse model were studied in the present study. TBI was induced to the mice (right hemisphere) using weight-drop method, once daily for 3 days. LFMS treatment was given for 20 min once daily for 4 days (immediately after each TBI induction). The results showed that LFMS-treated TBI mice significantly improved cognitive and motor function as evidenced by open field exploration, rotarod, and novel location recognition tasks. In addition, a significant increase in PrPc and decreased glial fibrillary acidic protein levels were observed in cortical and hippocampal regions of LFMS-treated TBI mice brain compared with sham-treated TBI mice, while neuronal nuclei level was significantly increased in cortical region. In LFMS-treated mice, a decrease in proteins related to circadian rhythm were observed, compared with sham-treated TBI mice. The results obtained from the study demonstrated the neuroprotective effect of LFMS, which may be through regulating PrPc and/or proteins related to circadian rhythm. Thus, the present study suggests that LFMS may improve the subject's neurological condition following TBI.

Neurocognitive, academic and functional outcomes in survivors of infant ependymoma (UKCCSG CNS 9204).

PURPOSE: This is the first UK multi-centre case-controlled study with follow-up in excess of 10 years to report the neurocognitive, academic and psychological outcomes of individuals diagnosed with a brain tumour in early childhood. Children enrolled into the UKCCSG CNS 9204 trial, diagnosed with intracranial ependymoma when aged ≤ 36 months old, who received a primary chemotherapy strategy to defer or avoid radiotherapy, were recruited. METHODS: Outcomes of those who relapsed and subsequently received radiotherapy (n = 13) were compared to those enrolled who did not relapse (n = 16), age-matched controls-diagnosed with solid non-central nervous system (SN-CNS; n = 15) tumours or low-grade posterior fossa pilocytic astrocytoma (PFPA; n = 15), and normative data. Analyses compared nine neurocognitive outcomes as primary measures with quality of survival as secondary measures. RESULTS: Relapsed ependymoma participants performed significantly worse than their non-relapsed counterparts on measures of Full Scale IQ, Perceptual Reasoning, Word Reading and Numerical Operations. The relapsed ependymoma group performed significantly worse than SN-CNS controls on all primary measures, whereas non-relapsing participants only differed significantly from SN-CNS controls on measures of Processing Speed and General Memory. Relapsed ependymoma participants fared worse than all groups on measures of quality of survival. CONCLUSIONS: The relapsed irradiated ependymoma group demonstrated the most significantly impaired neurocognitive outcomes at long-term follow-up. Non-relapsing participants demonstrated better outcomes than those who relapsed. Results tentatively suggest avoiding radiotherapy helped preserve neurocognitive and learning outcomes of individuals diagnosed with ependymoma when aged ≤ 36 months old. Prospective neurocognitive surveillance is required. Recommendations for clinical and research practice are provided.

The Effect of Electromagnetic Fields on Post-Operative Pain and Locomotor Recovery in Dogs with Acute, Severe Thoracolumbar Intervertebral Disc Extrusion: A Randomized Placebo-Controlled, Prospective Clinical Trial.

Spinal cord injury (SCI) attributed to acute intervertebral disc extrusions (IVDEs) is common in dogs and is treated by surgical decompression. Dogs with sensorimotor complete injuries have an incomplete recovery. Pulsed electromagnetic fields (PEMFs) reduce post-operative pain through anti-inflammatory effects and there is growing evidence for neuroprotective effects. This randomized, controlled clinical trial evaluated the effect of PEMF on post-operative pain and neurological recovery in dogs with surgically treated sensorimotor complete SCI attributed to acute IVDE. Sixteen dogs with surgically treated complete thoracolumbar SCI were randomized to receive PEMF (15 min every 2 h for 2 weeks then twice-daily for 4 weeks) or placebo starting immediately after diagnosis. The primary outcome was gait score at 2 weeks. Secondary measures of gait, pain perception, and proprioceptive function were evaluated at 2 and 6 weeks. Plasma glial fibrillary acidic protein (GFAP) concentration was measured as an SCI biomarker. Post-operative pain was quantified by measuring mechanical sensory thresholds (MSTs) at control and surgical sites. There was no significant difference in demographics or GFAP concentration between the two groups at trial entry. There was no difference in primary outcome or in secondary measures of gait, but proprioceptive placing was significantly better at 6 weeks and GFAP concentrations were significantly lower at 2 weeks in the PEMF group. MSTs were significantly higher in the PEMF-treated group. We conclude that PEMF reduced incision-associated pain in dogs post-surgery for IVDE and may reduce extent of SCI and enhance proprioceptive placing. Larger clinical trials are warranted.

Optimal timing and frequency of bone marrow soup therapy for functional restoration of salivary glands injured by single-dose or fractionated irradiation.

Injections of bone marrow (BM) cell extract, known as 'BM soup', were previously reported to mitigate ionizing radiation (IR) injury to salivary glands (SGs). However, the optimal starting time and frequency to maintain BM soup therapeutic efficacy remains unknown. This study tested the optimal starting time and frequency of BM soup injections in mice radiated with either a single dose or a fractionated dose. First, BM soup treatment was started at 1, 3 or 7 weeks post-IR; positive (non-IR) and negative (IR) control mice received injections of saline (vehicle control). Second, BM soup-treated mice received injections at different frequencies (1, 2, 3 and 5 weekly injections). Third, a 'fractionated-dose radiation' model to injure mouse SGs was developed (5 Gy × 5 days) and compared with the single high dose radiation model. All mice (n = 65) were followed for 16 weeks post-IR. The results showed that starting injections of BM soup between 1 and 3 weeks mitigated the effect of IR-induced injury to SGs and improved the restoration of salivary function. Although the therapeutic effect of BM soup lessens after 8 weeks, it can be sustained by increasing the frequency of weekly injections. Moreover, both single-dose and fractionated-dose radiation models are efficient and comparable in inducing SG injury and BM soup treatments are effective in restoring salivary function in both radiation models. In conclusion, starting injections of BM soup within 3 weeks post-radiation, with 5 weekly injections, maintains 90-100% of saliva flow in radiated mice.

The role of low level laser therapy on neuropathic pain relief and interleukin-6 expression following spinal cord injury: An experimental study.

INTRODUCTION: The effect of Low Level Laser Therapy (LLLT) as a non-invasive treatment of spinal cord injury (SCI) is still under investigation. Therefore, the present study aimed to evaluate the effectiveness of LLLT on neuropathic pain and interleukin-6 (IL-6) expression following SCI in male rats. METHODS: 46 adult male rats were divided into 5 groups of control, SCI, treatment with methylprednisolone sodium succinate (MPSS), 1-week LLLT and 2-week LLLT. Animals underwent behavioral evaluations for motor behavior, level of allodynia and hyperalgesia every week. At the end, spinal cord was extracted and IL-6 level was assessed by ELISA method. RESULTS: Treatment with MPSS and 2-week LLLT had led to motor function recovery (df: 24, 145; F=223.5; p <0.001). SCI did not affect mechanical (df: 24, 145; F=0.5; p=0.09), and cold allodynia (df: 24, 145; F=0.3; p=0.17) but significantly increased mechanical (df: 24, 145; F=21.4; p<0.001) and heat hyperalgesia (df: 24, 145; F=16.1; p<0.001). Treatment with MPSS and 1 and 2-weeks LLLT improved mechanical hyperalgesia (p<0.05) and heat hyperalgesia (p<0.01). The increased level of IL-6 following SCI was also compensated by administration of MPSS or LLLT (df: 4, 10; F=8.74; p=0.003). CONCLUSION: Findings show that long periods of LLLT have better effects in improving the complication of SCI. In summation, since LLLT does not cause the side effects of MPSS, long-term use of LLLT may be a proper alternative for MPSS in decreasing post SCI side effects.

Cell extracts from spleen and adipose tissues restore function to irradiation-injured salivary glands.

A cell extract from whole bone marrow (BM), which we named "BM Soup," has the property to restore saliva secretion to irradiation (IR)-injured salivary glands (SGs). However, BM cell harvesting remains an invasive procedure for the donor. The main objective of this study was to test the therapeutic effect of "Cell Soups" obtained from alternate tissues, such as adipose-derived stromal cells (ADSCs) and spleen cells to repair SGs. BM Soup, Spleen Soup, ADSC Soup, or saline (vehicle control) was injected intravenously into mice with IR-injured SGs (13Gy). Results demonstrated that all three cell soups restored 65-70% of saliva secretion, protected acinar cells, blood vessels, and parasympathetic nerves, and increased cell proliferation. Although protein array assays identified more angiogenesis-related growth factors in ADSC Soup, the length of its therapeutic efficiency on saliva flow was less than that of the BM Soup and Spleen Soup. Another objective of this study was to compare "Fresh" versus "Cryopreserved (-80 °C)" BM Soup. It was found that the therapeutic effect of 12-month "Cryopreserved BM Soup" was comparable to that of "Fresh BM Soup" on the functional restoration of IR-injured SGs. In conclusion, both Spleen Soup and ADSC Soup can be used to mitigate IR-damaged SGs.

Restoration of Cognitive Performance in Mice Carrying a Deficient Allele of 8-Oxoguanine DNA Glycosylase by X-ray Irradiation.

Environmental stressors inducing oxidative stress such as ionizing radiation may influence cognitive function and neuronal plasticity. Recent studies have shown that transgenic mice deficient of DNA glycosylases display unexpected cognitive deficiencies related to changes in gene expression in the hippocampus. The main objectives of the present study were to determine learning and memory performance in C57BL/6NTac 8-oxoguanine DNA glycosylase 1 (Ogg1)+/- (heterozygote) and Ogg1+/+ (wild type, WT) mice, to study whether a single acute X-ray challenge (0.5 Gy, dose rate 0.457 Gy/min) influenced the cognitive performance in the Barnes maze, and if such differences were related to changes in gene expression levels in the hippocampus. We found that the Ogg1+/- mice exhibited poorer early-phase learning performance compared to the WT mice. Surprisingly, X-ray exposure of the Ogg1+/- animals improved their early-phase learning performance. No persistent effects on memory in the late-phase (6 weeks after irradiation) were observed. Our results further suggest that expression of 3 (Adrb1, Il1b, Prdx6) out of in total 35 genes investigated in the Ogg1+/- hippocampus is correlated to spatial learning in the Barnes maze.

Spatial memory recovery in Alzheimer's rat model by electromagnetic field exposure.

INTRODUCTION: Although studies have shown a potential association between extremely low frequency electromagnetic fields (ELF-EMFs) exposure and Alzheimer's disease (AD), few studies have been conducted to investigate the effects of weak magnetic fields on brain functions such as cognitive functions in animal models. Therefore, this study aimed to investigate the effect of ELF-EMF exposure (50 Hz, 10 mT) on spatial learning and memory changes in AD rats. METHODS: Amyloid-ß (Aß) 1-42 was injected into lateral ventricle to establish an AD rat model. The rats were divided into six groups: Group I (control); Group II (surgical sham); Group III (AD) Alzheimer's rat model; Group IV (MF) rats exposed to ELF-MF for 14 consecutive days; Group V (Aß injection+M) rats exposed to magnetic field for 14 consecutive days from day 0 to 14 days after the Aß peptide injection; Group VI (AD+M) rats exposed to magnetic field for 14 consecutive days after 2 weeks of Aß peptide injection from 14th to 28th day . Morris water maze investigations were performed. RESULTS: AD rats showed a significant impairment in learning and memory compared to control rats. The results showed that ELF-MF improved the learning and memory impairments in Aß injection+M and AD+M groups. CONCLUSION: Our results showed that application of ELF-MF not only has improving effect on different cognitive disorder signs of AD animals, but also disrupts the processes of AD rat model formation.

Photobiomodulation in Neuroscience: A Summary of Personal Experience.

OBJECTIVE: This review summarizes personal experience with laser photobiomodulation and its potentials for the treatment of peripheral and central nerve system injuries. METHODS AND RESULTS: Laser photobiomodulation was shown to induce nerve cell activation, have a positive effect on metabolism of the nerve cells, and to stimulate nerve sprouting processes. Studies investigating the effects of laser photobiomodulation on injured peripheral nerves in rats reported immediate protective effects which increase the functional activity of the nerve, decrease or prevent scar tissue formation at the injured site, prevent or decrease degeneration in corresponding motor neurons of the spinal cord, and significantly increase axonal growth and myelinization. A direct application of laser on the spinal cord had a positive impact on the corresponding injured peripheral nerve and promoted recovery. A 780-nm laser phototherapy was applied following peripheral nerve reconstruction using a guiding nerve tube. Results showed myelinated axons crossing through the nerve tube and the continuation of axonal sprouting through the tube toward the distal part of the nerve. In a double-blind, placebo-controlled randomized pilot clinical trial in patients with incomplete stable long-term peripheral nerve injury (PNI), 780-nm laser irradiation progressively improved peripheral nerve function and led to substantial functional recovery. Muscle atrophy represents a major challenge in restorative medicine. Laser phototherapy was shown to increase biochemical activity and improve morphological recovery in muscle and, thus, could have a direct therapeutic application, especially during progressive muscle atrophy resulting from PNI. The effectiveness of composite implants of cultured embryonal nerve cells and the role of laser irradiation on regeneration and repair of the completely transected rat spinal cord were examined. Results suggested that laser photobiomodulation treatment accelerates the axonal growth. CONCLUSIONS: The significance of the performed experimental and clinical studies is in the provision of new laser technology in field of cell therapy and its therapeutic value for peripheral nerve and spinal cord injuries. Additional well-designed clinical studies are needed to evaluate the effectiveness and role of laser photobiomodulation treatment in a clinical setting.

Pre-Exercise Infrared Photobiomodulation Therapy (810 nm) in Skeletal Muscle Performance and Postexercise Recovery in Humans: What Is the Optimal Power Output?

BACKGROUND: Photobiomodulation therapy (PBMT) has recently been used to alleviate postexercise muscle fatigue and enhance recovery, demonstrating positive results. A previous study by our research group demonstrated the optimal dose for an infrared wavelength (810 nm), but the outcomes could be optimized further with the determination of the optimal output power. OBJECTIVE: The aim of the present study was to evaluate the effects of PBMT (through low-level laser therapy) on postexercise skeletal muscle recovery and identify the best output power. MATERIALS AND METHODS: A randomized, placebo-controlled double-blind clinical trial was conducted with the participation of 28 high-level soccer players. PBMT was applied before the eccentric contraction protocol with a cluster with five diodes, 810 nm, dose of 10 J, and output power of 100, 200, 400 mW per diode or placebo at six sites of knee extensors. Maximum isometric voluntary contraction (MIVC), delayed onset muscle soreness (DOMS) and biochemical markers related to muscle damage (creatine kinase and lactate dehydrogenase), inflammation (IL-1ß, IL-6, and TNF-α), and oxidative stress (catalase, superoxide dismutase, carbonylated proteins, and thiobarbituric acid) were evaluated before isokinetic exercise, as well as at 1 min and at 1, 24, 48, 72, and 96 h, after the eccentric contraction protocol. RESULTS: PBMT increased MIVC and decreased DOMS and levels of biochemical markers (p < 0.05) with the power output of 100 and 200 mW, with better results for the power output of 100 mW. CONCLUSIONS: PBMT with 100 mW power output per diode (500 mW total) before exercise achieves best outcomes in enhancing muscular performance and postexercise recovery. Another time it has been demonstrated that more power output is not necessarily better.

Low-dose fractionated irradiation promotes axonal regeneration beyond reactive gliosis and facilitates locomotor function recovery after spinal cord injury in beagle dogs.

Injury to the adult central nervous system (CNS) results in the formation of glial scar tissues. Glial scar-induced failure of regenerative axon pathfinding may limit axon regrowth beyond the lesion site and cause incorrect reinnervation and dystrophic appearance of stalled growth after CNS trauma. Glial scars also upregulate chondroitin sulphate proteoglycans (CSPGs) and expression of proinflammatory factor(s) that form a barrier to axonal regeneration. Therefore, interventions for glial scarring are an attractive strategy for augmenting axonal sprouting and regeneration and overcoming the physical and molecular barriers impeding functional repair. The glial reaction occurs shortly after spinal cord injury (SCI) and can persist for days or weeks with upregulation of cell cycle proteins. In this study, we utilised Beagle dogs to establish a preclinical SCI model and examine the efficacy of low-dose fractionated irradiation (LDI) treatment, which was performed once a day for 14 days (2 Gy per dose, 28 Gy in total). Low-dose fractionated irradiation is a stable method for suppressing cell activation and proliferation through interference in the cell cycle. Our results demonstrated that LDI could reduce astrocyte and microglia activation/proliferation and attenuate CSPGs and IL-1ß expression. Low-dose fractionated irradiation also promoted and provided a pathway for long-distance axon regeneration beyond the lesion site, induced reinnervation of axonal targets and restored locomotor function after SCI in Beagle dogs. Taken together, our findings suggest that LDI would be a promising therapeutic strategy for targeting glial scarring, promoting axon regeneration and facilitating reconstruction of functional circuits after SCI.

Effects of Localized X-Ray Irradiation on Peripheral Nerve Regeneration in Transected Sciatic Nerve in Rats.

Low-dose radiation has been used in clinical and experimental models for the prevention of scarring and for fracture healing. There is evidence that low-dose radiation improves the hormesis of various cell types but little is known about its effects on peripheral nerve tissue. In this study, we investigated the beneficial effects of low-dose radiation on the regeneration of transectional peripheral nerve injury in an experimental rat model. Seventy-two male Sprague-Dawley rats received transection injury to the left sciatic nerves, and the nerves were subsequently sutured by epineurium end-to-end anastomosis to restore continuity. Animals were randomly assigned to one of two treatment groups (n = 36/group): 1 Gy X-ray irradiation or control (sham irradiation). Gait analysis, electrophysiological examination and morphological investigations were performed. In addition, Western blot and qRT-PCR were performed to determine the level of vascular endothelial growth factor (VEGF) and growth-associated protein-43 (GAP-43). Content of VEGF and GAP-43 in the regenerated sciatic nerve of the irradiated group was higher than the control group. At 4 to 12 weeks after surgery, the irradiated animals exhibited a significantly improved functional recovery relative to controls. At 12 weeks after surgery, amplitude and conduction velocity of the irradiated group were higher than the control group (P < 0.05). The number of nerve fibers, diameter of axons and morphological structure of the myelin sheath in the irradiated group were superior to those of the control group. These results suggest that low-dose radiation contributed to regeneration and functional recovery after transverse peripheral nerve injury by inducing increased production of VEGF and GAP-43, which promote the axonal regeneration and myelination.

Low-level light emitting diode therapy promotes long-term functional recovery after experimental stroke in mice.

We aimed to investigate the effects of low-level light emitting diode therapy (LED-T) on the long-term functional outcomes after cerebral ischemia, and the optimal timing of LED-T initiation for achieving suitable functional recovery. Focal cerebral ischemia was induced in mice via photothrombosis. These mice were assigned to a sham-operated (control), ischemic (vehicle), or LED-T group [initiation immediately (acute), 4 days (subacute) or 10 days (delayed) after ischemia, followed by once-daily treatment for 7 days]. Behavioral outcomes were assessed 21 and 28 days post-ischemia, and histopathological analysis was performed 28 days post-ischemia. The acute and subacute LED-T groups showed a significant improvement in motor function up to 28 days post-ischemia, although no brain atrophy recovery was noted. We observed proliferating cells (BrdU+ ) in the ischemic brain, and significant increases in BrdU+ /GFAP+ , BrdU+ /DCX+ , BrdU+ /NeuN+ , and CD31+ cells in the subacute LED-T group. However, the BrdU+ /Iba-1+ cell count was reduced in the subacute LED-T group. Furthermore, the brain-derived neurotrophic factor (BDNF) was significantly upregulated in the subacute LED-T group. We concluded that LED-T administered during the subacute stage had a positive impact on the long-term functional outcome, probably via neuron and astrocyte proliferation, blood vessel reconstruction, and increased BDNF expression. Picture: The rotarod test for motor coordination showed that acute and subacute LED-T improves long-term functional recovery after cerebral ischemia.