Xingjia Wu

810 nm Wavelength light: An effective therapy for transected or contused rat spinal cord

Light therapy has biomodulatory effects on central and peripheral nervous tissue. Spinal cord injury (SCI) is a severe central nervous system trauma with no effective restorative therapies. The effectiveness of light therapy on SCI caused by different types of trauma was determined.

Single-cell printing to form three-dimensional lines of olfactory ensheathing cells

Biological laser printing (BioLP) is a unique tool capable of printing high resolution two- and three-dimensional patterns of living mammalian cells, with greater than 95% viability. These results have been extended to primary cultured olfactory ensheathing cells (OECs), harvested from adult Sprague-Dawley rats. OECs have been found to provide stimulating environments for neurite outgrowth in spinal cord injury models. BioLP is unique in that small load volumes ( approximately microLs) are required to achieve printing, enabling low numbers of OECs to be harvested, concentrated and printed. BioLP was used to form several 8 mm lines of OECs throughout a multilayer hydrogel scaffold. The line width was as low as 20 microm, with most lines comprising aligned single cells. Fluorescent confocal microscopy was used to determine the functionality of the printed OECs, to monitor interactions between printed OECs, and to determine the extent of cell migration throughout the 3D scaffold. High-resolution printing of low cell count, harvested OECs is an important advancement for in vitro study of cell interactions and functionality. In addition, these cell-printed scaffolds may provide an alternative for spinal cord repair studies, as the single-cell patterns formed here are on relevant size scales for neurite outgrowth.

In vitro and in vivo optimization of infrared laser treatment for injured peripheral nerves.

Repair of peripheral nerve injuries remains a major challenge in restorative medicine. Effective therapies that can be used in conjunction with surgical nerve repair to improve nerve regeneration and functional recovery are being actively investigated. It has been demonstrated by a number of peer reviewed publications that photobiomodulation (PBM) supports nerve regeneration, reinnervation of the denervated muscle, and functional recovery after peripheral nerve injury. However, a key issue in the use of PBM as a treatment for peripheral nerve injury is the lack of parameter optimization for any given wavelength. The objective of this study was to demonstrate that for a selected wavelength effective in vitro dosing parameters could be translated to effective in vivo parameters.

Light Supports Neurite Outgrowth of Human Neural Progenitor Cells In Vitro : The Role of P2Y Receptors

The purpose of this study was to compare the effects of growth factors and 810-nm-wavelength light on the differentiation of normal human neural progenitor cells (NHNPCs) in vitro. Although growth factors are routinely used to study neural stem and progenitor cells in vitro, to date, light has not been used as a replacement for growth factors. This study demonstrates that NHNPCs are not only capable of being sustained by light in the absence of growth factors, but that they are also able to differentiate normally as assessed by neurite formation. The NHNPCs had an up-regulation in the expression of endogenous fibroblast growth factor-2, brain derived neurotrophic factor, and nerve growth factor in response to the light. Suramin, a nonselective P2 receptor antagonist, significantly decreased neurite outgrowth, and P2Y2 and P2Y11 receptors were found to be expressed by the NHNPCs by immunolabeling. Based on these findings, the mechanism by which light supports the NHNPC differentiation is hypothesized to be due to increases in adenosine triphosphate acting via P2Y receptors.

Pulsed Light Irradiation Improves Behavioral Outcome in a Rat Model of Chronic Mild Stress

Transcranial laser therapy (TLT) has been used successfully for the treatment of stroke in animal models and clinical trials. These results support the hypothesis that TLT could be used to treat other central nervous system conditions, such as depression. Current therapy for depression emphasizes pharmaco‐therapeutics. However, these interventions often cause unwanted side effects. Here, TLT as a treatment for depression was studied in a rat model of chronic mild stress (CMS).

Effect of 810 nm light on nerve regeneration after autograft repair of severely injured rat median nerve.

Destruction of large segments of peripheral nerves results in chronic loss of sensation and paralysis. For this type of severe injury, the defect can be bridged by nerve grafts. However, even with state‐of‐the‐art microsurgical techniques, there is minimal recovery of sensation and motor function. Light therapy (LT) has been shown to improve functional outcome after surgical intervention to repair injured nerves using different techniques. Our objective was to investigate the effect of LT on peripheral nerve regeneration and function after severe median nerve injury and microsurgical autologous nerve graft repair using fibrin glue.

Organic light emitting diode improves diabetic cutaneous wound healing in rats

A major complication for diabetic patients is chronic wounds due to impaired wound healing. It is well documented that visible red wavelengths can accelerate wound healing in diabetic animal models and patients. In vitro and in vivo diabetic models were used to investigate the effects of organic light emitting diode (OLED) irradiation on cellular function and cutaneous wound healing. Human dermal fibroblasts were cultured in hyperglycemic medium (glucose concentration 180 mM) and irradiated with an OLED (623 nm wavelength peak, range from 560 to 770 nm, power density 7 or 10 mW/cm2 at 0.2, 1, or 5 J/cm2). The OLED significantly increased total adenosine triphosphate concentration, metabolic activity, and cell proliferation compared with untreated controls in most parameters tested. For the in vivo experiment, OLED and laser (635 ± 5 nm wavelength) treatments (10 mW/cm2, 5 J/cm2 daily for a total of seven consecutive days) for cutaneous wound healing were compared using a genetic, diabetic rat model. Both treatments had significantly higher percentage of wound closure on day 6 postinjury and higher total histological scores on day 13 postinjury compared with control. No statistical difference was found between the two treatments. OLED irradiation significantly increased fibroblast growth factor‐2 expression at 36‐hour postinjury and enhanced macrophage activation during initial stages of wound healing. In conclusion, the OLED and laser had comparative effects on enhancing diabetic wound healing.

Characterization of Macrophage/Microglial Activation and Effect of Photobiomodulation in the Spared Nerve Injury Model of Neuropathic Pain

Objective Neuropathic pain is common and debilitating with limited effective treatments. Macrophage/microglial activation along ascending somatosensory pathways following peripheral nerve injury facilitates neuropathic pain. However, polarization of macrophages/microglia in neuropathic pain is not well understood. Photobiomodulation treatment has been used to decrease neuropathic pain, has anti-inflammatory effects in spinal injury and wound healing models, and modulates microglial polarization in vitro. Our aim was to characterize macrophage/microglia response after peripheral nerve injury and modulate the response with photobiomodulation. Methods Adult male Sprague-Dawley rats were randomly assigned to sham (N = 13), spared nerve injury (N = 13), or injury + photobiomodulation treatment groups (N = 7). Mechanical hypersensitivity was assessed with electronic von Frey. Photobiomodulation (980 nm) was applied to affected hind paw (output power 1 W, 20 s, 41cm above skin, power density 43.25 mW/cm 2 , dose 20 J), dorsal root ganglia (output power 4.5W, 19s, in skin contact, power density 43.25 mW/cm 2 , dose 85.5 J), and spinal cord regions (output power 1.5 W, 19s, in skin contact, power density 43.25 mW/cm 2 , dose 28.5 J) every other day from day 7-30 post-operatively. Immunohistochemistry characterized macrophage/microglial activation. Results Injured groups demonstrated mechanical hypersensitivity 1-30 days post-operatively. Photobiomodulation-treated animals began to recover after two treatments; at day 26, mechanical sensitivity reached baseline. Peripheral nerve injury caused region-specific macrophages/microglia activation along spinothalamic and dorsal-column medial lemniscus pathways. A pro-inflammatory microglial marker was expressed in the spinal cord of injured rats compared to photobiomodulation-treated and sham group. Photobiomodulation-treated dorsal root ganglion macrophages expressed anti-inflammatory markers. Conclusion Photobiomodulation effectively reduced mechanical hypersensitivity, potentially through modulating macrophage/microglial activation to an anti-inflammatory phenotype.

Comparison of the effects of pulsed and continuous wave light on axonal regeneration in a rat model of spinal cord injury.

Light therapy (LT) has been investigated as a viable treatment for injuries and diseases of the central nervous system in both animal models and clinical trials. Based on in vivo studies, LT has beneficial effects on the treatment of spinal cord injury (SCI) [1–3], traumatic brain injury [4], stroke [5–9] and neurodegenerative diseases [10, 11]. Recent clinical trials on stroke have demonstrated that light is safe for the treatment of ischemic stroke in humans [12, 13]. The biomodulatory effects of LT have been investigated to a much greater extent with continuous wave (CW) mode than in pulsed mode. However, there is no clear consensus that one mode is superior to the other. A recent review of the published literature that compared the effects of light in CWor pulsed mode reported that some studies have shown pulsed light to be more effective than CW light, while other studies have shown no effect or a worsening effect with pulsed light compared to no treatment [14]. The studies in which pulsed light was more effective than CW light include LTon wound healing, pain attenuation, bone stimulation and ischemic stroke in animal models and human studies [14]. Lapchak et al. compared CW light with two different frequencies of pulsed light and found that transcranial treatment with both pulsing regimes significantly improved behavioral deficits compared to the CW light [6]. Why pulsed light in some cases improves the outcome of LT is currently unclear, and further investigation is needed. Our previous studies have shown that LT promotes axonal regeneration and functional recovery in both hemisection and contusion models of SCI in rats with CW laser light [2, 3]. The purpose of this study was to compare the effects of CW and pulsed laser light on nerve regeneration in a hemisection model of SCI.

The mechanistic basis for photobiomodulation therapy of neuropathic pain by near infrared laser light

Various irradiances have been reported to be beneficial for the treatment of neuropathic pain with near infrared light. However, the mechanistic basis for the beneficial outcomes may vary based on the level of irradiance or fluence rate used. Using in vivo and in vitro experimental models, this study determined the mechanistic basis of photobiomodulation therapy (PBMT) for the treatment of neuropathic pain using a high irradiance.