The potential of light therapy for central nervous system injury and disease.

Light as a neuro-restorative and=or neuro-protective therapy for the treatment of injury and diseases of the central nervous system (CNS) is a novel concept that is rapidly gaining attention. The earliest reports on the use of light for the treatment of CNS injury were the pioneering experiments of Shimon Rochkind. Rochkind and colleagues used 780-nm wavelength laser irradiation in a number of models of spinal cord injury (SCI) and reported enhanced axonal sprouting and spinal cord repair. What was amazing about this research and hard for many people to accept was the claim that light applied transcutaneously could penetrate to the level of the spinal cord and alter the response of the spinal cord to injury. My laboratory, in conjunction with Drs. Waynant and Ilev of the U.S. Food and Drug Administration, was the first to definitively show that light applied transcutaneously penetrates to the level of the spinal cord. In a series of experiments on anesthetized Sprague Dawley rats, a broadband light source was directed at the surface of the skin in the region of the low thoracic vertebral level. A smart, tissue-activated optical fiber probe attached to a spectrophotometer was inserted sequentially into tissue layers from the skin to the spinal cord and a transmission spectrum in the range of 500–1200 nm was collected at each layer. Analysis of the transmission spectra revealed that the penetration was highest through all tissue layers overlying the spinal cord and through blood between the 770and 820-nm wavelengths. The peak transmission was at 810 nm. Further analysis showed 98% of 810-nm light was transmitted through water. For SCI my laboratory has shown that 810-nm light is an effective therapy in both dorsal hemisection and contusion rodent models. The noninvasive transcutaneous application of 810-nm light at the injury site caused a significant increase in the number of regenerating corticospinal tract axons and the length of axonal regrowth. Functional recovery was achieved with ladder crossing time and angle of hind paw rotation returning to baseline levels 9 wk post-injury. Light therapy (LT) significantly decreased the invasion of cells involved in secondary damage to the spinal cord, including macrophages=activated microglia and T lymphocytes from 48 h to 5 wk post-injury, and astrogliosis was reduced at early time points.7 LT acutely applied after SCI also resulted in a statistically significant suppression of proinflammatory cytokine and chemokine expression and in a significant alteration in a subset of genes involved in the immune response, cellular proliferation, and growth factor receptors.9,10 These data provide evidence that light exerts specific ameliorative molecular effects on the response of cells in the CNS to traumatic injury leading to immunosuppression and alteration of the secondary injury response and progression of the injury process. Additionally, optical measurements in human cadavers revealed that 810-nm light penetrates to the level of the spinal cord (J.J. Anders; USUHS, unpublished results). Based on these data, 810-nm light is an effective wavelength for treatment of the CNS. Recent studies in our laboratory and others have documented that 810-nm and similar (808-nm) wavelength light applied to the scalp readily passes through the skull and into the brain and is effective in treating injury to the brain. Transcranial laser therapy (TLT) applied either 4–6 h or 24 h after ischemic stroke in rats and rabbits caused a significant improvement in neurological score compared to control animals. Oron et al. demonstrated that noninvasive transcranial application of light irradiation improves shortand long-term behavioral function and reduces brain tissue loss after traumatic brain injury. In fact, LT was recently shown to be safe and effective for treatment of humans within 24 h of stroke onset and a 660 patient NEST-2 study showed similar safety outcomes and a trend toward efficacy. TLT holds promise for becoming the new gold standard therapy for acute, mild stroke. Currently there is great interest in using TLT for neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). These disorders are particularly attractive as candidates for TLT based on current evidence indicating the role of mitochondrial dysfunction and ATP depletion, oxidative stress, proinflammatory factors, and apoptosis among the cascade of events leading to neuronal death. Since light can alter mitochondrial function, oxidative stress, pro-inflammatory factors, and rescue injured and=or dying neurons, TLT is a potential therapy for neurodegenerative disorders. Using an in vitro model of PD, light was reported to significantly increase cellular ATP, decrease the number of neurons undergoing cell death, and significantly reduce the expression of reactive oxygen and reactive nitrogen species in rotenoneand