Low-level light therapy aids traumatic brain injury

Abstract

Traumatic brain injury (TBI) caused by falls, motor vehicle accidents, and violence leads to skull fractures, intracranial hemorrhages, elevated intracranial pressure, and cerebral contusion. Severe and moderate TBI, accidental or inflicted, is a major health and socio-economic problem throughout theworld, especially in children and young adults. Despite promising preclinical data, most therapeutic trials for TBI performed in recent years have not demonstrated any significant improvement in outcomes.1 Because of this disappointing state of affairs, a plethora of experimental therapies that are not based on standard pharmaceutical agents have been investigated,2 including several physical treatments.3 Low-level laser therapy (LLLT), also known as photobiomodulation, is an emerging therapeutic approach in which cells or tissues are exposed to low-levels of red and near-IR light. Its experimental applications have broadened to include serious diseases such as heart attack,4 stroke,5 and spinal cord injury.6 LLLT may have beneficial effects in the acute treatment of TBI by increasing mitochondrial respiration, activating transcription factors, reducing key inflammatory mediators, inhibiting apoptosis (programmed cell death), stimulating angiogenesis, and increasing neurogenesis7 (see Figure 1). We studied the effect of an 810nm laser on several cellular processes in primary cortical neurons cultured from mouse embryonic brains. We found that at low fluences (0.3–3Jcm2/ mitochondrial respiration was stimulated, as shown by the increase in adenosine triphosphate (ATP), Ca2C; and mitochondrial membrane potential. This, in turn, generated low amounts of reactive oxygen species (ROS) and nitric oxide (NO) that activated signaling pathways and gene transcription without causing cytotoxicity (see Figure 2). At 10J/cm2; the stimulation of these parameters was reduced because instead of activating mitochondrial respiration, they damaged Figure 1. Possible mechanisms of transcranial low-level laser therapy (LLLT) for traumatic brain injury (TBI). Mitochondrial signaling causes increased neuronal survival; lowered edema, inflammation and excitotoxicity; and increased angiogenesis, neurotrophins, and neural progenitor cells. ROS: Reactive oxygen species. NO: Nitric oxide. NGF: Nerve growth factor. BDNF: Brain-derived neurotrophic factor. NT-3: Neurotrophin-3.