Low-level light therapy aids traumatic brain injury [Attachment]

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MicrosoftInternetExplorer4 Low-level lighttherapy aids traumatic brain

injury

http://spie.org/x47857.xml

Hamblin, Ying-Ying Huang, Quihe Wu, Weijun Xuan,Takahiro Ando, Tao Xu,

Sulbha Sharma and Gitika Kharkwal

 

One exposure toa near-IR laser four hours after a head trauma significantly

improvesneurological performance and reduces lesion size.

 

5 May 2011, SPIE Newsroom.

Traumaticbrain injury (TBI) caused by falls, motor vehicle accidents, and

violence leadsto skull fractures, intracranial hemorrhages, elevated

intracranial pressure,and cerebral contusion. Severe and moderate TBI,

accidental or inflicted, is amajor health and socio-economic problem throughout

the world, especially inchildren and young adults.

Despite promisingpreclinical data, most therapeutic trials for TBI performed in

recent yearshave not demonstrated any significant improvement in outcomes.1

Because of thisdisappointing state of affairs, a plethora of experimental

therapies that arenot based on standard pharmaceutical agents have been

investigated,2 including severalphysical treatments.3

Low-level lasertherapy (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. Itsexperimental applications have broadenedto include serious

diseases such as heartattack,4stroke,5 and spinal cord injury.6 LLLT may

havebeneficial effects in the acute treatmentof TBI by increasing mitochondrial

respiration, activating transcriptionfactors, reducing key inflammatory

mediators, inhibiting apoptosis (programmedcell death), stimulating

angiogenesis, and increasing neurogenesis7 (see Figure 1).

Figure 1. Possible mechanisms of transcraniallow-level laser therapy (LLLT) for

traumatic brain injury (TBI). Mitochondrialsignaling causes increased neuronal

survival; lowered edema, inflammation andexcitotoxicity; and increased

angiogenesis, neurotrophins, and neuralprogenitor cells. ROS: Reactive oxygen

species. NO: Nitric oxide. NGF: Nervegrowth factor. BDNF: Brain-derived

neurotrophic factor. NT-3: Neurotrophin-3.

 

We studied the effect of an 810nm laser on several cellular processes in primary

corticalneurons cultured from mouse embryonic brains. We found that at low

fluences(0.3–3Jcm2) mitochondrial respiration was stimulated, as shown bythe

increase in adenosine triphosphate (ATP), Ca2+, andmitochondrial membrane

potential. This, in turn, generated low amounts ofreactive oxygen species (ROS)

and nitric oxide (NO) that activated signalingpathways and gene transcription

without causing cytotoxicity (see Figure 2). At 10J/cm2, thestimulation of these

parameters was reduced because instead of activatingmitochondrial respiration,

they damaged enzymes. At 30J/cm2, severemitochondrial damage occurred, leading

to a second large release of ROS and NOand presumably apoptosis and cytotoxicity

(although this study did not makethose measurements).8

 

 

Figure 2. Effectof 810nm laser on levels of reactive oxygen species (A-C),

nitric oxiderelease (D-F), intracellular calcium (G-I), mitochondrial membrane

potential(J-L), and adenosine triphosphate (M) in primary cultured mouse

corticalneurons.

 

 

We also tested LLLT in two mouse models of TBI. In a closedhead-impact model,

the scalp is opened surgically and a weight dropped onto theexposed skull

followed by scalp closure. We tested four different laserwavelengths using

exactly the same laser parameters in each case (spot-size,fluence, and

irradiance). The data in Figure 3 show that beginning on day 5 forthe 810nm

laser and day 9 for 665nm one, there was a significantdifference in the

neurological severity score (NSS) of the LLLT group comparedto the control. The

improvement became relatively larger and more significantas time progressed.

Although there was a trend towards improvement at middletime points, with the

980nm laser itnever became significant and in the case of the 730nm laser there

was no improvement at all.9 The controlled corticalimpact model involves opening

the scalp and using a trephine to create acraniotomy and expose the dura. A

hydraulic piston was then used to form acontrolled lesion in the cortex. Figure

4 shows LLLT may reduce the braindamage area (stained withtriphenyltetrazolium

chloride) at three days.

 

Figure 3. Neurological severity scores (NSS) over four weeks of mousegroups with

closed head TBI treated with a single exposure to lasers ofdifferent wavelengths

(36J/cm2at 150mW/cm2) four hoursafter TBI.

 

 

 

Figure 4. Triphenyltetrazolium chloride (viabilitystaining) of controlled

cortical impact TBI model treated with LLLT.

 

 

The remarkable effects of LLLT in remedying central nervous system (CNS) damage

in a non-invasive mannerwith little evidence of any adverse side effects suggest

that its applicationwill only increase. Advances in understanding the molecular

and cellular basisfor red and near-IR light on cellsand tissues will only serve

to increase the acceptance of LLLT by the medicalprofession at large. If LLLT

can make even a small contribution to mitigatingthe loss of life, suffering,

disability, and financial burden caused by CNSdisorders, the research efforts

will be worthwhile.

 

 

Hamblin, Ying-Ying Huang, QuiheWu, Weijun Xuan, Takahiro Ando, Tao

Xu, SulbhaSharma, Gitika Kharkwal

Massachusetts General Hospital(MGH)

Boston, MA

Hamblin is a principal investigator at the WellmanCenter for

Photomedicine at MGH and anassociate professor of dermatology at Harvard Medical

School. His researchprogram in photodynamic therapy and low-level laser therapy

is supported by theNational Institutes of Health, Congressionally Directed

Medical ResearchPrograms, and Center for Integration of Medicine and Innovative

Technology. Hehas published more than 125 peer-reviewed articles.

 

References:

 

1. R. K. Narayan, Clinical trials in head injury, JNeurotrauma 19, no. 5, pp.

503-557, 2002.

 

2. J. S. Jennings, A. M. Gerber, M. L. Vallano,Pharmacological strategies for

neuroprotection in traumatic brain injury, MiniRev. Med. Chem. 8, no. 7, pp.

689-701, 2008.

 

3. K. R. Diller, L. Zhu, Hypothermia therapy for braininjury, Annu. Rev. Biomed.

Eng. 11, pp. 135-62, 2009.

 

4. U. Oron, Low-energy laser irradiation reduces formation ofscar tissue after

myocardial infarction in rats and dogs, Circulation103, no. 2, pp. 296-301,

2001.

 

5. Y. Lampl, Laser treatment for stroke, Expert Rev.Neurother. 7, no. 8, pp.

961-5, 2007.

 

6. X. Wu, 810nm Wavelength light: an effective therapy fortransected or contused

rat spinal cord, Lasers Surg. Med. 41, no. 1, pp.36-41, 2009.

 

7. J. T. Hashmi, Role of Low-Level Laser Therapy inNeurorehabilitation, Phys.

Med. & Rehab. 2, pp. S292-S305, 2010.

 

8. G. B. Kharkwal, Effects of 810nm laser on mouse primarycortical neurons,

Proc. SPIE 7887, pp. 788707, 2011. doi:10.1117/12.876664

 

9. Q. Wu, Low level laser therapy for traumatic brain injury,Proc. SPIE 7552,

pp. 755206-1, 2010. doi:10.1117/2.1200906.1669