The Future of Combinational Therapy in the Treatment of Traumatic Brain Injury

Rehabilitation for Traumatic Brain Injury. Walter M. High, Jr., Angelle M. Sander, Margaret A. Struchen, and Karen A. Hart (Eds.). 2005. New York: Oxford University Press. 368 pp., $69.50 (HB).Rehabilitation for Traumatic Brain Injury, the final product of a 2003 conference that assembled national experts on traumatic brain injury (TBI) rehabilitation, was written to “bring into one volume a concise and authoritative account of what is currently known in the field of TBI rehabilitation.” It is intended for TBI clinicians and researchers including neuropsychologists, physiatrists, neurologists, neurosurgeons, psychiatrists, and rehabilitation therapists. The volume is impressive for the number of chapter authors who are nationally recognized experts on various aspects of TBI rehabilitation (e.g., Drs. Prigatano, Malec, Corrigan, Levin, Boake, Diller, Sohlberg, and Cicerone), as well as the broad and inclusive range of topics covered.

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Progress in Clinical Neurosciences: Therapeutic Hypothermia in Severe Traumatic Brain Injury

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100003000 ◽

2003 ◽

Vol 30 (4) ◽

pp. 307-313 ◽

Cited By ~ 4

Author(s):

David A. Zygun ◽

Christopher J. Doig ◽

Roland N. Auer ◽

Kevin B. Laupland ◽

Garnette R. Sutherland

Keyword(s):

Traumatic Brain Injury ◽

Clinical Trials ◽

Brain Injury ◽

Therapeutic Hypothermia ◽

Severe Traumatic Brain Injury ◽

Clinical Studies ◽

Current Evidence ◽

Optimal Temperature ◽

Widespread Acceptance ◽

The Future

Severe traumatic brain injury (sTBI) is a relatively common problem with few therapies proven effective. Despite its use for over 50 years, therapeutic hypothermia has not gained widespread acceptance in the treatment of sTBI due to conflicting results from clinical trials. This review will summarize the current evidence from animal, mechanistic and clinical studies supporting the use of therapeutic hypothermia. In addition, issues of rewarming and optimal temperature will be discussed. Finally, the future of hypothermia in sTBI will be addressed.

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Combinational Therapy Using Hypothermia and the Immunophilin Ligand FK506 to Target Altered Pial Arteriolar Reactivity, Axonal Damage, and Blood–Brain Barrier Dysfunction after Traumatic Brain Injury in Rat

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2010.208 ◽

2010 ◽

Vol 31 (4) ◽

pp. 1143-1154 ◽

Cited By ~ 27

Author(s):

Yasutaka Oda ◽

Guoyi Gao ◽

Enoch P Wei ◽

John T Povlishock

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Blood Brain Barrier ◽

Vascular Reactivity ◽

Axonal Injury ◽

Brain Barrier ◽

Therapeutic Window ◽

Barrier Dysfunction ◽

Combinational Therapy ◽

Blood Brain

This study evaluated the utility of combinational therapy, coupling delayed posttraumatic hypothermia with delayed FK506 administration, on altered cerebral vascular reactivity, axonal injury, and blood–brain barrier (BBB) disruption seen following traumatic brain injury (TBI). Animals were injured, subjected to various combinations of hypothermic/FK506 intervention, and equipped with cranial windows to assess pial vascular reactivity to acetylcholine. Animals were then processed with antibodies to the amyloid precursor protein and immunoglobulin G to assess axonal injury and BBB disruption, respectively. Animals were assigned to five groups: (1) sham injury plus delayed FK506, (2) TBI, (3) TBI plus delayed hypothermia, (4) TBI plus delayed FK506, and (5) TBI plus delayed hypothermia with FK506. Sham injury plus FK506 had no impact on vascular reactivity, axonal injury, or BBB disruption. Traumatic brain injury induced dramatic axonal injury and altered pial vascular reactivity, while triggering local BBB disruption. Delayed hypothermia or FK506 after TBI provided limited protection. However, TBI with combinational therapy achieved significantly enhanced vascular and axonal protection, with no BBB protection. This study shows the benefits of combinational therapy, using posttraumatic hypothermia with FK506 to attenuate important features of TBI. This suggests that hypothermia not only protects but also extends the therapeutic window for improved FK506 efficacy.

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