PMID- 20144890
OWN - NLM
STAT- MEDLINE
DCOM- 20100701
LR  - 20211020
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 223
IP  - 2
DP  - 2010 Jun
TI  - Theophylline treatment improves mitochondrial function after upper cervical 
      spinal cord hemisection.
PG  - 523-8
LID - 10.1016/j.expneurol.2010.01.020 [doi]
AB  - The importance of mitochondria in spinal cord injury has mainly been attributed 
      to their participation in apoptosis at the site of injury. But another aspect of 
      mitochondrial function is the generation of more than 90% of cellular energy in 
      the form of ATP, mediated by the oxidative phosphorylation (OxPhos) process. 
      Cytochrome c oxidase (CcO) is a central OxPhos component and changes in its 
      activity reflect changes in energy demand. A recent study suggests that 
      respiratory muscle function in chronic obstructive pulmonary disease (COPD) 
      patients is compromised via alterations in mitochondrial function. In an animal 
      model of cervical spinal cord hemisection (C2HS) respiratory dysfunction, we have 
      shown that theophylline improves respiratory function. In the present study, we 
      tested the hypothesis that theophylline improves respiratory function at the 
      cellular level via improved mitochondrial function in the C2HS model. We 
      demonstrate that CcO activity was significantly (33%) increased in the spinal 
      cord adjacent to the site of injury (C3-C5), and that administration of 
      theophylline (20mg/kg 3x daily orally) after C2HS leads to an even more 
      pronounced increase in CcO activity of 62% compared to sham-operated animals. 
      These results are paralleled by a significant increase in cellular ATP levels 
      (51% in the hemidiaphragm ipsilateral to the hemisection). We conclude that C2HS 
      increases energy demand and activates mitochondrial respiration, and that 
      theophylline treatment improves energy levels through activation of the 
      mitochondrial OxPhos process to provide energy for tissue repair and functional 
      recovery after paralysis in the C2HS model.
CI  - Published by Elsevier Inc.
FAU - Huttemann, Maik
AU  - Huttemann M
AD  - Center for Molecular Medicine and Genetics, Wayne State University School of 
      Medicine, Detroit, MI 48201, USA.
FAU - Nantwi, Kwaku D
AU  - Nantwi KD
FAU - Lee, Icksoo
AU  - Lee I
FAU - Liu, Jenney
AU  - Liu J
FAU - Mohiuddin, Syed
AU  - Mohiuddin S
FAU - Petrov, Theodor
AU  - Petrov T
LA  - eng
GR  - R01 HD035766-09/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100208
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - C137DTR5RG (Theophylline)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Apoptosis/physiology
MH  - Cervical Vertebrae
MH  - Diaphragm/innervation/physiology
MH  - Electromyography
MH  - Electron Transport Complex IV/metabolism
MH  - Energy Metabolism/drug effects
MH  - Female
MH  - Mitochondria/*drug effects/metabolism
MH  - Oxidative Phosphorylation/drug effects
MH  - Phosphodiesterase Inhibitors/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recovery of Function/drug effects
MH  - Respiratory Mechanics/physiology
MH  - Spinal Cord Injuries/*drug therapy/*metabolism/physiopathology
MH  - Theophylline/*pharmacology
PMC - PMC2864313
MID - NIHMS177874
EDAT- 2010/02/11 06:00
MHDA- 2010/07/02 06:00
PMCR- 2011/06/01
CRDT- 2010/02/11 06:00
PHST- 2009/08/10 00:00 [received]
PHST- 2010/01/28 00:00 [revised]
PHST- 2010/01/31 00:00 [accepted]
PHST- 2010/02/11 06:00 [entrez]
PHST- 2010/02/11 06:00 [pubmed]
PHST- 2010/07/02 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - S0014-4886(10)00040-3 [pii]
AID - 10.1016/j.expneurol.2010.01.020 [doi]
PST - ppublish
SO  - Exp Neurol. 2010 Jun;223(2):523-8. doi: 10.1016/j.expneurol.2010.01.020. Epub 
      2010 Feb 8.