Neurologic repair

Chopp, M., Chan, P. H., Hsu, C. Y., Cheung, M. E. and Jacobs, T. P. DNA damage and repair in central nervous system injury National Institute of Neurological Disorders and Stroke Workshop Summary. Stroke 27 363-369,1996. 

Reader in Molecular Neurology, Department of Clinical Neurosciences and Centre for Brain Repair University of Cambridge Robinson Way Cambridge CB2 2PY United Kingdom... 

In a NIOSH Health Hazard Evaluation of refrigeration workers exposed far below the threshold limit values (TLVs) for chloropentafluoroethane and chlorodifluoromethane, 27 workers were medically evaluated. Seventy-one percent complained of dizziness and lightheadedness compared with twenty-one percent of controls. Palpitations were reported in 36% of exposed and none of the non-exposed workers. No clinical neurological or electroneurophysiological abnormalities were detected in eight of the refrigeration repair workers followed for 3 years during continuous employment. ... 

Ataxia telangiectasia is an autosomal recessive disease characterized by neurologic, endocrine, and hepatic abnormalities, as well as a predisposition to malignancy (119). The defect has been traced to a gene on chromosome 11, the ATM gene that codes for a phosphatidylinositol 3-kinase-like protein which is related to the catalytic subunit of DNA-dependent protein kinase. This protein has a role in signal transduction, DNA repair, and control of the cell cycle (120). Affected patients have a defect in cell-mediated immunity. A decrease in semm IgA is seen in a majority of affected patients. IgG2 or total IgG and IgE levels may be decreased, with an increase in IgM. Patients are susceptible to chronic respiratory... 

Important for growth and repair of neurons. Its disturbed metabolism is associated with neurological disorders such as Alzheimer s disease and Bipolar Disorder... 

When Pol II transcription halts at the site of a DNA lesion, TFIIH can interact with the lesion and recruit the entire nucleotide-excision repair complex. Genetic loss of certain TFIIH subunits can produce human diseases. Some examples are xeroderma pigmentosum (see Box 25-1) and Cockayne s syndrome, which is characterized by arrested growth, photosensitivity, and neurological disorders. ... 

Kim SU. Human neural stem cells genetically modified for brain repair in neurological disorders. Neuropathology. 2004 24 159-171. 

Petito CK, Feldmann E, Pulsinelli WA, Plum F (1987) Delayed hippocampal damage in humans following cardiorespiratory arrest. Neurology 37 1281-1286 Pevny L, Rao MS (2003) The stem-cell menagerie. Trends Neurosci 26 351-359 Picard-Riera N, Nait-Oumesmar B, Baron-Van Evercooren A (2004) Endogenous adult neural stem cells limits and potential to repair the injured central nervous system. J Neurosci Res 76 223-231... 

The neuroprotective properties of mild hypothermia have been demonstrated in numerous experimental animal models. Research in this area has been conducted for many years, yet the mechanisms of cerebral protection by mild hypothermia remain unclear and continue to be the subject of intense investigation. The neuroprotective effects of mild hypothermia have been attributed to alterations in metabolic rate (24), neurotransmitter release (25-27), activity of protein kinases (28), resynthesis of cellular repair proteins (29), cerebral blood flow (30), preservation of the blood-brain barrier (BBB) (31), attenuation of inflammatory processes (32,33), and decreases in free radical production (34). Although these may all be components of a complex cascade leading to neurologic injury, it has become increasingly clear that the primary mechanism of action of hypothermia may be different at various temperatures as well as under different ischemic and traumatic conditions. 

B. C. White, L. I. Grossman, and G. S. Krause, Brain Injury by Global Ischemia and Reperfusion A Theoretical Perspective on Membrane Damage and Repair, Neurology 43 (1993) 1656-1665. 

Rotterdam (79)studies, provide contradictory results. The presence of ApoE e4 allele(s) is associated with worse neurological impairment in head injury or stroke patients, suggesting that ApoE4 might actually impair neural tissue repair (80). 

White, B. C., Grossman, L. I., and Krause, G. C., Brain injury by global ischemia and reperfusion a theoretical perspective on membrane damage and repair, Neurology, 43, 1656, 1993. 

Three examples demonstrate the importance of E3 proteins to nor-mal cell tunction. Proteins that are not broken down owing to a de-fective E3 may accumulate to create a disease of protein aggregation such as juvenile and early-onset Parkinson disease. A defect in another member of the E3 family causes Angelman syndrome, a severe neurological disorder diaracterized by mental retardation, absence of speech, uncoordinated movement, and hyperactivity. Conversely, uncontrolled protein turnover can create dangerous pathological conditions. For example, human papilloma virus (HPV) encodes a protein that activates a specific E3 enzyme. The enzyme ubiquitinates the tumor suppressor p53 and other proteins that control DNA repair, which are then destroyed. The activation of this E3 enzvme is observed in more than 90 /u of cervical carcinomas. Thus, the... 

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