White matter damage

Tian, J., Shi, J., Bailey, K., Lendon, C.L., Pickering-Brown, S.M., Mann, D.M.A. (2004) Association between apolipoprotein E E4 allele and arteriosclerosis, cerebral amyloid angiopathy, and cerebral white matter damage in Alzheimer s disease. J. Neurol. Neurosurg. Psychiatry, 75, 696-699. 

Jones DK, Lythgoe D, Horsfield MA, Simmons A, Williams SC, Markus HS (1999) Characterization of white matter damage in ischemic leukoaraiosis with diffusion tensor MRI. Stroke 30 393-397... 

A common feature of brain damage between early gestation and infancy is destruction of this cerebral white matter, the fiber tracts that connect one part of the brain to other parts or to the spinal cord. A common consequence of large-scale white matter damage is a clinical syndrome in which disturbances of motor control are prominent. Cerebral palsy is such a syndrome. 

Rosenberg GA, Sullivan N, Esiri MM. White matter damage is associated with matrix metalloproteinases in vascular dementia. Stroke. 2001 32 1162-1168... 

These are published postmortem examination data on only two cases. Although these are biased towards more severe phenotypes, their importance arises from direct observations of gray and white matter damage, yielding insights into selective neuronal vulnerability in galactosemia. Future posttnortem examination studies... 

In most of these disorders, white matter damage is patchy, and the basal ganglia are not affected. Treatments to protect the brain are few. In some disorders enzyme replacement and substrate reduction are possible, but the efficacy in the brain, an organ protected by the blood-brain barrier, is often poor. 

Diffusion tensor imaging (DTI) and quantitative T-2 MRI were used to characterize ex vivo the white matter damage at 3 and 8 weeks following dorsal column transection (DC Tx) injury at the cervical level C5 of rat spinal cords. " This study demonstrates that quantitative MRI can accurately characterize white matter damage in DC Tx model of injury in rat spinal cord. 

The rate of free fatty acid production in the mammalian brain correlates to the extent of resistance to ischemia. FFA production rate is much lower in the brains of neonatal mammals and poikilothermic animals, organisms that display a greater resistance to cerebral ischemic insults than mature mammals [63]. In addition, within the mammalian brain, FFA release is higher in the gray matter compared with white matter, and there is a greater accumulation of AA in areas of the brain, such as the hippocampus, selectively vulnerable to cerebral ischemic damage. 

White matter hyperintesities in magnetic resonance imaging (MRI) scans reflecting cerebrovascnlar damage and brain hypoperfusion are more severe in ACE-D/D subjects (638). Association of ACE-D/D with vascular dementia has also been reported (615,639), although in some stndies no association of ACE-I/D indel variant with vascnlar dementia was fonnd (640). 

It is more difficult to account for the frequently reported fact that bilateral damage to the white matter immediately inferior to the frontal horns of the lateral ventricles obliterates dreaming (see Solms, 1997 for review). 

The pathological effects seem to involve damage to the gray matter, and possibly the white matter, in the brain. 

The toxic effect is known as histotoxic hypoxia. Cyanide also directly stimulates chemoreceptors, causing hyperpnea. Lack of ATP will affect all cells, but heart muscle and brain are particularly susceptible. Therefore, cardiac arrythmias and other changes often occur, resulting in circulatory failure and delayed tissue ischemic anoxia. Death is usually due to respiratory arrest resulting from damage to the CNS, as the nerve cells of the respiratory control center are particularly sensitive to hypoxia. The susceptibility of the brain to pathological damage may reflect the lower concentration of cytochrome oxidase in white matter. 

One of the intensely debated issues during the past few years was the issue of potential DWI lesion reversibility. Initially, it was believed that DWI abnormalities depict irreversibly damaged tissue in humans, i.e the ischemic core. Only few convincing cases had been reported in the literature with resolution of DWI lesions (mostly small lesions, often located in white matter). There is still no doubt that... 

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