Blood-brain barrier neurological diseases

Lead, like mercury, causes neurological diseases. The organolead compounds are more toxic than mineral lead salts, since they are non-polar, lipid-soluble, and more readily cross the blood-brain barrier. This disease is related to mental retardation is children, lower performance on I.Q. tests, and hyperactivity. Severe exposure in adults causes irritability, sleeplessness, and irrational behavior. Some have gone as far as to blame anti-social behavior and criminality on sub-clinical Pb poisoning. A correlation between Pb in blood and Pb in air, dust and soils has been observed in many studies. The U.S. Centers for Disease Control has proclaimed a goal of reducing blood lead contents in children below 10 jag/lOOmL. 

High doses can provoke marked adverse effects in patients with neurological disorders, coronary heart disease, or disorders of the pituitary-adrenal axis, especially if the blood-brain barrier has been damaged (for example by a head injury or during intracranial surgery). Nonstandard doses should only be used in experimental work with well-designed safety precautions. 

The authors speculated that the most likely explanation for these observations was linked to the lack of transfer of high-molecular weight soluble receptors and IgG across the blood-brain barrier, implying that control of brain tumor necrosis factor alfa cannot be obtained with monoclonal antibodies. They thought that neurological complications in diseases other than multiple sclerosis might be related to control of tumor necrosis factor alfa in the periphery, resulting in an enhanced contribution of brain-derived tumor necrosis factor alfa or other cytokines, such as interleukin-1. 

DOPA decarboxylase, a pyridoxal phosphate-requiring enzyme, catalyzes the synthesis of dopamine from DOPA. Dopamine is produced in neurons found in certain structures in the brain. It is believed to exert an inhibitory action within the central nervous system. Deficiency in dopamine production has been found to be associated with Parkinson s disease, a serious degenerative neurological disorder (Special Interest Box 14.3). The precursor l-DOPA is used to alleviate the symptoms of Parkinson s disease because dopamine cannot penetrate the blood-brain barrier. (The blood-brain barrier protects the brain from toxic substances. Many polar molecules and ions cannot move from blood capillaries, although most lipid-soluble substances readily pass across. The blood-brain barrier consists of connective tissue and specialized cells called astrocytes that envelop the capillaries.) Once l-DOPA is transported into appropriate nerve cells, it is converted to dopamine. 

Poor access via the blood-brain barrier is the major obstacle that prevents ERT from being applicable to the neuronopathic disorders. The inflammatory cascade that is mediated by CNS storage seen in the gangliosidoses for example, may respond to steroid treatment but unless the neuronal cell lysosomal burden can be reduced, this peripheral and neurological component of the phenotype could dominate the clinical outcome of disease. 

African trypanosomiasis (sleeping sickness) is spread by the tsetse fly and is caused by infection with either Trypanosoma gambiense or T. rbodesiense. Suramin kills the parasites in blood and lymphoid nodes hy an unknown mechanism and Is curative early in the disease. It does not cross the blood—brain barrier and is ineffective when there is neurological involvemenl. 

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