Influence of lead on blood brain

barrierEcological Physiology

Name:Pavan Barot :Megha Patel Group 218

CFU

• Lead has been recognized as a poison for millennia and has been the focus of public health regulation in much of the developed world for the better part of the past century. The nature of regulation has evolved in response to increasing information provided by vigorous scientific investigation of lead’s effects. In recognition of the particular sensitivity of the developing brain to lead’s pernicious effects, much of this legislation has been addressed to the prevention of childhood lead poisoning.

• The present review discusses the current state of knowledge concerning the effects of lead on the cognitive development of children. Addressed are the reasons for the child’s exquisite sensitivity, the behavioural effects of lead, how these effects are best measured, and the long‐term outlook for the poisoned child. Of particular importance are the accumulating data suggesting that there are toxicological effects with behavioural concomitants at exceedingly low levels of exposure. 

•  In addition, there is also evidence that certain genetic and environmental factors can increase the detrimental effects of lead on neural development, thereby rendering certain children more vulnerable to lead neurotoxicity. The public health implications of these findings are discussed.

Blood-brain barrier (BBB) function was assessed in 19-21-day-old rats exposed to low level lead from birth. Newborn rats received lead via milk from lactating dams given drinking water containing 0.1% lead acetate [Pb(Ac)2]. The treatment regime produced lead levels in the neonates within the range 20-80 micrograms dl-1 blood, without affecting growth. Cerebrovascular permeability (PS-product) to the diffusion-limited solute mannitol was unchanged in six regions of the cerebral hemisphere, the cerebellum and the brainstem, suggesting that barrier integrity was not affected by the low dose lead treatment. Regional cerebrovascular permeability to nutrient tracers representing seven BBB transport classes was not impaired by lead treatment. However, the PS estimates for the amino acids lysine and histidine and for thiamine were greater than control in some regions of the cerebral hemisphere. These alterations in nutrient supply to the brain may reflect altered substrate utilization associated with repair processes or delayed maturation of the CNS.

Altitude In the nervous system, lead blocks the receptor

know as N-methyl-D-aspartate, an effective receptor involved in the maturation of brain plasticity, which are changes that occur in brain organization. The blockage of this receptor in the brain leads to the interruption of long-term potentiation, which, in turn, limits the permanent intake and storage of newly learned knowledge. Also, elevated blood lead levels (BLLs) impair the blood-brain barrier function (1).

• The blood-brain barrier is made up of many endothelial cells connected by tight junctions. These endothelial cells become surrounded by astrocytes, which actually outnumber neurons in brain; in the process, the astrocytes weave their way in between the axons and dendrites. Studies have shown that the toxicity of lead plays a major role in the communication between the astrocytes and the endothelial cells (1)

Conclusion

• The blood-brain barrier has a very important function in maintaining the fluid environment of the nervous system. While other organs in the body transport molecules by the simple method of diffusion, the blood-brain barrier is very persnickety in that it selects only certain and essential water-soluble molecules (essential amino acids, glucose, calcium, sodium, and potassium) to be transported by carriers in the plasma membrane. This intricacy in the transportation of molecules through the blood-brain barrier explains the barrier’s susceptibility to trauma due to dangerous toxicants (see Figure 1) (2).

• When the blood-brain barrier is exposed to high levels of lead concentration, plasma moves into the interstitial spaces of the brain, resulting in edema. High blood lead toxicity of the CNS results in encephalopathy and edema that mainly affects the cerebellum of the brain (3). Edema causes extreme pressure increases in the brain, which can lead to irreversible brain damage (4). This type of brain damage includes decreased attention, affects visual-motor reasoning skills and social behavior and can damage mathematic skills and reading abilities (5). Studies have also shown that lead intoxication drastically decreases cognitive ability, resulting in a loss of IQ points anywhere from 0 to 5 per increase of 10 μg/dl in BLLs 

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