Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...
Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...
Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...
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AIMS OF THE PRESENT THESIS<br />
The ma<strong>in</strong> objectives <strong>of</strong> this thesis were distributed <strong>in</strong> three chapters as follows:<br />
Chapter 1<br />
AIMS<br />
The first pr<strong>in</strong>cipal aim is to determ<strong>in</strong>e the k<strong>in</strong>etics <strong>of</strong> the <strong>oxidative</strong> damage <strong>in</strong>duced <strong>in</strong> a<br />
6-OHDA model <strong>of</strong> PD and quantify the result<strong>in</strong>g <strong>oxidative</strong> effects <strong>in</strong> order to set up the<br />
accurate post-<strong>in</strong>jection time when study<strong>in</strong>g the <strong>oxidative</strong> effects <strong>of</strong> <strong>alum<strong>in</strong>ium</strong>. To<br />
achieve this aim we have stablished the follow<strong>in</strong>g specific objectives:<br />
1) To analyse the time-course <strong>of</strong> the <strong>oxidative</strong> damage caused by unilateral and<br />
<strong>in</strong>trastriatal adm<strong>in</strong>istration <strong>of</strong> 6-OHDA (6 μg <strong>in</strong> 5 μl <strong>of</strong> sterile sal<strong>in</strong>e conta<strong>in</strong><strong>in</strong>g<br />
0.2% ascorbic acid) <strong>in</strong> both the ipsilateral and contralateral sides <strong>of</strong> both striatum<br />
and ventral midbra<strong>in</strong> <strong>of</strong> the rat.<br />
2) To quantify the changes observed <strong>in</strong> the <strong>in</strong>dices <strong>of</strong> lipid peroxidation (TBARS) and<br />
<strong>oxidative</strong> status <strong>of</strong> prote<strong>in</strong>s (PCC and PTC) <strong>in</strong> the time-course <strong>of</strong> bra<strong>in</strong> <strong>oxidative</strong><br />
damage <strong>in</strong>duced by 6-OHDA <strong>in</strong>jection <strong>in</strong> the experimental model <strong>of</strong> PD mentioned<br />
above.<br />
Chapter 2<br />
The second ma<strong>in</strong> objective is to elaborate a dosage procedure that ensures a significant<br />
accumulation <strong>of</strong> <strong>alum<strong>in</strong>ium</strong> <strong>in</strong>to the bra<strong>in</strong> and to establish its exact distribution <strong>in</strong><br />
different areas <strong>of</strong> the rat bra<strong>in</strong>. In this case, the specific objective is:<br />
3) To evaluate the precise regional accumulation <strong>of</strong> the absorbed <strong>alum<strong>in</strong>ium</strong> <strong>in</strong><br />
cerebellum, ventral midbra<strong>in</strong>, cortex, hippocampus and striatum <strong>of</strong> rats follow<strong>in</strong>g<br />
the use <strong>of</strong> two different adm<strong>in</strong>istration routes, oral and <strong>in</strong>traperitoneal.<br />
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