الفهرس 
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Abstract
In this work, the protective effect of aldose reductase inhibitors on diabetic CNS complications under normal and ischemic conditions was studied.
To establish this we used two experimental models; diabetes induced by streptozotocin injection and rats were given two months to develop CNS complications then treated with aldose reductase inhibitors (20mg /kg) either ferulic acid or trans cinnamaldehyde oil for another two months and then half of the rats were subjected to MCAO.
In another model; rats were given trans cinnamaldehyde oil (TCA) for ten days and then subjected to MCAO.
The structural alterations of the CNS system associated with diabetes under normal and ischemic conditions were assessed by observing the alteration of behavior in y- maze and elevated plus maze and also vascular alteration evidenced by systolic and diastolic blood pressure. Blood glucose, body weight and serum level of advanced glycation end products (AGEs) were also determined and mortality rate was recorded after ischemia induction.
In order to elucidate the possible mechanisms that explain our results, sensiomotor deficit was assessed , infarct volume , brain edema and evans blue extravasation, serum level of advanced glycation end products (AGEs) andmolandialdehyde level and expression of iNOS and TNF-α were also measured and IL-1β was determined by ELISA techniques.
The main findings can be summarized as follows:
Part 1:
• Diabetes induction was associated with a decrease in body weight and elevation in blood glucose, systolic blood pressure, diastolic blood pressure, serum advancdglycation end products and transfer latency in elevated plus maze and a decrease in y-maze score and higher mortality following stroke induction.
• Treatment with ferulic acid (20 mg/kg) significantly reduced the elevation in diastolic blood pressure, AGEs and transfer latency in elevated plus maze, increased y-maze score. And lead to lower mortality following stroke induction.
• Treatment with trans cinnamaldehyde (20mg/kg) significantly reduced AGEs, transfer latency in elevated plus maze, increased y-maze score. And lower mortality following stroke induction.
• Treatment with gliclazide (10 mg/kg )significantly reduced the elevation in systolic and diastolic blood pressure, AGEs ,transfer latency in elevated plus maze, increased y-maze score. And lead to lower mortality following stroke induction.
Part 2:
• Ischemia lead to significant elevation in neurological deficit , infarct volume, brain edema, evans blue extravasation, AGEs , molandialdehyde serum level and level of iNOS, TNF-α.
• Treatment with trans cinnamaldehyde oil lead to significant decrease in neurological deficit , infarct volume, brain edema, evans blue extravasation, AGEs , molandialdehyde serum level and level of iNOS, TNF-α and IL-1β.
• Treatment with cerebrolysin lead to significant decrease in, infarct volume, evans blue absorbance, AGEs, molandialdehyde serum level and level of iNOS, TNF-α and IL-1β.
from the previous findings it may be concluded that:
Part 1
• Ferulic acid alleviated the hypertensive effects of diabetes via antiglycation, antioxidant, anti-inflammatory properites. Ferulic acid offsets dementia and cognitive decline associated with diabetes through neuroprotection against oxidative stress and improved mortality percentage after ischemia induction.
• Cinnamaldehyde also ameliorated cognitive decline associated with diabetes via its antioxidant and anti-inflammatory actions and improved mortality percentage after ischemia induction.
Part 2
• Trans cinnamaldehyde oil lead to improvement in neurological deficit and infarct volume this may be due to improvement of oxidative stress and decrease iNOS and pro-inflammatory cytokines ( il-1β and tnf-α).
• Cinnamaldehyde through its antioxidant effects ameliorates oxidative stress and lipid peroxidation which lead to cell death associated with ischemia and decreases AGEs elevated in ischemia conditions by free radical scavenger and antioxidant properites .
• Also cinnamaldehyde can suppress expression of iNOS and pro inflammatory mediators iL-1β and TNF-α. This occurs due to anti-inflammatory actions of cinnamaldehyde.
• Also cinnamaldehyde improved BBB disruption via IL-1β inhibition. This improvement in BBB permability lead to improvement in brain edema.
Recommediation
• Delay should be avoided in the treatment of diabetes as it can stimulate vascular and CNS complications.
• The study suggests aldose reductase inhibitors as a novel therapeutic target for protection against CNS complications associated with diabetes.
• The administration of aldose reductase inhibitors as adjuvant therapy along with standard antidiabetic medication is recommended as they may slow the progression of diabetic CNS complications. Further clinical studies are needed to confirm this new strategy.