الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
The potential of modulating the post-ischemic immune response by neuroprotective drugs to improve stroke outcome is an interesting approach as it is one of the rare interventions that could be initiated in a delayed fashion and still be expected to have an effect. There are, however, potential dangers of manipulating a response which is so complex and incompletely understood.
Treatments targeting a diverse range of cellular properties have been found to ameliorate tissue damage and improve functional deficits in animal models of stroke.
Therefore in this work, we reviewed the inflammatory response to brain ischemia and the potential role of anti-inflammatories. Also, this study provides depth insights into the complex downstream TLR signalling events following cerebral ischemia. As TLR has been involved in cerebral brain damage in stroke, TLR inhibition or blocking could be a potential therapy to reduce ischemic brain damage. Furthermore, TLRs are a family of receptors whose activation occurs at the starting of inflammatory response and so, their blocking or inhibition could eliminate some inflammatory responses.
Behavioural tests indicate a severe deficit in the neurological function, extensive lesions developed and abrupt increase in neural degeneration in the ischemic animals. Ischemia increased mRNA expression of the TLR and their adaptors, augmented leukocyte antigen CD45, the pro-inflammatory transcription factor NF-κB p65 activity and the levels of different inflammatory mediators TNF-α, IL-1β and IL-6 after the ischemic insult.
Brain ischemia resulted in leukocytes infiltration in brain, contributing to cerebral damage. NF-κB promotes inflammatory gene expression, thus precipitates severe neuronal damage. There is an association between IL-1β up-regulation and the infarct size increment, or bad outcome. IL-6 is a plethoric cytokine with several detrimental effects which contribute to early inflammatory injury in the brain. TNF-α is considered the principal mediator of neuroinflamattion that elicits a cascade of cellular events culminating in neuronal death.
Candesartan have cerebroprotective properties during cerebral ischemia, independent of their blood pressure lowering actions. Candesartan is widely used for the treatment of high blood pressure, management of chronic heart failure, diabetic nephropathy, reverse endothelial dysfunction, renal and cardiovascular injury, prevent cerebrovascular events and attenuate oxidative stress. The neuro-protection and neuro-restorative properties of candesartan occur by separate distinct mechanisms other than hypertension related mechanisms. The present findings may offer an explanation for the observed beneficial actions of ATR1 antagonists in patients and in animal models after brain ischemia.
The result obtained in this study can be summarized as follows; candesartan improved behavioural functions, reduced cerebral infarct size, decreased TLR2, TLR4 and their adaptor protein expression, diminished NF-κB activation with concomitant reduction in key inflammatory mediator production (IL-1β, IL-6 and TNF-α).
In the current study, GL improved neurological scores and the motor activities, attenuated infract volume and neural degeneration, suppressed the mRNA expression of TLR2, TLR4, MyD88, TRIF and IRF-3. Furthermore, GL reduced different inflammatory mediators TNF