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Advanced Neurology Inflammation in diabetic stroke: Treatment target

preclinical studies, whereas most stroke patients have diabetic stroke is very limited. There is also a paucity
multiple comorbidities, such as hypertension, diabetes, of randomized trials examining the impact of higher
and hyperlipidemia. It is well established that stroke levels of physical activity on cardiovascular events.
outcomes are worse in patients with comorbidities. Even Conventionally, practicing a healthy lifestyle and
in studies using special disease models, such as db/db maintaining good glycemic control may help reduce
type 2 diabetic mice, experiments were undertaken when inflammation in diabetes and lessen cardiovascular risk
they were at young age, long before the manifestation in diabetic individuals. Emerging evidence indicates
of diabetes-related complications. Hence, preclinical that gut microbiota may play a possible role in stroke
researchers should consider age, sex, and comorbidities pathogenesis especially in diabetic individuals;
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while using preclinical models to more closely replicate the therefore, modulation of the gut microbiota could
clinical conditions to reduce the gaps between preclinical therefore provide a novel therapeutic strategy.
studies and clinical trials. Third, different ischemic models, The key consequence of hyperglycemia is the generation
transient versus permanent and focal versus global, and of AGEs, which induce RAGE in macroglia/macrophages.
the duration of ischemia may result in different degrees AGE-RAGE interaction represents a crucial step in
of brain damage, triggering different inflammatory initiating inflammation. It has been shown that AGEs
responses. This could be a potential explanation for some and RAGE are highly expressed in human diabetic
of the conflicting results. We propose customization of the atherosclerosis. Soluble form of RAGE is claimed to be
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various treatment approaches based on stroke severity and able to block proinflammatory activities induced by AGE-
whether successful reperfusion has been achieved. Fourth, RAGE interactions. However, whether soluble RAGEs can
the treatment window showing efficacy in preclinical facilitate AGE clearance to quell AGE-associated immune/
research may not be applicable to clinical trials. Oftentimes, inflammatory and pro-oxidative responses remains largely
drug administration was conducted a long time after the unknown. 118
occurrence of ischemia in clinical trials than in preclinical
studies. In addition, some neuroprotective treatments, such Single molecules are commonly touted as potential
as antioxidants, may need to be repeated to ensure clinical therapeutics for inflammation, but burgeoning findings
effectiveness. In another aspect, outcome measurements in have shown that cell-based therapies, such as neural
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preclinical studies may not be suitable for use in clinical stem cells and activated MSCs, hold promise in
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trials. For instance, reduced infarct size is employed as modulating inflammation. Stem cells stimulate endogenous
an outcome variable in many animal studies, but such neurogenesis, but it should be noted that their survival
variable is not a sensitive imaging parameter in clinical can be hindered in the pathologic environment created
trials. Furthermore, behavioral outcome measurements after ischemic stroke, especially under the overwhelming
used in preclinical studies may not adequately reflect the inflammatory conditions. A prominent advantage of
complex interaction of cognitive functional and behavioral cell-based therapies is that they could potentially deliver
symptoms in humans, especially those with secondary multiple therapeutic molecules in appropriate amounts to
neurodegeneration. Although immunomodulation the target sites as per the injury status, thereby promoting
therapy has shown to be effective in preclinical studies, repair to achieve better functional recovery. To date, there
such efficacy is not translatable in clinical trial settings, and are no studies reporting the utilization of stem cells to treat
the risk of infection and conventional stroke risk factors stroke patients with diabetes.
may counteract the beneficial effect. In addition, given the
complex pathophysiological processes of stroke in elderly 6. Conclusion
stroke patients with comorbidities, this therapy may not be Diabetes is a metabolic disease which is associated with
potent enough to make a significant difference in clinical inflammatory and immunological processes. Ischemic
setting. Therefore, combining immunomodulation therapy stroke triggers highly intricate spatiotemporal inflammatory
with other mechanism such as edaravone which has anti- pathways, presenting even more complexities in
oxidative effect; and dexborneol with anti-inflammatory individuals with diabetes. A more complete time-sensitive
effect (TASTE trial) should be attempted in future studies understanding of post-stroke inflammation mechanisms
to strengthen therapeutic efficacy. in diabetes is essential for developing appropriate therapies
Inflammation plays an important role in stroke and that target inflammation and complement reperfusion
post-ischemic brain damage especially in individuals therapy to achieve better outcomes in diabetic stroke.
with diabetes. In this review, we provide an overview on Acknowledgments
neuroinflammation and immunomodulation therapies
in ischemic stroke, but related evidence concerning None.

Volume 3 Issue 2 (2024) 8 doi: 10.36922/an.1694