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Advanced Neurology Inflammation in diabetic stroke: Treatment target

improve functional outcomes at 90 days (NCT04734548). as an adjunct therapy for stroke. Studies in diabetic
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Other agents targeting M1 to M2 phenotype transformation stroke patients have shown that alpha lipoic acid, which
are currently being studied in preclinical trials. 74 can activate 5’-AMP-activated protein kinase and inhibit
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Microglial autophagy can regulate phagocytosis and NF-κB, can significantly diminish oxidative stress.
reduce inflammation, hence promoting the M2 phase, Antioxidants are among the most promising therapeutic
but overactivated autophagy may also contribute to class for the treatment of ischemic stroke, but the ideal
neuronal injury. The mechanism of microglial autophagy treatment window is uncertain. Longer treatment windows
in ischemic stroke and its regulation is not fully elucidated. and repeat treatments may be needed.
Furthermore, microglia are dysfunctional in diabetes, Melatonin is a well-known neurohormone secreted by
and the induction and progression of diabetic microglial the pineal gland that regulates the sleep-awake cycle. Recent
autophagy remains to be elucidated. A preclinical study evidence has shown that melatonin is widely distributed
showed that upregulated autophagy exacerbates ischemic in the mitochondria, functioning as a mitochondrial
brain injury in diabetic mice. Regulating microglial antioxidant. A single dose of melatonin given to type 1
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autophagy to the right subtype at the appropriate time diabetic rats 30 min before ischemia resulted in reduced
and under different conditions (e.g., diabetes) serves as infarct volume and milder neurological deficits by stabilizing
a potential treatment strategy to enhance post-ischemia mitochondria and dampening NF-κB activation. Several
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brain repair. clinical trials on melatonin in acute stroke are presently
ongoing (CT03843008, NCT05857046).
3.4. Anti-oxidative stress strategies
Oxidative stress develops following ischemia, contributing 3.5. Remote ischemic conditioning (RIC)
to brain injury. Decreased plasma antioxidant levels have RIC is a procedure in which a sublethal ischemia and
been observed in patients with stroke and are even lower reperfusion are applied to an organ or tissue to trigger
in patients with diabetes. Treatments that inhibit free endogenous protection against tissue injury. The common
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radical production and increase free radical degradation practice in human is to occlude blood flow repetitively in the
have been studied with promising results. Allopurinol, a upper limbs. Preclinical data have shown that RIC amplifies
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xanthine oxidase inhibitor, and NS-398, a cyclooxygenase-2 endogenous neuronal repairing mechanisms, such as
inhibitor, have been shown to be neuroprotective. 83,84 increasing the expression of growth factors (e.g., BDNF
Allopurinol appears to improve cerebral nitric oxide (NO) and IGF-1), promoting arteriogenesis and cerebral blood
activity in individuals with diabetes. However, allopurinol flow, stimulating synaptogenesis, axonal regeneration,
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given within 30 days of acute stroke or TIA did not reduce and remyelination. A preclinical study showed that RIC
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the white matter hyperintensity progression or the risk of reduced CD8 T-cell infiltration and the expression of
stroke (OILO-FIST trial). 86 proinflammatory cytokines including IL-1β and TNF-α in
Free radical scavengers NXY059 and edaravone were diabetic rats, suggesting that RIC in acute ischemia may
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tested in ischemic stroke. 87,88 Clinical trials on NXY-059 attenuate brain injury by modulating inflammation. A
in acute ischemic stroke showed conflicting results. 87,89 meta-analysis of clinical trial confirmed that RIC can lead
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Although SAINT I trial showed a promising result of to improved 90-day functional outcomes. Further, trials
reduced disability at 90 days, the SAINT II trial deemed assessing RIC in combination with reperfusion treatments
NXY-059 ineffective. It has been shown that edaravone are awaited (NCT03152799). However, without a complete
alone could improve neurological symptoms, but the understanding of the time window and effective duration
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effect is of limited significance. Borneol, a naturally of RIC, it is challenging to establish a consistent and
occurring highly lipid soluble bicyclic monoterpene has feasible RIC protocol. 98
anti-inflammatory effects. The compound edaravone Despite the rapid advancements in neuroinflammation
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dexborneol showed synergistic effects in ischemic stroke and immune treatment for acute ischemic stroke, therapy
in a Chinese study, resulting in good functional outcomes options for diabetic stroke still remain scarce.
at 90 days (TASTE trial). However, most studies on
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edaravone were conducted in Asian populations; therefore, 4. Post-stroke treatment targets
similar trials should be expanded to wider populations. Treatments targeting inflammation could be a double-

Ascorbic acid may potentiate NO synthesis in edged sword as suppression of the adaptive immune
endothelial cells, but it can act as a pro-oxidant in certain response increases the risk of post-stroke infection,
circumstances. Until its effect on long-term recovery has particularly in diabetic individuals. Many efforts have been
been established, ascorbic acid cannot be recommended made to prevent and reduce stroke-associated pneumonia

Volume 3 Issue 2 (2024) 6 doi: 10.36922/an.1694