Page 55 - AN-3-2

Advanced Neurology Inflammation in diabetic stroke: Pathogenesis

Figure 2. Schematic diagram depicting the inflammation cascade in ischemic brain injury starting from macroglia reaction (left), under the influence of
diabetes (denoted in red)
Abbreviations: BBB: Blood-brain barrier; DAMP: Danger-associated molecule patterns; IL: Interleukin; NF-κB: Nuclear factor kappa B;
TLR: Toll-like receptors.

IL-10. 38,39 It is a dynamic gradual transition, which is not 5. Inflammation exacerbates ischemic
fully clarified. It may be affected by the severity of tissue stroke in diabetes
damage and its surrounding inflammatory conditions.
Type 2 diabetes is associated with a chronic low-grade
Autophagy is a dynamic process of self-degradation systemic inflammation evidenced by elevated NF-κB
of intracellular components and can be activated by and circulating inflammatory cytokines, increased
nutrient deficiency and metabolic stress. It is essential proinflammatory immune cells, and oxidative stress. 32,37,47,53
for maintaining homeostasis. During ischemic stroke,
50
inflammation directly triggers autophagy. Autophagy can During acute ischemic stroke, hyperglycemia further
51
play a dual role in ischemia: On the one hand, autophagy promotes inflammation by inducing overexpression of
removes damaged mitochondria and reduces oxidative proinflammatory cytokines and adhesion molecules via the
stress. Moderate autophagy weakens neuroinflammation activation of NF-κB, resulting in bigger-extent leukocyte
by inhibiting the activation of inflammasomes and infiltration, which damages the brain tissue. IL-1β is the
regulating the phenotype transformation of microglia. 51,52 hallmark of macrophage/microglia and other immune
On the other hand, excessive autophagy exacerbates brain cell activation. IL-1β level is significantly higher in the
54
injury. 52 diabetic ischemic brain. Corticosterone release during
an ischemic episode inhibits the binding of insulin to its
Inflammation during acute ischemic stroke is a complex
process, starting with microglial activation minutes after receptor, leading to metabolic changes in diabetic patients
(e.g., lactic acidosis), which can trigger more severe
ischemic insult, followed by the recruitment of peripheral inflammation. A study has shown that dysregulation
55
inflammation cells into the ischemic region. The and persistent pro-inflammatory macrophage (M1
inflammatory microenvironment has a significant influence phase) polarization contribute to poor wound healing in
on microglial/macrophage phenotype. Interacting with diabetic individuals. It is yet to be established whether
56
autophagy, inflammation can be seen as a double-edged in individuals with diabetes, the activated macrophages
sword, playing both a neurotoxic and neuroprotective role
in ischemic brain damage, depending on the timing and and infiltrating inflammatory cells in the ischemic brain
the surrounding conditions, cell type involved and their also assume a persisted pro-inflammatory M1 phenotype,
resulting in prolonged and excessive inflammation.
phenotypes (e.g., M1 vs. M2). The complex temporospatial
sequences of evolving inflammation in the ischemic Hyperglycemia causes mitochondrial superoxide
brain damage are not fully understood. Furthermore, overproduction, which can activate the formation of
these processes can present as even more complicated in AGE and protein kinase C (PKC) signaling, worsening
diabetes. inflammation during ischemia. Chronic hyperglycemia

Volume 3 Issue 2 (2024) 5 doi: 10.36922/an.1683